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Shift work actigram

CloseShift work actigramShift work actigramThese actigraphic recordings are from a nurse who works the day shift and a nurse who works the night shift. A 24-hour time interval (ranging from 12:00 PM to 12:00 PM) is depicted on the X-axis; sequential dates are depicted on the Y-axis. Note that typical sleep periods (eg, 10:00 PM to 6:00 AM) are in the center of the actigram. The actigram denotes physical activity in black, which correlates with wakefulness. An absence of physical activity correlates with pronounced inactivity and periods of sleep. Periods of sleep (aqua) are determined by the actigraphy software. This actigram also provides light exposure by wavelength, including white, red, green, and blue. In this figure, the day shift nurse appears to go to bed between 11:00 PM and 12:30 AM each night and gets out of bed between 6:00 AM and 7:00 AM each day with the exception of day 3 (Saturday), when they appear to stay in bed until 9:00 AM. In contrast, the night shift nurse has variable sleep-wake periods that correspond to their work schedule. For example, the night shift nurse appears to go to bed between 11:00 PM and 3:00 AM on days 2 to 4 and between 8:00 AM and 8:30 AM on days 5 to 7.Graphic 113942 Version 2.0

Implantable cardioverter-defibrillator (ICD) electrogram anti-tachycardia pacing for monomorphic ventricular tachycardia (VT)

CloseImplantable cardioverter-defibrillator (ICD) electrogram anti-tachycardia pacing for monomorphic ventricular tachycardia (VT)Implantable cardioverter-defibrillator (ICD) electrogram anti-tachycardia pacing for monomorphic ventricular tachycardia (VT)Stored intracardiac electrogram from an ICD showing the development of monomorphic ventricular tachycardia, which is successfully terminated by a burst of anti-tachycardia pacing delivered by the ICD. This tachycardia is monomorphic VT, but is labeled VF by the device because it was detected in the VF zone due to the rapid rate.RA: right atrial; RV: right ventricular; VT: ventricular tachycardia; VF: ventricular fibrillation; ATP: anti-tachycardia pacing; AS: atrium sensed; VS: ventricle sensed.Graphic 114829 Version 2.0

Ventricular tachycardia

CloseVentricular tachycardiaVentricular tachycardiaAn example of concordance/absence of rS complex and initial R wave in AVR.Courtesy of Leonard Ganz, MD.Graphic 129901 Version 1.0

Chlorhexidine gluconate (topical): Pediatric drug information

CloseChlorhexidine gluconate (topical): Pediatric drug informationChlorhexidine gluconate (topical): Pediatric drug information(For additional information see "Chlorhexidine gluconate (topical): Drug information" and see "Chlorhexidine gluconate (topical): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USBetasept Surgical Scrub [OTC];Biopatch Protective Disk/CHG [OTC];Chlorhexidine Gluconate [OTC];Dyna-Hex 2 [OTC];Dyna-Hex 4 [OTC];Hibiclens [OTC];Tegaderm CHG Dressing [OTC]Therapeutic CategoryAntibiotic, Oral Rinse;Antibiotic, TopicalDosing: NeonatalSkin cleanser, proceduralSkin cleanser, procedural (eg, phleobotomy, central line placement [PICC, UAC], line maintenance care): Note: Guidelines for pediatric patients and adults recommend using a >0.5% chlorhexidine preparation in alcohol; however, no recommendations are provided for neonates and infants <2 months (IDSA [O’Grady 2011]). NICU specific recommendations suggest no preferred agent, but advise against using tincture of iodine (AAP [Polin 2012]); most neonatal studies have used a 2% chlorhexidine and alcohol preparation (Chapman 2013; Garland 2009; O’Connor 2016); a few studies have used a 0.5% chlorhexidine concentration (Garland 1995; Garland 1996). It is recommended to use chlorhexidine-containing products with care in this population due to potential risk of dermal irritation or chemical burns.Premature or term neonates with body weight >1.5 kg and PNA >7 days: Limited data available: Topical: Cleanse site with chlorhexidine product for ~30 seconds, allow to dry (~30 to 60 seconds) prior to line insertion, dressing application or lab draw (Chapman 2013; Garland 1995; Garland 2009; O’Connor 2016). Note: Minimal age and weight variable; use has been evaluated in ELBW neonates with GA as young as 24 weeks and birth weight as low as 630 g (Chapman 2013); some studies suggest, however, an increased risk of skin irritation and burns with decreased maturity and bodyweight (AAP [Polin 2010]; Garland 1996; Garland 2009; Tamma 2010); risk versus benefit must be weighed prior to use in neonates.Dosing: PediatricSkin cleanser for preoperative skin preparation, skin wound and general skin cleanser for patientsSkin cleanser for preoperative skin preparation, skin wound and general skin cleanser for patients: Topical:Infants <2 months: Note: It is recommended to use with care in this population due to potential risk of dermal irritation or chemical burns. Expert suggestions are variable depending upon site and clinical scenario. Not all products may be appropriate for use in this population; refer to product specific labeling. Some experience in neonatal patients applicable to this patient population (Garland 2009; Tamma 2010).Preoperative skin preparation: Solution: Apply liberally to surgical site and swab for at least 2 minutes. Dry with sterile towel. Repeat procedure (swab for additional 2 minutes and dry with sterile towel).Wound care and general skin cleansing: Rinse area with water, then apply the minimum amount of chlorhexidine necessary to cover skin or wound area and wash gently. Rinse again thoroughly.Infants ≥2 months, Children, and Adolescents: Topical solution:Preoperative skin preparation: Solution: Apply liberally to surgical site and swab for at least 2 minutes. Dry with sterile towel. Repeat procedure (swab for additional 2 minutes and dry with sterile towel).Wound care and general skin cleansing: Rinse area with water, then apply the minimum amount of chlorhexidine necessary to cover skin or wound area and wash gently. Rinse again thoroughly.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Adult(For additional information see "Chlorhexidine gluconate (topical): Drug information")Note: General dosing guidelines provided; refer to specific product labeling for dosing instructions.AntisepticAntiseptic: Topical:Surgical scrub: Scrub hands and forearms with ~5 mL for 3 minutes paying close attention to nails, cuticles, and interdigital spaces, and rinse thoroughly, wash for an additional 3 minutes with 5 mL, rinse, and dry thoroughly.Health care personnel hand antiseptic: Liquid or solution: Wash with ~5 mL for 15 seconds; rinse thoroughly with water and dryPreoperative skin preparation:Solution: Apply liberally to surgical site and swab for at least 2 minutes. Dry with sterile towel. Repeat procedure (swab for additional 2 minutes and dry with sterile towel).Applicator (ChloraPrep One-Step):Dry surgical sites (eg, abdomen, arm): Completely wet treatment area; use gentle back and forth strokes for ~30 seconds. Allow solution to air dry for ~30 seconds. If using an ignition source (eg, electrocautery), allow solution to completely dry for a minimum of 3 minutes for hairless skin and up to 1 hour in hair; do not blot or wipe away. Note: Prior to use with electrocautery procedures, consult specific product labeling to determine if the ChloraPrep product may be used near an ignition source.Moist surgical sites (eg, inguinal area): Completely wet treatment area; use gentle back and forth strokes for ~2 minutes. Allow solution to air dry for ~ 1 minute. If using an ignition source (eg, electrocautery), allow solution to completely dry for a minimum of 3 minutes for hairless skin and up to 1 hour in hair; do not blot or wipe away. Note: Prior to use with electrocautery procedures, consult specific product labeling to determine if the ChloraPrep product may be used near an ignition source.Wound care and general skin cleansing: Rinse area with water, then apply minimum amount necessary to cover skin or wound area and wash gently. Rinse again thoroughly.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productLiquid, External: Betasept Surgical Scrub: 4% (118 mL, 237 mL, 473 mL, 946 mL)Hibiclens: 4% (15 mL, 118 mL, 236 mL, 473 mL, 946 mL, 3790 mL) [contains fd&c red #40 (allura red ac dye), isopropyl alcohol]Generic: 2% (118 mL [DSC]); 4% (118 mL [DSC], 237 mL [DSC], 473 mL [DSC], 946 mL [DSC], 3800 mL [DSC])Miscellaneous, External: Biopatch Protective Disk/CHG: (Dressing) (10 ea)Tegaderm CHG Dressing: (Dressing) (1 ea)Pad, External: Generic: 2% (2 ea, 6 ea)Solution, External: Chlorhexidine Gluconate: 2% (118 mL) [latex free; contains isopropyl alcohol]Dyna-Hex 2: 2% (473 mL) [contains isopropyl alcohol]Dyna-Hex 4: 4% (118 mL, 473 mL) [contains isopropyl alcohol]Generic Equivalent Available: USMay be product dependentAdministration: PediatricTopical: Keep out of eyes, ears, and mouth. Do not routinely apply to wounds which involve more than superficial layers of skin. Avoid contact with meninges (ie, do not use on lumbar puncture sites). Solutions may be flammable (may contain alcohol); consult specific product labeling to determine if product may be used with electrocautery procedures; if product can be used near an ignition source (eg, cautery, laser), avoid exposure to open flame and/or ignition source until completely dry; avoid application to hairy areas which may significantly delay drying time. When using the ChloraPrep applicator, do not touch sponge. Hold applicator sponge down and pinch wings of applicator once to activate ampul and release antiseptic.Administration: AdultTopical: Keep out of eyes, ears, and mouth. Do not routinely apply to wounds which involve more than superficial layers of skin. Avoid contact with meninges (ie, do not use on lumbar puncture sites). Solutions may be flammable (may contain alcohol); consult specific product labeling to determine if product may be used with electrocautery procedures; if product can be used near an ignition source (eg, cautery, laser), avoid exposure to open flame and/or ignition source until completely dry; avoid application to hairy areas which may significantly delay drying time. When using the ChloraPrep applicator, do not touch sponge. Hold applicator sponge down and pinch wings of applicator once to activate ampul and release antiseptic.Storage/StabilityStore at room temperature. Alcohol-containing topical products are flammable; keep away from flames or fire.UseTopical: Skin cleanser for preoperative skin preparation, prior to injection; skin wound and general skin cleanser for patients (FDA approved in pediatric patients [age not specified] and adults); surgical scrub and antiseptic hand rinse for health care personnel (FDA approved in adults). Note: Indications vary by product; refer to specific product labeling for details.Medication Safety IssuesPediatric patients: High-risk medication:KIDs List: Chlorhexidine, when used in very low birthweight neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of chemical burns (strong recommendation; low quality of evidence) (PPA [Meyers 2020]).Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.Dermatologic: Allergic sensitization, erythema, hypersensitivity reaction, rough skin, xeroderma<1%, postmarketing, and/or case reports: Anaphylaxis (Health Canada May 2016), dyspnea, facial edema, nasal congestionContraindicationsHypersensitivity to chlorhexidine or any component of the formulationWarnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity reactions: Serious allergic reactions, including anaphylaxis, have been reported.Dosage form specific issues:• Topical: For topical use only. Keep out of eyes, ears, and the mouth; if contact occurs, rinse with cold water immediately; permanent eye injury may result if agent enters and remains in the eye. Deafness has been reported following instillation in the middle ear through perforated ear drums. Avoid applying to wounds that involve more than the superficial skin layers. Avoid repeated use as general skin cleansing of large surfaces (unless necessary for condition). Not for preoperative preparation of face or head; avoid contact with meninges (do not use on lumbar puncture sites). Avoid applying to genital areas; generalized allergic reactions, irritation, and sensitivity have been reported. Solutions may be flammable (products may contain alcohol); avoid exposure to open flame and/or ignition source (eg, electrocautery) until completely dry; avoid application to hairy areas which may significantly delay drying time. Use with caution in children <2 months of age due to potential for increased absorption, and risk of irritation or chemical burns. May cause staining of fabrics (brown stain) due to a chemical reaction between chlorhexidine gluconate bound to fabric and chlorine (if sufficient chlorine is present from certain laundry detergents used during laundering process).Other warnings/precautions:• Appropriate use: Topical: When used as a topical antiseptic, improper use may lead to product contamination. Although infrequent, product contamination has been associated with reports of localized and systemic infections. To reduce the risk of infection, ensure antiseptic products are used according to the labeled instructions; avoid diluting products after opening; and apply single-use containers only one time to one patient and discard any unused solution (FDA Drug Safety Communication 2013).Warnings: Additional Pediatric ConsiderationsAlthough topical chlorhexidine is widely used in many NICUs as a skin cleanser prior to procedures (eg, central venous line placement/care) (Tamma 2010), data is lacking to support use in premature infants. Manufacturer's labeling recommends using with caution in premature neonates and infants <2 months of age as chlorhexidine-containing products may cause irritation or chemical burns. A survey of US NICU chlorhexidine use reports dermal burns occurring more frequently in neonates with birth weight <1,500 g (Tamma 2010). If used for neonatal dermal site cleansing, some suggest using sterile water or normal saline to remove excess disinfectant after procedures may help avoid chemical burns (Eichenwald 2017; Nuntnarumit 2013). Several studies have noted detectable serum concentrations in neonates after chlorhexidine exposure; no correlation between serum concentration and GA, birth weight, or PNA was identified; the clinical significance is undetermined (Chapman 2013; Garland 2009).Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programThere are no known significant interactions.Pregnancy ConsiderationsNo reports of adverse effects in newborns have been reported, even though chlorhexidine is commonly used during labor and in the neonate. Moreover, only very small amounts of disinfectant reach the maternal circulation and the fetus.Monitoring ParametersTopical: Monitor for redness/skin irritation especially in infants <2 monthsMechanism of ActionChlorhexidine has activity against gram-positive and gram-negative organisms, facultative anaerobes, aerobes, and yeast; it is both bacteriostatic and bactericidal, depending on its concentration. The bactericidal effect of chlorhexidine is a result of the binding of this cationic molecule to negatively charged bacterial cell walls and extramicrobial complexes. At low concentrations, this causes an alteration of bacterial cell osmotic equilibrium and leakage of potassium and phosphorous resulting in a bacteriostatic effect. At high concentrations of chlorhexidine, the cytoplasmic contents of the bacterial cell precipitate and result in cell death.Pharmaco*kinetics (Adult data unless noted)Absorption: Topical: Neonates: Detectable serum concentrations have been noted following topical chlorhexidine administration (Chapman 2013; Cowen 1979; Garland 2009)Pricing: USLiquid (Betasept Surgical Scrub External)4% (per mL): $0.02Liquid (Hibiclens External)4% (per mL): $0.03Misc (Biopatch Protective Disk/CHG External)(Dressing) (per each): $8.83Misc (Tegaderm CHG Dressing External)(Dressing) (per each): $10.01Solution (Dyna-Hex 2 External)2% (per mL): $0.01Solution (Dyna-Hex 4 External)4% (per mL): $0.04Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAcriflex (GB);Alospray (PT);Amident (RU);Asseptic (BR);Biorgasept (FR);Cedium (HK);Cetavlex (FR);Chlorhex (TH);Chlorohex (SG);Clorosan (IT);Clorxil (ES);Descutan (SE);Dettol Sterilon (NL);Diaseptyl (FR);Dosiseptine (CH);Eczmol/Cetraben Protect Antimicrobial Cream (MT);Handscrub (PT);Hexene Skin Cleanser (TH);Hexicon (RU);Hexiscrub (BD);Hexisol (BD);Hexitane (BD);Hexoscrub (SG);Hibidil (FR);Hibiscrub (BE, CH, ES, FR, GB, IE, KW, LU, MT, NL, NO, SA, SE, SG);Hibitane (BE, DK, FR, IS, KW, MT, PT, SA);Hydrex (HK, IE, TH);Klorhexol (FI);Lifo-Scrub (GR);LirahexidineTopical (EC);Marclorhex (BR);Mediscrub (ID);Microshield (AU, KR, SG);Neoxene (IT);Neoxinal (IT);Normosept (ES);Scanlin (HK);Scrubing S 4% Soln (KR);Septadine Scrub (IL);Septal (IL);Septalone (IL);Sterets Unisept (IE);Unisept (GB);Vitawund (AT)For country code abbreviations (show table)American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. [PubMed 9024461]Chapman AK, Aucott SW, Gilmore MM, Advani S, Clarke W, Milstone AM. Absorption and tolerability of aqueous chlorhexidine gluconate used for skin antisepsis prior to catheter insertion in preterm neonates. J Perinatol. 2013;33(10):768-771. [PubMed 23702618]ChloraPrep One-Step 10.6 mL (chlorhexidine) [prescribing information]. Leawood, KS: CareFusion; November 2013.ChloraPrep One-Step 3 mL (chlorhexidine) [prescribing information]. Leawood, KS: CareFusion; November 2013.Cowen J, Ellis SH, McAinsh J. Absorption of chlorhexidine from the intact skin of newborn infants. Arch Dis Child. 1979;54(5):379-383. [PubMed 475414]de la Rosa M, Sturzenberger OP, Moore DJ. The use of chlorhexidine in the management of gingivitis in children. J Periodontol. 1988;59(6):387-389. [PubMed 3164781]Food and Drug Administration. FDA Drug Safety Communication: FDA requests label changes and single-use packaging for some over-the-counter topical antiseptic products to decrease risk of infection. http://www.fda.gov/Drugs/DrugSafety/ucm374711.htm. Updated November 20, 2013. Accessed October 1, 2014.Garland JS, Alex CP, Mueller CD, Cisler-Kahill LA. Local reactions to a chlorhexidine gluconate-impregnated antimicrobial dressing in very low birth weight infants. Pediatr Infect Dis J. 1996;15(10):912-914. [PubMed 8895928]Garland JS, Alex CP, Uhing MR, Peterside IE, Rentz A, Harris MC. Pilot trial to compare tolerance of chlorhexidine gluconate to povidone-iodine antisepsis for central venous catheter placement in neonates. J Perinatol. 2009;29(12):808-813. [PubMed 19812587]Garland JS, Buck RK, Maloney P, et al. Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates: a prospective trial. Pediatr Infect Dis J. 1995;14(6):510-516. [PubMed 7667056]Greenstein G, Berman C, and Jaffin R, “Chlorhexidine. An Adjunct to Periodontal Therapy,” J Periodontol, 1986, 57(6):370-7. [PubMed 3522851]Healthy Canadians Recall & Alerts. Summary safety review − topical antiseptic non-prescription chlorhexidine products − assessing the potential risk of serious allergic reactions (hypersensitivity reactions). Available at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/chlorhexidine-eng.php. Published May 13, 2016. Accessed May 17, 2016.Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]O'Connor C, Philip RK, Powell J, et al. Combined education and skin antisepsis intervention for persistently high blood-culture contamination rates in neonatal intensive care. J Hosp Infect. 2016;93(1):105-107. [PubMed 26944902]O'Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011;52(9):e162-193. [PubMed 21460264]PerioGard (chlorhexidine gluconate) [prescribing information]. New York, NY: Colgate Oral Pharmaceuticals; July 2015.Polin RA, Denson S, Brady MT, Committee on Fetus and Newborn, Committee on Infectious Diseases. Strategies for prevention of health care-associated infections in the NICU. Pediatrics. 2012;129(4):e1085-1093. [PubMed 22451712]Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]Tamma PD, Aucott SW, Milstone AM. Chlorhexidine use in the neonatal intensive care unit: results from a national survey. Infect Control Hosp Epidemiol. 2010;31(8):846-849. [PubMed 20586654]Yong D, Parker FC, and Foran SM, “Severe Allergic Reactions and Intra-Urethral Chlorhexidine Gluconate,” Med J Aust, 1995, 162(5):257-8. [PubMed 7891607]Topic 115977 Version 89.0

Chlorhexidine gluconate (topical): Drug information

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Search "وام بلوبانک 75 میلیونی"

CloseFollitropin beta (recombinant human follicle stimulating hormone): Drug informationFollitropin beta (recombinant human follicle stimulating hormone): Drug information(For additional information see "Follitropin beta (recombinant human follicle stimulating hormone): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USFollistim AQBrand Names: CanadaPuregonPharmacologic CategoryGonadotropin;Ovulation StimulatorDosing: AdultNote: Dose should be individualized. Use the lowest effective dose. Over the course of treatment, doses may vary depending on individual patient response. Doses may need adjustment when changing between products and/or methods of administration.Ovulation induction, anovulatory patientsOvulation induction, anovulatory patients:Follistim AQ Cartridge: SUBQ: Stepwise approach: Initiate therapy with 50 units per day for at least the first 7 days. Increase dose by 25 or 50 units at weekly intervals until follicular growth and/or estradiol levels indicate an adequate ovarian response. Adjust dose to prevent multiple follicular growth and cycle cancellation. Continue treatment until ultrasonic visualizations and/or serum estradiol determinations approximate the preovulatory conditions based on follicular development. Maximum (individualized) daily dose: 250 units. If response to follitropin is appropriate, human chorionic gonadotropin (hCG) is given 1 day following the last dose to induce final oocyte maturation and ovulation. Follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS). See "Follitropin Beta Dosing Conversion table" for dosage adjustment between the pen and the cartridge.Puregon (vials) [Canadian product] (IM, SUBQ), Puregon Cartridge [Canadian product] (SUBQ): Stepwise approach: Initiate therapy with 50 units per day for at least the first 7 days. Increase dose gradually until follicular growth and/or plasma estradiol levels indicate an adequate response (daily increase of estradiol levels of 40% to 100% is considered optimal). If response to follitropin is appropriate, hCG is given 1 day following the last dose to induce final oocyte maturation and ovulation. Decrease hCG dose if the number of responding follicles is too high or estradiol levels increase too rapidly (eg, greater than daily doubling for estradiol for 2 or 3 consecutive days); withhold hCG if the ovaries are abnormally enlarged or if abdominal pain occurs. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.Controlled ovarian stimulation, ovulatory patientsControlled ovarian stimulation, ovulatory patients:Follistim AQ Cartridge: SUBQ: Stepwise approach: A starting dose of 200 units is recommended for at least the first 7 days of treatment. Adjust dose up or down for the individual patient based upon ovarian response. Maximum daily dose: 500 units. When a sufficient number of follicles of adequate size are present, dosing of follitropin beta is stopped and the final maturation of the follicles is induced by administering hCG. Oocyte retrieval is performed 34 to 36 hours later. Follow current clinical practice to reduce the risk of OHSS. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.Puregon vials [Canadian product] (IM, SUBQ), Puregon Cartridge [Canadian product] (SUBQ): A starting dose of 150 to 225 units is recommended for at least the first 4 days of treatment. Adjust dose for the individual patient based upon ovarian response. Maximum daily dose: 450 units (limited experience with higher doses). When a sufficient number of follicles of adequate size are present, the final maturation of the follicles is induced by administering hCG 30 to 40 hours after the last follitropin beta dose. Withhold hCG in cases where the ovaries are abnormally enlarged on the last day of follitropin beta therapy. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.Spermatogenesis inductionSpermatogenesis induction: Note: Pretreatment with hCG monotherapy is required prior to concomitant therapy with follitropin beta and hCG. Follitropin beta therapy may be initiated after normal serum testosterone levels have been reached.Follistim AQ Cartridge, Puregon (vials) [Canadian product], Puregon Cartridge [Canadian product]: SUBQ: 450 units/week (administered as 225 units twice weekly or 150 units 3 times/weekly). Combination therapy with follitropin beta and hCG should be continued for at least 3 to 4 months before any improvement in spermatogenesis can be expected. If no response is noted after this period, combination therapy may be continued. Treatment response has been noted at up to 12 months. See "Follitropin Beta Dosing Conversion table"for dosage adjustment between the pen and the cartridge.Follitropin Beta Dosing Conversion Among Formulationsaa Values listed are rounded to the nearest 25 unit increment.The follitropin beta cartridge contains a prefilled solution that is administered via a pen injector device; it delivers on average an 18% higher amount of follitropin beta when compared to lyophilized and reconstituted follitropin beta delivered using a conventional syringe and needle.If the above starting doses were previously used when administering lyophilized follitropin beta via a conventional syringe, lower starting and maintenance doses should be considered when switching to the follitropin pen with cartridge.The following dose conversion may be used:Dose Administered Using Powder for Solution/Conventional SyringeDose Administered Using Pen75 units50 units150 units125 units225 units175 units300 units250 units375 units300 units450 units375 unitsDosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Subcutaneous: Follistim AQ: 300 units/0.36 mL (0.42 mL); 600 units/0.72 mL (0.78 mL); 900 units/1.08 mL (1.17 mL) [contains benzyl alcohol]Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productSolution, Injection: Puregon: 50 units/0.5 mL ([DSC]); 100 units/0.5 mL ([DSC])Solution, Subcutaneous: Puregon: 300 units/0.36 mL (0.36 mL) [contains benzyl alcohol]Administration: AdultSUBQ: Follistim AQ Cartridge, Puregon Cartridge (Canadian product): Administer by SUBQ injection only, using the Follistim Pen or the Puregon Pen, which can be set to deliver the appropriate dose. Allow to reach room temperature prior to administration to avoid discomfort. Injection may be given in the abdomen just below the navel or upper outer area of thigh. Avoid areas that are tender, red, bruised, or hard.IM, SUBQ: Puregon (Canadian product): Vials: Administer by IM or SUBQ injection. IM injection may be given in the upper outer quadrant of the buttock. IM administration has not been evaluated in males.Use: Labeled IndicationsControlled ovarian stimulation, ovulatory patients: Induction of pregnancy in normal ovulatory patients undergoing controlled ovarian stimulation as part of in vitro fertilization or intracytoplasmic sperm injection.Limitations of use: Prior to therapy, perform a complete gynecologic exam and endocrinologic evaluation to diagnose the cause of infertility; exclude the possibility of pregnancy; evaluate the fertility status of the partner.Ovulation induction, anovulatory patients: Induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure.Limitations of use: Prior to therapy, perform a complete gynecologic exam and endocrinologic evaluation; exclude the possibility of pregnancy; evaluate the fertility status of the partner; exclude a diagnosis of primary ovarian failure; confirm tubal patency.Spermatogenesis induction: Induction of spermatogenesis in patients with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.Limitations of use: Prior to therapy, perform a complete medical exam and endocrinologic evaluation; confirm hypogonadotropic hypogonadism and exclude primary testicular failure; normalize serum testosterone levels with human chorionic gonadotropin; evaluate the fertility status of the partner.Medication Safety IssuesHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency may vary based on indication.1% to 10%:Central nervous system: Headache (7%), fatigue (2%)Dermatologic: Acne vulgaris (7%), skin rash (3%)Endocrine & metabolic: Ovarian hyperstimulation (6% to 8%), gynecomastia (3%), ovarian cyst (3%)Gastrointestinal: Nausea (4%), abdominal distress (3%), abdominal pain (3%), lower abdominal pain (3%)Genitourinary: Pelvic symptoms (discomfort: 8%), pelvic pain (6%)Local: Injection site reaction (7%), pain at injection site (7%)Miscellaneous: Cyst (dermoid: 3%)Postmarketing: Abdominal distention, breast tenderness, constipation, diarrhea, ovarian neoplasm, ovarian torsion, ovary enlargement, spontaneous abortion, thromboembolism, uterine hemorrhage, vagin*l hemorrhageContraindicationsHypersensitivity to recombinant human follicle-stimulating hormone (FSH) products, streptomycin, neomycin, or any component of the formulation; high levels of FSH indicating primary gonadal failure; uncontrolled nongonadal endocrinopathies (eg, adrenal, pituitary, or thyroid disorders); tumor of the ovary, breast, uterus, testis, hypothalamus, or pituitary gland; heavy or abnormal vagin*l bleeding of undetermined origin; ovarian cysts or enlargement not due to polycystic ovary syndrome; pregnancy.Canadian labeling: Additional contraindications (not in the US labeling): Lactation; conditions incompatible with pregnancy (eg, malformation of reproductive organs, uterine fibroid tumors); use in children.Warnings/PrecautionsConcerns related to adverse effects:• Ovarian enlargement: The lowest effective dose should be used to decrease the risk of abnormal ovarian enlargement. If ovaries are abnormally enlarged on the last day of follitropin beta treatment, follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS).• Ovarian hyperstimulation syndrome: OHSS is a rare, exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of human chorionic gonadotropin treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. Decreased CrCl, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; Shmorgun 2017).• Ovarian torsion: Has been reported following gonadotropin treatment; may be related to OHSS, prior ovarian torsion, prior or current ovarian cyst, polycystic ovaries, pregnancy, or prior abdominal surgery. Early diagnosis and prompt detorsion may limit the extent of ovarian damage.• Pulmonary effects: Serious pulmonary conditions, including acute respiratory distress syndrome, have been reported.• Thromboembolic events: In association with and separate from OHSS, thromboembolic events have been reported. Risk may be increased in patients with a personal or family history of thromboembolic events, severe obesity, or thrombophilia.Dosage form specific issues:• Multiple dose injection pens: According to the Centers for Disease Control and Prevention, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: To minimize risks, use only at the lowest effective dose. Monitor ovarian response with transvagin*l ultrasound; concurrent measurement of estradiol levels may also be useful.• Experienced physician: These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management.• Multiple births: May result from the use of these medications; advise patient of the potential risk of multiple births before starting the treatment.Metabolism/Transport EffectsNone known.Drug InteractionsThere are no known significant interactions.Reproductive ConsiderationsFollitropin beta is used for ovulation induction or spermatogenesis induction in couples planning a pregnancy; the fertility status of both partners should be evaluated prior to therapy.Pregnancy ConsiderationsEctopic pregnancies, congenital abnormalities, and multiple births have been reported. The incidence of congenital abnormality may be slightly higher after in vitro fertilization or intracytoplasmic sperm injection than with spontaneous conception; higher incidence may be related to parenteral characteristics (maternal age, sperm characteristics).Follitropin beta is used for the induction of ovulation; use is contraindicated in patients who are already pregnant.Breastfeeding ConsiderationsIt is not known if follitropin beta is present in breast milk.Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made whether to discontinue breastfeeding or the drug, considering the importance of treatment to the mother.Monitoring ParametersOvulation induction: Monitor follicular growth by transvagin*l ultrasound along with concurrent measurement of estradiol levels to determine adequate ovarian response and timing of human chorionic gonadotrophin (hCG) administration.Monitor for signs and symptoms of ovarian hyperstimulation syndrome (OHSS) for at least 2 weeks following hCG administration. Initial symptoms of moderate to severe OHSS may include a sensation of bloating, abdominal pain, rapid weight gain, and decreased urine output (Shmorgun 2017).OHSS: Monitoring of hospitalized patients should include albumin, degree of ascites, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, signs of thromboembolism, vital signs, weight (all daily or as necessary), and liver enzymes (weekly) (Shmorgun 2017).Spermatogenesis: Monitor for sufficient spermatogenesis. This can be directly estimated by sem*n analysis, or indirectly estimated by serum testosterone level. sem*n analysis is recommended 4 to 6 months after starting treatment (Puregon Canadian product monograph).Mechanism of ActionFollitropin beta is a human follicle-stimulating hormone (FSH) preparation of recombinant DNA origin. Follitropins stimulate ovarian follicular growth in patients who do not have primary ovarian failure and stimulate spermatogenesis in patients with hypogonadotropic hypogonadism. FSH is required for normal follicular growth, maturation, gonadal steroid production, and spermatogenesis.Pharmaco*kineticsNote: Data are presented from studies conducted by the manufacturer in pituitary suppressed but otherwise healthy females following SUBQ injection. Pharmaco*kinetic studies were not conducted in males.Absorption: ~78%.Distribution: IV: 8 L.Half-life elimination: ~33 hours.Time to peak: 13 hours.Pricing: USSolution (Follistim AQ Subcutaneous)300 units/0.36 mL (per 0.42 mL): $1,044.00600 units (per 0.78 mL): $2,088.00900 units/1.08 mL (per mL): $2,676.92Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalFollistim (JP);Puregon (AE, AR, AT, BE, BH, BR, CH, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EC, EG, ES, FR, GB, GR, GT, HK, HN, HR, ID, IE, IL, IS, IT, JO, KR, KW, LB, LT, LU, LV, MT, MX, MY, NI, NL, NO, PA, PE, PH, PK, PL, PT, QA, RO, SA, SE, SG, SI, SK, SV, TH, TR, UA, VE, VN);Recagon (LK)For country code abbreviations (show table)Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Corbett S, Shmorgun D, Claman P, et al; Reproductive Endocrinology Infertility Committee. The prevention of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2014;36(11):1024-1033. doi: 10.1016/S1701-2163(15)30417-5. [PubMed 25574681]Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment. Reprod Biol Endocrinol. 2012;10:32. doi: 10.1186/1477-7827-10-32. [PubMed 22531097]Follistim AQ Cartridge (follitropin beta) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; June 2020.Petak SM, Nankin HR, Spark RF, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients -- 2002 Update. Endocr Pract. 2002;8(6):440-456. [PubMed 15260010]Practice Committee of the American Society for Reproductive Medicine (ASRM). Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634-1647. doi: 10.1016/j.fertnstert.2016.08.048. [PubMed 27678032]Puregon (follitropin beta) [product monograph]. Kirkland, Quebec, Canada: Organon Canada Inc; March 2021.Shmorgun D, Claman P. No-268-the diagnosis and management of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2017;39(11):e479-e486. doi: 10.1016/j.jogc.2017.09.003. [PubMed 29080733]Topic 8945 Version 153.0

Alirocumab: Drug information

CloseAlirocumab: Drug informationAlirocumab: Drug information(For additional information see "Alirocumab: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USPraluentBrand Names: CanadaPraluentPharmacologic CategoryAntilipemic Agent, PCSK9 Inhibitor;Monoclonal AntibodyDosing: AdultNote: Use may be considered in patients who do not meet cholesterol treatment goals with dietary modification and other lipid-lowering therapies (ie, maximally tolerated statin plus ezetimibe) (AHA/ACC [Grundy 2018]).hom*ozygous familial hypercholesterolemiahom*ozygous familial hypercholesterolemia: SUBQ: 150 mg once every 2 weeks.Hyperlipidemia, primaryHyperlipidemia, primary: SUBQ: Initial: 75 mg once every 2 weeks or 300 mg once every 4 weeks; for both regimens, if an adequate low-density lipoprotein cholesterol (LDL-C) response is not achieved, may increase or modify dosing regimen to a maximum of 150 mg every 2 weeks.Heterozygous familial hypercholesterolemia undergoing LDL apheresis: SUBQ: 150 mg once every 2 weeks.Secondary prevention of cardiovascular eventsSecondary prevention of cardiovascular events: SUBQ: Initial: 75 mg once every 2 weeks or 300 mg once every 4 weeks; for both regimens, if an adequate LDL-C response is not achieved, may increase or modify dosing regimen to a maximum dose of 150 mg every 2 weeks.Switching regimens: When switching from the monthly regimen to an every-2-week regimen, start the new dose on the next scheduled dosing date; reassess LDL-C 4 to 8 weeks after dosing change.Missed dose: If a dose is missed ≤7 days from the usual day of administration, administer the dose as soon as possible and then resume the original schedule; otherwise, if beyond 7 days, skip the missed dose and resume the normal dosing schedule, or if dosage is monthly, start a new schedule based on this date.Dosing: Kidney Impairment: AdultMild to moderate impairment: No dosage adjustment necessary.Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.Dosing: Hepatic Impairment: AdultMild to moderate impairment: No dosage adjustment necessary.Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Auto-injector, Subcutaneous: Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]Solution Auto-injector, Subcutaneous [preservative free]: Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productSolution Auto-injector, Subcutaneous: Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]Solution Prefilled Syringe, Subcutaneous: Praluent: 75 mg/mL ([DSC]); 150 mg/mL ([DSC]) [contains mouse (murine) and/or hamster protein]Prescribing and Access RestrictionsOnly available via specialty pharmacies. Call 844-772-5836 or visit https://www.praluenthcp.com/support for additional information.Administration: AdultSUBQ: Allow solution to come to room temperature for 30 to 40 minutes prior to administration; do not warm in any other way. Do not shake. Administer by SUBQ injection into the thigh, abdomen (avoiding the 2-inch area around the navel), or upper arm; rotate injection site with each injection; may take up to 20 seconds for full dose to be injected. For the 300 mg dose, administer two 150 mg injections consecutively at 2 different injection sites. Do not inject into skin that is tender, bruised, hard, red hot or damaged, or has visible veins, scars, or stretch marks. Do not coadminister with other injectable drugs at the same injection site. Do not reuse prefilled pens/syringes; single use only. Do not administer if window on pen/syringe is solid yellow (indicates pen/syringe has been used). Do not use prefilled syringe if blue cap is missing or loose, if it has been dropped, or if damaged; avoid touching yellow safety cover. For patients undergoing LDL apheresis, may be administered without regard to the timing of apheresis.Use: Labeled Indicationshom*ozygous familial hypercholesterolemia: Adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies in adults with hom*ozygous familial hypercholesterolemia to reduce LDL-C.Hyperlipidemia, primary: Adjunct to diet, alone or in combination with other LDL-C lowering therapies in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-C.Secondary prevention of cardiovascular events: To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease (Schwartz 2018).Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%: Local: Injection site reaction (4% to 17%, including erythema at injection site, injection site pruritus, pain at injection site, swelling at injection site, tenderness at injection site)1% to 10%:Gastrointestinal: Diarrhea (5%)Hepatic: Increased serum transaminases (>3 x ULN: 2%), liver enzyme disorder (3%)Hypersensitivity: Hypersensitivity reaction (9%, including nummular eczema and hypersensitivity angiitis)Immunologic: Antibody development (6%; neutralizing: <1%)Infection: Influenza (6%)Neuromuscular & skeletal: Muscle spasm (3%), myalgia (4% to 6%)Respiratory: Cough (3%)Postmarketing:Hypersensitivity: AngioedemaRespiratory: Flu-like symptomsContraindicationsSerious hypersensitivity to alirocumab or any component of the formulation.Documentation of allergenic cross-reactivity for PCSK9 inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Warnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity reactions: Hypersensitivity reactions, including some severe reactions requiring hospitalization (eg, hypersensitivity vasculitis, angioedema), have been reported. Discontinue treatment and initiate supportive treatment in patients who develop serious allergic reaction. Other hypersensitivity reactions, including pruritus, rash, and urticaria, have been reported.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapyPregnancy ConsiderationsAlirocumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).Data collection to monitor pregnancy and infant outcomes following exposure to alirocumab is ongoing. Health care providers are encouraged to report exposures of alirocumab during pregnancy (1-844-734-6643).Breastfeeding ConsiderationsIt is not known if alirocumab is present in breast milk; however, IgG molecules are known to be present in breast milk.Serum concentrations to a breastfeeding infant are not expected to be substantial. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the breastfed infant, and the benefits of treatment to the mother.Monitoring ParametersLipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter (AHA/ACC [Grundy 2018]). For patients receiving 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose (LDL-C varies considerably between doses with this regimen). Monitor for hypersensitivity reactions.Reference RangeTreatment goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.Mechanism of ActionAlirocumab is a human monoclonal antibody (IgG1isotype) that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptors (LDLR) on hepatocyte surfaces to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; therefore, the decrease in LDLR levels by PCSK9 results in higher blood levels of LDL-C. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.Pharmaco*kineticsOnset: Peak effect: Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 to 8 hours.Distribution: IV: Vd: ~0.04 to 0.05 L/kg.Metabolism: Expected to undergo proteolysis and be degraded to small peptides and amino acids.Bioavailability: SUBQ: ~85%.Half-life elimination: SUBQ: Steady-state: 17 to 20 days; reduced to 12 days when administered with a statin.Time to peak: SUBQ: 3 to 7 days.Pricing: USSolution Auto-injector (Praluent Subcutaneous)75 mg/mL (per mL): $270.00150 mg/mL (per mL): $286.45Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalPraluent (AT, AU, BE, CH, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HK, HR, IE, IL, IS, JP, KW, LB, LT, MX, MY, NL, NO, PL, PT, RO, SE, SG, SI, TW)For country code abbreviations (show table)Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol [published online November 10, 2018]. Circulation. 2018. doi: 10.1161/CIR.0000000000000625. [PubMed 30586774]Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. 2015;9(2):129-169. doi: 10.1016/j.jacl.2015.02.003. [PubMed 25911072]Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87. doi: 10.4158/EP171764.APPGL. [PubMed 28437620]Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906-915.Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. [PubMed 22235228]Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344.Praluent (alirocumab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; April 2021.Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499. [PubMed 25773378]Rosenson RS. Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 1, 2021.Roth EM, Taskinen MR, Ginsberg HN, et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol. 2014;176(1):55-61. [PubMed 25037695]Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689. doi: 10.1016/j.ahj.2014.07.028. [PubMed 25440796]Schwartz GG, Steg PG, Szarek M, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. [PubMed 30403574]Topic 103073 Version 140.0

Lixisenatide: Drug information

CloseLixisenatide: Drug informationLixisenatide: Drug information(For additional information see "Lixisenatide: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAdlyxin;Adlyxin Starter PackBrand Names: CanadaAdlyxinePharmacologic CategoryAntidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor AgonistDosing: AdultNote: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (AACE/ACE [Garber 2020]).Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or those who cannot take metformin; use is not associated with improvements in cardiovascular outcomes (ADA 2020; Pfeffer 2015).SUBQ: Initial: 10 mcg once daily for 14 days; on day 15 increase to 20 mcg once daily. Maintenance dose: 20 mcg once daily.Missed dose: If dose is missed, administer within one hour of next meal.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdulteGFR ≥30 to 89 mL/minute/1.73 m2: No dosage adjustment necessary; monitor closely for increased adverse GI effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration and worsening of renal function.eGFR 15 to 29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (limited data); exposure is increased in these patients. Monitor closely for increased adverse GI effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration and worsening of renal function.eGFR <15 mL/minute/1.73 m2: Use is not recommended (has not been studied).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, dosage adjustment not likely as hepatic impairment is not expected to affect lixisenatide pharmaco*kinetics.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Pen-injector Kit, Subcutaneous: Adlyxin Starter Pack: 10 mcg/0.2 mL & 20 mcg/0.2 mL (6 mL) [contains metacresol]Solution Pen-injector, Subcutaneous: Adlyxin: 20 mcg/0.2 mL (3 mL) [contains metacresol]Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Adlyxine: 10 mcg/0.2 mL (3 mL); 20 mcg/0.2 mL (3 mL) [contains metacresol]Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208471s005lbl.pdf#page=24, must be dispensed with this medication.Administration: AdultSubcutaneous: Administer subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites for each dose; do not use the same site for each injection. Administer within one hour before the first meal of the day, preferably the same meal each day. Solution should appear clear and colorless; do not use if particulate matter or coloration is seen. For each new prefilled pen, activate the device before the first injection by attaching a pen needle, pulling the injection button out, and then injecting into the air or a container (continue to depress the button until it stops and for an additional 2 seconds); these activation steps should not be performed for subsequent injections. Use a new needle for each injection. Once injected, continue to depress the button until it stops and for an additional 2 seconds. Then, remove the needle. Refer to manufacturer’s instructions for further details.Use: Labeled IndicationsDiabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.>10%:Gastrointestinal: Gastrointestinal signs and symptoms (40%; abdominal distension [2%], constipation [3%], diarrhea [8%], dyspepsia [3%], nausea [25%], upper abdominal pain [2%], vomiting [10%])Immunologic: Antibody development (70%; attenuated glycemic response: 2%)1% to 10%:Local: Injection-site reaction (4%; including erythema at injection site, injection-site pruritus, pain at injection site)Nervous system: Dizziness (7%), headache (9%)<1%: Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reactionPostmarketing:Gastrointestinal: Cholecystitis, cholelithiasis (requiring cholecystectomy), pancreatitis (acute, chronic, and edematous) (Chis 2018)Renal: Acute kidney injury, exacerbation of renal failureContraindicationsHistory of severe hypersensitivity to lixisenatide or any component of the formulation.Warnings/PrecautionsConcerns related to adverse effects:• Anti-lixisenatide antibodies: Use may be associated with the development of anti-lixisenatide antibodies. In clinical trials, high titers were observed in 2.4% of patients and were associated with an attenuated glycemic response. Allergic reactions and injection site reactions were more frequent in antibody positive patients; consider alternative antidiabetic therapy in patients not achieving targeted glycemic control or with worsening glycemic control and/or significant allergic or injection site reactions.• Gallbladder disease: Use of glucagon-like peptide-1 (GLP-1) agonists may increase risk of gallbladder and bile duct disease, including cholelithiasis and cholecystitis (Faillie 2016; Monami 2017; Pfeffer 2015). Cholelithiasis and cholecystitis have been reported with lixisenatide use.• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported; discontinue use if hypersensitivity reactions occur and treat promptly as indicated. It is not known if patients with a history of hypersensitivity to other GLP-1 agonists are at increased risk for hypersensitivity reactions with lixisenatide; patients with prior serious reactions to similar agents should be monitored closely.• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain which may radiate to the back, and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis.Disease-related concerns:• Bariatric surgery: - Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013). - Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial GLP-1 concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.• Gastroparesis: Lixisenatide slows gastric emptying and is not recommended for use in patients with gastroparesis (has not been studied); do not initiate therapy in patients with severe gastroparesis.• Renal impairment: Use with caution in patients with mild renal impairment (eGFR ≥60 to 89 mL/minute/1.73 m2) or moderate renal impairment (≥30 to <60 mL/minute/1.73 m2); may be at increased risk of adverse effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration, acute kidney injury and worsening of chronic renal failure. There is limited experience with severe impairment (eGFR 15 to <30 mL/minute/1.73 m2); lixisenatide exposure may be increased in these patients. Monitor all patients with renal impairment closely for decreasing renal function. Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2) (has not been studied).Dosage form specific issues:• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: Not for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHormonal Contraceptives: May diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modificationHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyInsulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins.Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationLiraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMeglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides.Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapySalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySemaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationSincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas.Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyReproductive ConsiderationsGlucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)Pregnancy ConsiderationsPoorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).Agents other than lixisenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).Breastfeeding ConsiderationsIt is not known if lixisenatide is present in breast milk.According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.Dietary ConsiderationsIndividualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapyMonitoring ParametersPlasma glucose; renal function; signs/symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back and that may or may not be accompanied by vomiting); signs/symptoms of gallbladder disease; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).Reference RangeRecommendations for glycemic control in patients with diabetes:Nonpregnant adults (ADA 2021):HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Older adults (≥65 years of age) (ADA 2021):Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).Classification of hypoglycemia (ADA 2021):Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.Mechanism of ActionLixisenatide is a selective glucagon-like peptide-1 (GLP-1) receptor agonist. Acting on the same receptor as the endogenous hormone incretin, lixisenatide increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, and slows gastric emptying.Pharmaco*kineticsDistribution: Vz/F: ~100 LMetabolism: Presumed to undergo proteolytic degradationHalf-life elimination: ~3 hoursTime to peak: 1 to 3.5 hoursExcretion: UrinePharmaco*kinetics: Additional ConsiderationsAltered kidney function: Compared to healthy subjects (CrCl ≥90 mL/minute), lixisenatide Cmax and AUC were increased by 60% and 34% in mild renal impairment (CrCl 60 to 89 mL/minute), by 42% and 69% in moderate renal impairment (CrCl 30 to 59 mL/minute), and by 83% and 124% in severe renal impairment (CrCl 15 to 29 mL/minute) respectively.Pricing: USPen-injector Kit (Adlyxin Starter Pack Subcutaneous)10 & 20MCG/0.2ML (per mL): $135.71Solution Pen-injector (Adlyxin Subcutaneous)20MCG/0.2ML (per mL): $135.70Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalLyxumia (AE, AR, AT, AU, BE, BR, CR, CY, CZ, DK, DO, EE, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, IE, IL, IS, JP, KR, KW, LB, LT, LU, LV, MT, NI, NL, NO, PA, PH, PL, PT, RO, SI, SK, SV, TW)For country code abbreviations (show table)Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; June 2022.Alexopoulos AS, Blair R, Peters AL. Management of preexisting diabetes in pregnancy: a review. JAMA. 2019;321(18):1811-1819. doi:10.1001/jama.2019.4981 [PubMed 31087027]American College of Obstetricians and Gynecologists (ACOG) practice bulletin no. 201: pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960. [PubMed 30461693]American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care.diabetesjournals.org/content/44/Supplement_1. Accessed January 13, 2021.Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. doi: 10.1210/jc.2013-2465. [PubMed 24194617]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed September 20, 2016.Chis BA, Fodor D. Acute pancreatitis during GLP-1 receptor agonist treatment. A case report. Clujul Med. 2018;91(1):117-119. doi:10.15386/cjmed-804 [PubMed 29440961]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669‐2701. doi:10.2337/dci18-0033 [PubMed 30291106]Egan AM, Dow ML, Vella A. A review of the pathophysiology and management of diabetes in pregnancy. Mayo Clin Proc. 2020;95(12):2734-2746. doi:10.1016/j.mayocp.2020.02.019 [PubMed 32736942]Faillie JL, Yu OH, Yin H, Hillaire-Buys D, Barkun A, Azoulay L. Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus. JAMA Intern Med. 2016;176(10):1474‐1481. doi:10.1001/jamainternmed.2016.1531 [PubMed 27478902]Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. doi:10.4158/cs-2019-0472 [PubMed 32022600]Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115. doi: 0.1016/j.kint.2020.06.019 [PubMed 32998798]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi: 10.1038/ijo.2009.79. [PubMed 19417773]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104(5):1520‐1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis. 2013;9(2):159-191. doi: 10.1016/j.soard.2012.12.010. [PubMed 23537696]Monami M, Nreu B, Scatena A, et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials. Diabetes Obes Metab. 2017;19(9):1233‐1241. doi:10.1111/dom.12926 [PubMed 28244632]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi: 10.1007/s11695-012-0622-3. [PubMed 22354457]Pfeffer MA, Claggett B, Diaz R, et al; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247‐2257. doi:10.1056/NEJMoa1509225 [PubMed 26630143]Topic 109304 Version 96.0

Exenatide: Pediatric drug information

CloseExenatide: Pediatric drug informationExenatide: Pediatric drug information(For additional information see "Exenatide: Drug information" and see "Exenatide: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)ALERT: US Boxed WarningRisk of thyroid C-cell tumors (Bydureon):Exenatide extended release (ER) causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared with controls. It is unknown whether exenatide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of exenatide-ER-induced rodent thyroid C-cell tumors has not been determined. Exenatide ER is contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of exenatide ER and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with exenatide ER.Brand Names: USBydureon BCise;Bydureon [DSC];Byetta 10 MCG Pen;Byetta 5 MCG PenBrand Names: CanadaBydureon [DSC];Byetta 10 MCG Pen [DSC];Byetta 5 MCG Pen [DSC]Therapeutic CategoryAntidiabetic Agent, Incretin MimeticDosing: PediatricDiabetes mellitus, type 2; adjunct to diet and exerciseDiabetes mellitus, type 2; adjunct to diet and exercise: Children ≥10 years and Adolescents: Extended-release injection (Bydureon/Bydureon BCise): SUBQ: 2 mg once weekly without regard to meals.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricChildren ≥10 years and Adolescents: Extended-release injection:eGFR ≥45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; pharmaco*kinetic trials in adults report higher exposure; use caution; monitor for hypovolemia.eGFR <45 mL/minute/1.73 m2: Use is not recommended.End-stage renal disease: Use is not recommended.Dosing: Hepatic Impairment: PediatricChildren ≥10 years and Adolescents: Extended-release injection: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Adult(For additional information see "Exenatide: Drug information")Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or who cannot take metformin. May be preferred when weight loss is desired and/or in patients with an HbA1c relatively far from goal (eg, HbA1c 9% to 10%) and type 1 diabetes is not likely; use has not been associated with improved or worsened cardiovascular outcomes (ADA 2021; Holman 2017; Wexler 2020).Immediate release: SUBQ: Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the 2 main meals of the day, ≥6 hours apart); may increase to 10 mcg twice daily after 1 month if needed to achieve glycemic goals.Missed dose: Missed dose should be skipped; resume at the next scheduled dose.Extended release: SUBQ: 2 mg once weekly without regard to meals. If changing the day of administration is necessary, allow at least 3 days between 2 doses.Missed dose: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.Conversion from immediate release to extended release:Initiate weekly administration of exenatide extended release the day after discontinuing exenatide immediate release. Note: May experience increased blood glucose levels for ~2 to 4 weeks after conversion. Pretreatment with exenatide immediate release is not required when initiating exenatide extended release.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultImmediate release:CrCl ≥30 mL/minute: No dosage adjustment necessary; use caution with initiation of therapy or when increasing the dose in patients with CrCl 30 to 50 mL/minute; monitor for hypovolemia.CrCl <30 mL/minute: Use is not recommended.ESRD: Use is not recommended.Extended release:eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary; use caution, monitor for hypovolemia.eGFR 30 to <45 mL/minute/1.73 m2: Use is not recommended per manufacturer's labeling. However, some data have shown similar safety and efficacy in patients with an eGFR 30 to <60 mL/minute/1.73 m2 compared to those with an eGFR ≥60 mL/minute/1.73 m2; use with caution and monitor carefully (Bethel 2020; Guja 2020; Holman 2017).eGFR <30 mL/minute/1.73 m2: Use is not recommended.ESRD: Use is not recommended.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, the need for dosage adjustment is unlikely as hepatic dysfunction is not expected to affect exenatide pharmaco*kinetics.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productAuto-injector, Subcutaneous: Bydureon BCise: 2 mg/0.85 mL (0.85 mL)Pen-injector, Subcutaneous [preservative free]: Bydureon: 2 mg (1 ea [DSC])Solution Pen-injector, Subcutaneous: Byetta 10 MCG Pen: 10 mcg/0.04 mL (2.4 mL) [contains metacresol]Byetta 5 MCG Pen: 5 mcg/0.02 mL (1.2 mL) [contains metacresol]Suspension Reconstituted ER, Subcutaneous: Bydureon: 2 mg (1 ea [DSC])Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productPen-injector, Subcutaneous: Bydureon: 2 mg ([DSC])Solution Pen-injector, Subcutaneous: Byetta 10 MCG Pen: 10 mcg/0.04 mL ([DSC]) [contains metacresol]Byetta 5 MCG Pen: 5 mcg/0.02 mL ([DSC]) [contains metacresol]Dosage Forms ConsiderationsBydureon: Extended release formulationByetta: Immediate release formulationMedication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:Bydureon: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022200s033lbl.pdf#page=36Bydureon BCise: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209210s021lbl.pdf#page=33Byetta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021773s046s047lbl.pdf#page=33Administration: PediatricParenteral: SUBQ: Extended release: Bydureon, Bydureon BCise: Administer via SUBQ injection in the back of the upper arm, thigh, or abdomen; rotate injection sites; may inject in the same body region each week but administer in a different injection site. Do not inject IV or IM. If using concomitantly with insulin, administer as separate injections (do not mix in same syringe); may inject in the same body region as insulin but not adjacent to one another. May administer without regard to meals or time of day. May self-administer with proper training; caregivers should assist pediatric patients. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer's labeling).Bydureon single-dose tray: Administer immediately after reconstitution; the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.Bydureon Pen: Allow pen to come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix; rotate pen every 10 taps (may need to tap 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing; see product labeling for detailed injection instructions. To ensure full dose is delivered, after insertion of needle press, injection button until it clicks and hold for 10 seconds.Bydureon BCise autoinjector: Allow autoinjector to rest flat and come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for ≥15 seconds; suspension should appear opaque and white to off-white and evenly mixed and there should no longer be any white along the sides, bottom, or top; may take longer to mix if not stored flat. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.Changing day of administration: If changing the day of administration is necessary, allow ≥3 days between 2 doses.Missed dose: Extended-release injection: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.Administration: AdultSUBQ: Administer via SUBQ injection in the upper arm, thigh, or abdomen; rotate injection sites. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another. Do not inject IV or IM.Immediate release: Use only if clear, colorless, and free of particulate matter. Administer within 60 minutes prior to morning and evening meal (or prior to the 2 main meals of the day, approximately ≥6 hours apart). Set up each new pen before the first use by priming it. See pen user manual for further details. Dial the dose into the dose window before each administration.Extended release: May administer without regard to meals or time of day. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer’s labeling).Bydureon single-dose tray: Administer immediately after reconstitution in diluent, the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.Bydureon Pen: Allow pen to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix (may need to tap up to 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, after insertion of needle press injection button until it clicks and hold for 10 seconds.Bydureon BCise autoinjector: Allow autoinjector to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for at least 15 seconds; suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.Hazardous Drugs Handling ConsiderationsThis medication is not on the National Institute for Occupational Safety and Health (NIOSH) (2016) list; however, it may meet the criteria for a hazardous drug. Exenatide may cause carcinogenicity, teratogenicity, reproductive toxicity and has a structural or toxicity profile similar to existing hazardous agents.Note: Prepared/prefilled syringes may be excluded from some hazardous drug handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2018). Refer to institution-specific handling policies and procedures.Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends double gloving and a protective gown during subcutaneous administration from a prepared/prefilled syringe (NIOSH 2016).Storage/StabilityBydureon single-dose tray or pen: Store under refrigeration at 2°C to 8°C (36°F to 46°F); vials/pens may be stored at ≤25°C (≤77°F) for up to 4 weeks. Do not freeze (discard if freezing occurs). Protect from light.Bydureon BCise autoinjector: Store under refrigeration at 2°C to 8°C (36°F to 46°F); if necessary, may store at ≤30°C (≤86°F) for up to 4 weeks. Protect from light. Must be stored flat.Byetta: Prior to initial use, store under refrigeration at 2°C to 8°C (36°F to 46°F); after initial use, may store at ≤25°C (≤77°F). Do not freeze (discard if freezing occurs). Protect from light. Pen should be discarded 30 days after initial use.UseTreatment of type 2 diabetes mellitus (DM) as an adjunct to diet and exercise to improve glycemic control (Extended-release injection [Bydureon, Bydureon BCise]: FDA approved in ages ≥10 years and adults; Immediate-release injection: [Byetta]: FDA approved in adults).Note: Exenatide is not indicated for the treatment of type 1 DM. Extended-release exenatide injection is not recommended first line for patients inadequately controlled on diet and exercise.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence rates are reported for monotherapy use.>10%:Gastrointestinal: Diarrhea (extended release: 4% to 11%; immediate release: 1% to 2%), nausea (8% to 11%)Immunologic: Antibody development (antibody titers commonly decrease with continued use, though a small percentage of patients had increased titers; an attenuated glycemic response may be seen with antibody formation)Local: Injection-site nodule (extended release: autoinjector: 11%; pen: 77%), injection-site reaction (13% to 24%; reactions were more common with extended-release formulations in antibody-positive patients)1% to 10%:Endocrine & metabolic: Hypoglycemia (2% to 5%, including severe hypoglycemia)Gastrointestinal: Constipation (2% to 9%), decreased appetite (immediate release: 1% to 2%), dyspepsia (3% to 7%), gallbladder disease (≤2%; including cholecystitis or cholelithiasis), vomiting (3% to 4%)Local: Erythema at injection site (extended release: 2%), injection-site pruritus (extended release: 3%)Nervous system: Dizziness (1% to 3%), headache (4% to 8%)Postmarketing:Cardiovascular: Increased heart rate (Robinson 2013), prolongation P-R interval on ECG (Linnebjerg 2011)Dermatologic: Alopecia, macular eruption, papular rash, pruritus, urticariaGastrointestinal: Abdominal distention, abdominal pain, acute pancreatitis, dysgeusia, eructation, flatulence, hemorrhagic pancreatitis, necrotizing pancreatitisHematologic & oncologic: Immune thrombocytopeniaHypersensitivity: Anaphylaxis, angioedema, severe hypersensitivity reactionLocal: Abscess at injection site, cellulitis at injection site, tissue necrosis at injection siteNervous system: DrowsinessRenal: Acute kidney injury, exacerbation of renal failure, increased serum creatinine, kidney transplant dysfunction, renal insufficiencyContraindicationsPrior serious hypersensitivity to exenatide or any component of the formulation; history of or family history of medullary thyroid carcinoma (exenatide ER only); patients with multiple endocrine neoplasia syndrome type 2 (exenatide ER only); history of drug-induced immune-mediated thrombocytopenia.Canadian labeling: Additional contraindications (not in US labeling):Bydureon: End-stage renal disease (ESRD) or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.Byetta: Diabetic ketoacidosis, diabetic coma/precoma or type 1 diabetes mellitus; ESRD or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.Warnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported; discontinue therapy in the event of a hypersensitivity reaction. Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules have been reported with use. Isolated cases required surgical intervention.• Gallbladder disease: Cases of cholelithiasis and cholecystitis have been reported; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.• GI symptoms: Most common reactions are GI related; these symptoms may be dose-related and may decrease in frequency/severity with gradual titration and continued use.• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back, and that may or may not be accompanied by vomiting). Prior to initiating therapy, consider other factors associated with pancreatitis that may be present (eg, hypertriglyceridemia, ethanol abuse, cholelithiasis); it is unknown if exenatide increases the risk for pancreatitis in these patients. If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis.• Renal effects: Cases of acute renal failure and chronic renal failure exacerbation, including severe cases requiring hemodialysis or kidney transplantation, have been reported. May cause nausea/vomiting/diarrhea with transient hypovolemia that can worsen renal function. Renal dysfunction was usually reversible with appropriate corrective measures, including discontinuation of exenatide. Risk may be increased in patients receiving concomitant medications affecting renal function and/or hydration status.• Thrombocytopenia: Serious bleeding (may be fatal) from drug-induced immune-mediated thrombocytopenia has been reported. Discontinue use and do not reinitiate therapy if drug-induced thrombocytopenia is suspected; thrombocytopenia may persist for ~10 weeks after discontinuation of therapy.• Thyroid tumors: Bydureon: [US Boxed Warning] Thyroid C-cell tumors have developed in animal studies with exenatide ER; it is not known if exenatide ER causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Patients should be counseled on the potential risk of MTC with the use of exenatide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use of exenatide ER is contraindicated in patients with a personal or a family history of medullary thyroid cancer and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam; routine monitoring of serum calcitonin or using thyroid ultrasound for early detection of MTC is of unknown value. Cases of MTC in humans have been reported with the GLP-1 agonist, liraglutide.Disease-related concerns:• Bariatric surgery:- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.• GI disease: Not recommended to be used in patients with gastroparesis or severe GI disease due to frequent GI adverse effects associated with use.• Renal impairment: Use is not recommended in patients with a CrCl <30 mL/minute (exenatide) or <45 mL/minute (exenatide ER) or end-stage renal disease (ESRD). If used in renal transplant recipients, monitor for hypovolemia.Dosage form specific issues:• Injection-site reactions: Bydureon: Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules, have been reported.• Multiple dose injection pens: According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: Not for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis.• Duplicate therapy: Avoid concurrent use of extended-release (weekly) and immediate-release (daily) exenatide formulations.• Pediatric: Unlike the extended-release formulations (Bydureon, Bydureon BCise), the immediate-release formulation (Byetta) did not show efficacy in the treatment of type 2 diabetes mellitus in pediatric patients 10 to 17 years of age in clinical trials.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAlpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHormonal Contraceptives: May diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modificationHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyInsulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins.Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationLiraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMeglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides.Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapySalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySemaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationSincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas.Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyWarfarin: Exenatide may enhance the anticoagulant effect of Warfarin.Risk C: Monitor therapyReproductive ConsiderationsGlucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)Pregnancy ConsiderationsBased on in vitro data, exenatide has a low potential to cross the placenta (Hiles 2003).Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).Agents other than exenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).Monitoring ParametersPlasma glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors), HbA1c (monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change) (ADA 2021); renal function (SCr, BUN); volume/hydration status; signs/symptoms of pancreatitis (amylase, lipase, persistent abdominal pain); triglycerides; signs/symptoms of gallbladder disease; GI symptoms (nausea, vomiting, diarrhea).Reference RangePlasma Blood Glucose and HbA1c Goals for Diabetes Patients: Note: Postprandial blood glucose should be measured when there is a discrepancy between preprandial blood glucose concentrations and HbA1c values and to help assess glycemia for patients who receive basal/bolus or pump regimens. It is usually drawn 1 to 2 hours after starting a meal and is considered to be the "peak."Children ≥10 years and Adolescents:Preprandial glucose: 70 to 130 mg/dL (ISPAD [DiMeglio 2018]).Postprandial glucose: 90 to 180 mg/dL (ISPAD [DiMeglio 2018]).Bedtime glucose: 80 to 140 mg/dL (ISPAD [DiMeglio 2018]).HbA1c: <7%; Target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, or have extensive comorbid conditions (ADA 2020; ISPAD [DiMeglio 2018]).Adults, nonpregnant (ADA 2021):Preprandial glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Postprandial glucose: <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is similar to a goal HbA1c <7%.Mechanism of ActionExenatide is an analog of the hormone incretin (glucagon-like peptide 1 or GLP-1) which increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth/replication, slows gastric emptying, and decreases food intake. Exenatide administration results in decreases in hemoglobin A1c by approximately 0.5% to 1% (immediate release) or 1.5% to 1.9% (extended release).Pharmaco*kinetics (Adult data unless noted)Note: In pediatric patients ≥11 years of age, pharmaco*kinetic parameters of the extended-release formulation were reported to be similar to adults.Distribution: Vd: 28.3 LMetabolism: Minimal systemic metabolism; proteolytic degradation may occur following glomerular filtrationHalf-life elimination:Immediate release (daily) formulation: 2.4 hoursExtended release (weekly) formulation: ~2 weeksTime to peak, plasma: SubQ:Immediate release (daily) formulation: 2.1 hoursExtended release (weekly) formulation: Single dose: Initial period of release of surface-bound exenatide is followed by a gradual release from microspheres with peaks at week 2 and week 6 to 7 respectively; with once-weekly dosing steady state is achieved at 6 to 7 weeks (Bydureon) and 10 weeks (Bydureon BCise).Excretion: Urine (majority of dose)Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: In patients with mild to moderate renal impairment, exposure to exenatide was increased compared with patients with normal renal function.Pricing: USAuto-injector (Bydureon BCise Subcutaneous)2MG/0.85ML (per 0.85 mL): $233.98Solution Pen-injector (Byetta 10 MCG Pen Subcutaneous)10 mcg/0.04 mL (per mL): $400.58Solution Pen-injector (Byetta 5 MCG Pen Subcutaneous)5 mcg/0.02 mL (per mL): $801.16Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalBaietta (CR, DO, GT, HN, MX, NI, PA, SV);Bydureon (AE, AT, AU, BE, BH, CH, CR, CZ, DE, DK, DO, EG, ES, GB, GT, HN, IE, IL, JP, KR, LB, LT, LU, LV, MT, MX, NI, NL, NO, NZ, PA, PL, SE, SG, SI, SK, SV);Bydureon BCise (AU);Byetta (AE, AT, AU, BB, BE, BG, BH, CH, CL, CN, CO, CY, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IS, IT, JO, JP, KR, KW, LT, LU, LV, MT, MY, NL, NO, NZ, PH, PK, PL, PT, QA, RO, RU, SA, SE, SI, SK, TH, TR, TW, ZA)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2018:84-103.Alexopoulos AS, Blair R, Peters AL. Management of preexisting diabetes in pregnancy: a review. JAMA. 2019;321(18):1811-1819. doi:10.1001/jama.2019.4981 [PubMed 31087027]American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi:10.1097/AOG.0000000000002960 [PubMed 30461693]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care.diabetesjournals.org/content/44/Supplement_1. Accessed January 13, 2021.Bethel MA, Mentz RJ, Merrill P, et al. Microvascular and cardiovascular outcomes according to renal function in patients treated with once-weekly exenatide: insights from the EXSCEL trial. Diabetes Care. 2020;43(2):446-452. doi:10.2337/dc19-1065 [PubMed 31757838]Blevins T, Pullman J, Malloy J, et al. DURATION-5: Exenatide Once Weekly Resulted in Greater Improvements in Glycemic Control Compared With Exenatide Twice Daily in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310. [PubMed21307137]Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617]Bydureon (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; January 2020.Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2022.Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2021.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2020.Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2021.Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Byetta (exenatide) injection [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; November 2021.Byetta (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; December 2019.Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]DiMeglio LA, Acerini CL, Codner E, et al. ISPAD clinical practice consensus guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes. 2018;19(suppl 27):105-114. doi:10.1111/pedi.12737 [PubMed 30058221]Egan AM, Dow ML, Vella A. A review of the pathophysiology and management of diabetes in pregnancy. Mayo Clin Proc. 2020;95(12):2734-2746. doi:10.1016/j.mayocp.2020.02.019 [PubMed 32736942]Guja C, Frías JP, Suchower L, et al. Safety and efficacy of exenatide once weekly in participants with type 2 diabetes and stage 2/3 chronic kidney disease. Diabetes Ther. 2020;11(7):1467-1480. doi:10.1007/s13300-020-00815-z [PubMed 32306296]Hiles RA, Bawdon RE, Petrella EM. Ex vivo Human Placental Transfer of the Peptides Pramlintide and Exenatide (Synthetic Exendin-4). Hum Exp Toxicol. 2003;22(12):623-628. [PubMed 14992323]Holman RR, Bethel MA, Mentz RJ, et al; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228-1239. doi:10.1056/NEJMoa1612917 [PubMed 28910237]Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(supp 4):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]Kirkman M, Briscoe VJ, Clark N, et al. Diabetes in Older Adults: A Consensus Report. J Am Geriatr Soc. 2012. doi:10.1111/jgs.12035 [PubMed 23106132]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]Linnebjerg H, Seger M, Kothare PA, et al. A thorough QT study to evaluate the effects of single-dose exenatide 10 µg on cardiac repolarization in healthy subjects. Int J Clin Pharmacol Ther. 2011;49(10):594-604. [PubMed 21961484]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures -2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3(1):e001986. doi:10.1136/bmjopen-2012-001986 [PubMed 23355666]Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes. Diabetes Ther. 2019;10(1):5-19. doi:10.1007/s13300-018-0535-9 [PubMed 30506340]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed October 30, 2019.Wexler DJ. Initial management of blood glucose in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 14, 2020.Topic 132373 Version 33.0

Follitropin alfa (recombinant human follicle stimulating hormone): Drug information

CloseFollitropin alfa (recombinant human follicle stimulating hormone): Drug informationFollitropin alfa (recombinant human follicle stimulating hormone): Drug information(For additional information see "Follitropin alfa (recombinant human follicle stimulating hormone): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USGonal-f;Gonal-f RFF;Gonal-f RFF RedijectBrand Names: CanadaGonal-f;Gonal-f PenPharmacologic CategoryGonadotropin;Ovulation StimulatorDosing: AdultNote: Dose should be individualized. Use the lowest dose consistent with the expectation of good results. Over the course of treatment, doses may vary depending on individual patient response.Ovulation inductionOvulation induction: SubQ: Initial: 75 units daily for 14 days in the first cycle; incremental dose adjustments of up to 37.5 units may be considered after 14 days based on ovarian response; further dose increases of the same magnitude can be made, if necessary, every 7 days (maximum dose: 300 units daily). Treatment should be continued until follicular growth and/or serum estradiol levels indicate an adequate ovarian response. If response to follitropin is appropriate, human chorionic gonadotropin (hCG) is given 1 day following the last dose to induce final oocyte maturation and ovulation. Follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome. In general, therapy should not exceed 35 days.Multifollicular development during assisted reproductive technologyMultifollicular development during assisted reproductive technology: SubQ: Initiate therapy with follitropin alfa in the early follicular phase (cycle day 2 or day 3) at a dose of 150 units daily, until sufficient follicular development is attained. In most cases, therapy should not exceed 10 days. In patients whose endogenous gonadotropin levels are suppressed, initiate follitropin alfa at a dose of 225 units daily. Continue treatment until adequate follicular development is indicated as determined by ultrasound in combination with measurement of serum estradiol levels. Consider adjustments to dose after 5 days based on the patient's response; adjust subsequent dosage every 3 to 5 days by ≤75 to 150 units additionally at each adjustment. Doses >450 units daily are not recommended. Once adequate follicular development is evident, administer hCG to induce final follicular maturation in preparation for oocyte retrieval. Withhold hCG if the ovaries are abnormally enlarged.Spermatogenesis inductionSpermatogenesis induction: Gonal-f: SubQ: Therapy should begin with hCG pretreatment until serum testosterone is in normal range, then initiate follitropin alfa at 150 units 3 times weekly with hCG 3 times weekly; continue with lowest dose needed to induce spermatogenesis (maximum dose: 300 units 3 times weekly); may be given for up to 18 months.Dosing: Kidney Impairment: AdultThere are no dosage adjustment provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: AdultThere are no dosage adjustment provided in the manufacturer's labeling (has not been studied).Dosing: Older AdultRefer to adult dosing. Clinical studies did not include patients >65 years. Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Gonal-f RFF Rediject: 300 units/0.5 mL (0.5 mL); 450 units/0.75 mL (0.75 mL); 900 units/1.5 mL (1.5 mL) [contains metacresol]Solution Reconstituted, Injection: Gonal-f: 450 units (1 ea); 1050 units (1 ea) [contains benzyl alcohol]Solution Reconstituted, Subcutaneous: Gonal-f RFF: 75 units (1 ea)Generic Equivalent Available: USNoDosage Forms ConsiderationsGonal-f 450 unit and 1050 unit multi-dose vials are packaged with a diluent (bacteriostatic water for injection in a prefilled syringe) that contains benzyl alcohol.Dosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productSolution Pen-injector, Subcutaneous: Gonal-f Pen: 300 units/0.5 mL (0.5 mL); 450 units/0.75 mL (0.75 mL); 900 units/1.5 mL (1.5 mL) [contains metacresol]Solution Reconstituted, Injection: Gonal-f: 450 units ([DSC]); 1050 units ([DSC])Solution Reconstituted, Subcutaneous: Gonal-f: 37.5 units (1 ea); 75 units (1 ea); 150 units (1 ea)Administration: AdultSubQ: Administer SubQ in the abdomen, upper arm, or upper leg. Contents of multidose vials (Gonal-f or Gonal-f RFF) should be administered using the calibrated syringes provided by the manufacturer. Do not shake solution; allow any bubbles to settle prior to administration. Allow Gonal-f RFF Rediject to warm to room temperature for at least 30 minutes prior to administration to avoid discomfort from cold injection. Do not mix other medications inside of the Gonal-f RFF Rediject device.Use: Labeled IndicationsMultifollicular development during assisted reproductive technology: To stimulate the development of multiple follicles with assisted reproductive technology.Ovulation induction: Induction of ovulation and pregnancy in oligo-anovulatory infertile patients in whom the cause of infertility is functional and not caused by primary ovarian failure.Spermatogenesis induction (Gonal-f only): Induction of spermatogenesis in men with azoospermia and primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentage may vary by indication, product formulation. As reported with females, unless otherwise noted.>10%:Dermatologic: Acne vulgaris (males: 27%)Endocrine & metabolic: Ovarian cyst (4% to 15%)Gastrointestinal: Abdominal pain (5% to 23%), enlargement of abdomen (14%)Local: Pain at injection site (males: 11%; females: 5% to 6%)Nervous system: Headache (10% to 27%)1% to 10%:Dermatologic: Seborrhea (males: 5%)Endocrine & metabolic: Decreased libido (males: 3%), gynecomastia (males: 6%), intermenstrual bleeding (5%), ovarian hyperstimulation syndrome (5% to 7%)Gastrointestinal: Diarrhea (4%), flatulence (4% to 6%), nausea (4% to 8%)Genitourinary: Pelvic pain (7%)Local: Bruising at injection site (10%), inflammation at injection site (2% to 4%), injection site reaction (4%), swelling at injection site (3%)Nervous system: Fatigue (males: 10%), pain (5%)Postmarketing:Cardiovascular: ThromboembolismEndocrine & metabolic: Ovary enlargementHematologic & oncologic: Ovarian neoplasmHypersensitivity: Anaphylaxis, hypersensitivity reaction (including severe hypersensitivity reaction), nonimmune anaphylaxisRespiratory: Asthma, pulmonary complications (including atelectasis, acute respiratory distress syndrome, exacerbation of asthma)Miscellaneous: Ovarian torsionContraindicationsHypersensitivity to recombinant human follicle-stimulating hormone (FSH) products or any component of the formulation; high levels of FSH indicating primary gonadal failure; sex hormone dependent tumors of the reproductive tract and accessory organs; pituitary or hypothalamus tumors; uncontrolled thyroid, pituitary, or adrenal dysfunction; abnormal uterine bleeding of undetermined origin; ovarian cysts or enlargement of undetermined origin.Canadian labeling: Additional contraindications (not in US labeling): Presence of any cause for infertility other than anovulation (unless candidate for assisted reproductive technology); lactation.Warnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis have been reported; discontinue use for serious reactions and treat appropriately.• Ovarian enlargement: The lowest effective dose should be used to decrease the risk of abnormal ovarian enlargement. If ovaries are abnormally enlarged on the last day of follitropin alfa treatment, follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS).• Ovarian hyperstimulation syndrome: OHSS is a rare, exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of human chorionic gonadotropin treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. Decreased CrCl, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; Shmorgun 2017).• Ovarian torsion: Has been reported following gonadotropin treatment; may be related to OHSS, prior ovarian torsion, prior or current ovarian cyst, polycystic ovaries, pregnancy, or prior abdominal surgery. Early diagnosis and prompt detorsion may limit the extent of ovarian damage.• Pulmonary effects: Serious pulmonary conditions (atelectasis, acute respiratory distress syndrome, and exacerbation of asthma) have been reported.• Thromboembolic events: In association with and separate from OHSS, thromboembolic events have been reported. Risk may be increased in patients with severe obesity, thrombophilia, or a personal or family history of risk factors for thrombosis.Dosage form specific issues:• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: To minimize risks, use only at the lowest effective dose. Monitor ovarian response with transvagin*l ultrasound; concurrent measurement of estradiol levels may also be useful.• Experienced physician: These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management.• Multiple births: May result from the use of these medications; advise patient of the potential risk of multiple births before starting the treatment.Metabolism/Transport EffectsNone known.Drug InteractionsThere are no known significant interactions.Reproductive ConsiderationsFollitropin alfa is used for the induction of ovulation in oligo-anovulatory infertile patients and to stimulate the development of multiple follicles during assisted reproductive technology in patients who wish to become pregnant. Evaluate current pregnancy status as well as the fertility of the male partner prior to treatment.When used for the induction of spermatogenesis, exclude primary testicular failure and normalize testosterone levels prior to treatment. Evaluate fertility status of the female partner prior to induction of spermatogenesis when treating males with hypogonadotropic hypogonadism (AACE [Petak 2002]).Pregnancy ConsiderationsFollitropin alfa is used in the management of patients who wish to become pregnant; use is not indicated for patients who are already pregnant.Ectopic pregnancy, congenital abnormalities, spontaneous abortion, and multiple births have been reported. The incidence of congenital abnormality may be slightly higher after in vitro fertilization or intracytoplasmic sperm injection than with spontaneous conception. The higher incidence of congenital abnormalities and spontaneous abortion may be related to parenteral characteristics (maternal age, sperm characteristics) and not specifically associated with gonadotropin use.Breastfeeding ConsiderationsIt is not known if follitropin alfa is present in breast milk.Prolactin secretion during lactation may lead to inadequate ovarian stimulation; therefore, breastfeeding is not recommended by the manufacturer.Monitoring ParametersMonitor follicular growth by transvagin*l ultrasound to determine adequate ovarian response and timing of human chorionic gonadotropin (hCG) administration. Concurrent measurement of estradiol levels may also be useful.Monitor for signs and symptoms of ovarian hyperstimulation syndrome (OHSS) for at least 2 weeks following hCG administration. Initial symptoms of moderate to severe OHSS may include a sensation of bloating, abdominal pain, rapid weight gain, and decreased urine output (Shmorgun 2017).OHSS: Monitoring of hospitalized patients should include albumin, degree of ascites, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, hydration, serum creatinine, urine output, urine-specific gravity, signs of thromboembolism, vital signs, weight (daily or as necessary), and liver enzymes (weekly) (Shmorgun 2017).Spermatogenesis: Monitor serum testosterone levels, sperm count.Mechanism of ActionFollitropin alfa is a human FSH preparation of recombinant DNA origin. Follitropins stimulate ovarian follicular growth in women who do not have primary ovarian failure, and stimulate spermatogenesis in men with hypogonadotrophic hypogonadism. FSH is required for normal follicular growth, maturation, gonadal steroid production, and spermatogenesis. Pharmaco*kineticsOnset of action: Peak effect:Spermatogenesis, median: 6.8-12.4 months (range 2.7-18.1 months) Follicle development: Within cycleAbsorption: SubQ: Absorption rate is slower than the elimination rateDistribution: Mean Vd: 0.7 L with in vitro fertilization/embryo transfer patientsBioavailability: ~66% to 76% in healthy female volunteers; 10% in in vitro fertilization/embryo transfer patientsHalf-life elimination:SubQ: 24-53 hours in healthy female volunteers; 32-41 hours in healthy male volunteersTime to peak: In healthy volunteers: Females: SubQ: 8-16 hoursMales: SubQ: 11-20 hoursExcretion: Clearance: IV: 0.6 L/hour in healthy female volunteersPricing: USSolution (reconstituted) (Gonal-f Injection)450 unit (per each): $1,621.321050 unit (per each): $3,783.08Solution (reconstituted) (Gonal-f RFF Subcutaneous)75 unit (per each): $270.22Solution Pen-injector (Gonal-f RFF Rediject Subcutaneous)300 units/0.5 mL (per 0.5 mL): $1,080.88450 unit/0.75 mL (per 0.75 mL): $1,621.32900 unit/1.5 mL (per mL): $2,161.76Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalBemfola (BE, CZ, DE, DK, EE, ES, FI, FR, GB, HR, HU, IE, IL, IS, LT, LU, LV, MT, NO, PL, PT, RO, SE, SI, SK);Forielle (CH);Gonal-F (AE, AR, AT, AU, BE, BG, BH, BR, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JO, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PH, PK, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, VN, ZA);Gonalef (JP, VE);Ovaleap (CZ, DE, DK, ES, FR, GB, HR, HU, IE, IL, LT, LU, LV, MT, PL, PT, RO, SK)For country code abbreviations (show table)Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Corbett S, Shmorgun D, Claman P, et al; Reproductive Endocrinology Infertility Committee. The prevention of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2014;36(11):1024-1033. doi: 10.1016/S1701-2163(15)30417-5. [PubMed 25574681]Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment. Reprod Biol Endocrinol. 2012;10:32. doi: 10.1186/1477-7827-10-32. [PubMed 22531097]Goa KL and Wagstaff AJ, “Follitropin Alpha in Infertility,” BioDrugs, 1998, 9(3):235-60. [PubMed 18020563]Gonal-f for injection (follitropin alfa) [prescribing information]. Rockland, MA: EMD Serono, Inc; May 2018.Gonal-f for injection (follitropin alfa) [prescribing information]. Rockland, MA: EMD Serono, Inc; February 2020.Gonal-f for injection (follitropin alfa) [product monograph]. Mississauga, Ontario, Canada: EMD Serono; October 2020.Gonal-f for subcutaneous injection (follitropin alfa) [prescribing information]. Rockland, MA: EMD Serono Inc; December 2020.Gonal-f pen (follitropin alfa) [product monograph]. Mississauga, Ontario, Canada: EMD Serono; May 2019.Gonal-f RFF Redi-ject for subcutaneous injection (follitropin alfa) [prescribing information]. Rockland, MA: EMD Serono Inc; December 2020.Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update. Endocr Pract. 2002;8(6):440-456. [PubMed 15260010]Practice Committee of the American Society for Reproductive Medicine (ASRM). Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634-1647. doi: 10.1016/j.fertnstert.2016.08.048. [PubMed 27678032]Shmorgun D, Claman P. No-268-The diagnosis and management of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2017;39(11):e479-e486. doi:10.1016/j.jogc.2017.09.003 [PubMed 29080733]Topic 8923 Version 160.0

Exenatide: Drug information

CloseExenatide: Drug informationExenatide: Drug information(For additional information see "Exenatide: Patient drug information" and see "Exenatide: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)ALERT: US Boxed WarningRisk of thyroid C-cell tumors (Bydureon):Exenatide extended release (ER) causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared with controls. It is unknown whether exenatide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of exenatide-ER-induced rodent thyroid C-cell tumors has not been determined. Exenatide ER is contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of exenatide ER and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with exenatide ER.Brand Names: USBydureon BCise;Bydureon [DSC];Byetta 10 MCG Pen;Byetta 5 MCG PenBrand Names: CanadaBydureon [DSC];Byetta 10 MCG Pen [DSC];Byetta 5 MCG Pen [DSC]Pharmacologic CategoryAntidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor AgonistDosing: AdultNote: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or who cannot take metformin. May be preferred when weight loss is desired and/or in patients with an HbA1c relatively far from goal (eg, HbA1c 9% to 10%) and type 1 diabetes is not likely; use has not been associated with improved or worsened cardiovascular outcomes (ADA 2021; Holman 2017; Wexler 2020).Immediate release: SUBQ: Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the 2 main meals of the day, ≥6 hours apart); may increase to 10 mcg twice daily after 1 month if needed to achieve glycemic goals.Missed dose: Missed dose should be skipped; resume at the next scheduled dose.Extended release: SUBQ: 2 mg once weekly without regard to meals. If changing the day of administration is necessary, allow at least 3 days between 2 doses.Missed dose: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.Conversion from immediate release to extended release:Initiate weekly administration of exenatide extended release the day after discontinuing exenatide immediate release. Note: May experience increased blood glucose levels for ~2 to 4 weeks after conversion. Pretreatment with exenatide immediate release is not required when initiating exenatide extended release.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultImmediate release:CrCl ≥30 mL/minute: No dosage adjustment necessary; use caution with initiation of therapy or when increasing the dose in patients with CrCl 30 to 50 mL/minute; monitor for hypovolemia.CrCl <30 mL/minute: Use is not recommended.ESRD: Use is not recommended.Extended release:eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary; use caution, monitor for hypovolemia.eGFR 30 to <45 mL/minute/1.73 m2: Use is not recommended per manufacturer's labeling. However, some data have shown similar safety and efficacy in patients with an eGFR 30 to <60 mL/minute/1.73 m2 compared to those with an eGFR ≥60 mL/minute/1.73 m2; use with caution and monitor carefully (Bethel 2020; Guja 2020; Holman 2017).eGFR <30 mL/minute/1.73 m2: Use is not recommended.ESRD: Use is not recommended.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, the need for dosage adjustment is unlikely as hepatic dysfunction is not expected to affect exenatide pharmaco*kinetics.Dosing: Pediatric(For additional information see "Exenatide: Pediatric drug information")Diabetes mellitus, type 2; adjunct to diet and exerciseDiabetes mellitus, type 2; adjunct to diet and exercise: Children ≥10 years and Adolescents: Extended-release injection (Bydureon/Bydureon BCise): SUBQ: 2 mg once weekly without regard to meals.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricChildren ≥10 years and Adolescents: Extended-release injection:eGFR ≥45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; pharmaco*kinetic trials in adults report higher exposure; use caution; monitor for hypovolemia.eGFR <45 mL/minute/1.73 m2: Use is not recommended.End-stage renal disease: Use is not recommended.Dosing: Hepatic Impairment: PediatricChildren ≥10 years and Adolescents: Extended-release injection: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productAuto-injector, Subcutaneous: Bydureon BCise: 2 mg/0.85 mL (0.85 mL)Pen-injector, Subcutaneous [preservative free]: Bydureon: 2 mg (1 ea [DSC])Solution Pen-injector, Subcutaneous: Byetta 10 MCG Pen: 10 mcg/0.04 mL (2.4 mL) [contains metacresol]Byetta 5 MCG Pen: 5 mcg/0.02 mL (1.2 mL) [contains metacresol]Suspension Reconstituted ER, Subcutaneous: Bydureon: 2 mg (1 ea [DSC])Generic Equivalent Available: USNoDosage Forms ConsiderationsBydureon: Extended release formulationByetta: Immediate release formulationDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productPen-injector, Subcutaneous: Bydureon: 2 mg ([DSC])Solution Pen-injector, Subcutaneous: Byetta 10 MCG Pen: 10 mcg/0.04 mL ([DSC]) [contains metacresol]Byetta 5 MCG Pen: 5 mcg/0.02 mL ([DSC]) [contains metacresol]Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:Bydureon: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022200s033lbl.pdf#page=36Bydureon BCise: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209210s021lbl.pdf#page=33Byetta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021773s046s047lbl.pdf#page=33Administration: AdultSUBQ: Administer via SUBQ injection in the upper arm, thigh, or abdomen; rotate injection sites. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another. Do not inject IV or IM.Immediate release: Use only if clear, colorless, and free of particulate matter. Administer within 60 minutes prior to morning and evening meal (or prior to the 2 main meals of the day, approximately ≥6 hours apart). Set up each new pen before the first use by priming it. See pen user manual for further details. Dial the dose into the dose window before each administration.Extended release: May administer without regard to meals or time of day. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer’s labeling).Bydureon single-dose tray: Administer immediately after reconstitution in diluent, the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.Bydureon Pen: Allow pen to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix (may need to tap up to 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, after insertion of needle press injection button until it clicks and hold for 10 seconds.Bydureon BCise autoinjector: Allow autoinjector to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for at least 15 seconds; suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.Administration: PediatricParenteral: SUBQ: Extended release: Bydureon, Bydureon BCise: Administer via SUBQ injection in the back of the upper arm, thigh, or abdomen; rotate injection sites; may inject in the same body region each week but administer in a different injection site. Do not inject IV or IM. If using concomitantly with insulin, administer as separate injections (do not mix in same syringe); may inject in the same body region as insulin but not adjacent to one another. May administer without regard to meals or time of day. May self-administer with proper training; caregivers should assist pediatric patients. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer's labeling).Bydureon single-dose tray: Administer immediately after reconstitution; the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.Bydureon Pen: Allow pen to come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix; rotate pen every 10 taps (may need to tap 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing; see product labeling for detailed injection instructions. To ensure full dose is delivered, after insertion of needle press, injection button until it clicks and hold for 10 seconds.Bydureon BCise autoinjector: Allow autoinjector to rest flat and come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for ≥15 seconds; suspension should appear opaque and white to off-white and evenly mixed and there should no longer be any white along the sides, bottom, or top; may take longer to mix if not stored flat. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.Changing day of administration: If changing the day of administration is necessary, allow ≥3 days between 2 doses.Missed dose: Extended-release injection: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.Hazardous Drugs Handling ConsiderationsThis medication is not on the National Institute for Occupational Safety and Health (NIOSH) (2016) list; however, it may meet the criteria for a hazardous drug. Exenatide may cause carcinogenicity, teratogenicity, reproductive toxicity and has a structural or toxicity profile similar to existing hazardous agents.Note: Prepared/prefilled syringes may be excluded from some hazardous drug handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2018). Refer to institution-specific handling policies and procedures.Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends double gloving and a protective gown during subcutaneous administration from a prepared/prefilled syringe (NIOSH 2016).Use: Labeled IndicationsDiabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults (immediate release and extended release) and pediatric patients ≥10 years of age (extended release only) with type 2 diabetes mellitus.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence rates are reported for monotherapy use.>10%:Gastrointestinal: Diarrhea (extended release: 4% to 11%; immediate release: 1% to 2%), nausea (8% to 11%)Immunologic: Antibody development (antibody titers commonly decrease with continued use, though a small percentage of patients had increased titers; an attenuated glycemic response may be seen with antibody formation)Local: Injection-site nodule (extended release: autoinjector: 11%; pen: 77%), injection-site reaction (13% to 24%; reactions were more common with extended-release formulations in antibody-positive patients)1% to 10%:Endocrine & metabolic: Hypoglycemia (2% to 5%, including severe hypoglycemia)Gastrointestinal: Constipation (2% to 9%), decreased appetite (immediate release: 1% to 2%), dyspepsia (3% to 7%), gallbladder disease (≤2%; including cholecystitis or cholelithiasis), vomiting (3% to 4%)Local: Erythema at injection site (extended release: 2%), injection-site pruritus (extended release: 3%)Nervous system: Dizziness (1% to 3%), headache (4% to 8%)Postmarketing:Cardiovascular: Increased heart rate (Robinson 2013), prolongation P-R interval on ECG (Linnebjerg 2011)Dermatologic: Alopecia, macular eruption, papular rash, pruritus, urticariaGastrointestinal: Abdominal distention, abdominal pain, acute pancreatitis, dysgeusia, eructation, flatulence, hemorrhagic pancreatitis, necrotizing pancreatitisHematologic & oncologic: Immune thrombocytopeniaHypersensitivity: Anaphylaxis, angioedema, severe hypersensitivity reactionLocal: Abscess at injection site, cellulitis at injection site, tissue necrosis at injection siteNervous system: DrowsinessRenal: Acute kidney injury, exacerbation of renal failure, increased serum creatinine, kidney transplant dysfunction, renal insufficiencyContraindicationsPrior serious hypersensitivity to exenatide or any component of the formulation; history of or family history of medullary thyroid carcinoma (exenatide ER only); patients with multiple endocrine neoplasia syndrome type 2 (exenatide ER only); history of drug-induced immune-mediated thrombocytopenia.Canadian labeling: Additional contraindications (not in US labeling):Bydureon: End-stage renal disease (ESRD) or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.Byetta: Diabetic ketoacidosis, diabetic coma/precoma or type 1 diabetes mellitus; ESRD or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.Warnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported; discontinue therapy in the event of a hypersensitivity reaction. Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules have been reported with use. Isolated cases required surgical intervention.• Gallbladder disease: Cases of cholelithiasis and cholecystitis have been reported; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.• GI symptoms: Most common reactions are GI related; these symptoms may be dose-related and may decrease in frequency/severity with gradual titration and continued use.• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back, and that may or may not be accompanied by vomiting). Prior to initiating therapy, consider other factors associated with pancreatitis that may be present (eg, hypertriglyceridemia, ethanol abuse, cholelithiasis); it is unknown if exenatide increases the risk for pancreatitis in these patients. If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis.• Renal effects: Cases of acute renal failure and chronic renal failure exacerbation, including severe cases requiring hemodialysis or kidney transplantation, have been reported. May cause nausea/vomiting/diarrhea with transient hypovolemia that can worsen renal function. Renal dysfunction was usually reversible with appropriate corrective measures, including discontinuation of exenatide. Risk may be increased in patients receiving concomitant medications affecting renal function and/or hydration status.• Thrombocytopenia: Serious bleeding (may be fatal) from drug-induced immune-mediated thrombocytopenia has been reported. Discontinue use and do not reinitiate therapy if drug-induced thrombocytopenia is suspected; thrombocytopenia may persist for ~10 weeks after discontinuation of therapy.• Thyroid tumors: Bydureon: [US Boxed Warning] Thyroid C-cell tumors have developed in animal studies with exenatide ER; it is not known if exenatide ER causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Patients should be counseled on the potential risk of MTC with the use of exenatide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use of exenatide ER is contraindicated in patients with a personal or a family history of medullary thyroid cancer and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam; routine monitoring of serum calcitonin or using thyroid ultrasound for early detection of MTC is of unknown value. Cases of MTC in humans have been reported with the GLP-1 agonist, liraglutide.Disease-related concerns:• Bariatric surgery:- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.• GI disease: Not recommended to be used in patients with gastroparesis or severe GI disease due to frequent GI adverse effects associated with use.• Renal impairment: Use is not recommended in patients with a CrCl <30 mL/minute (exenatide) or <45 mL/minute (exenatide ER) or end-stage renal disease (ESRD). If used in renal transplant recipients, monitor for hypovolemia.Dosage form specific issues:• Injection-site reactions: Bydureon: Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules, have been reported.• Multiple dose injection pens: According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: Not for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis.• Duplicate therapy: Avoid concurrent use of extended-release (weekly) and immediate-release (daily) exenatide formulations.• Pediatric: Unlike the extended-release formulations (Bydureon, Bydureon BCise), the immediate-release formulation (Byetta) did not show efficacy in the treatment of type 2 diabetes mellitus in pediatric patients 10 to 17 years of age in clinical trials.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHormonal Contraceptives: May diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modificationHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyInsulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins.Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationLiraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMeglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides.Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapySalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySemaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationSincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas.Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyWarfarin: Exenatide may enhance the anticoagulant effect of Warfarin.Risk C: Monitor therapyReproductive ConsiderationsGlucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)Pregnancy ConsiderationsBased on in vitro data, exenatide has a low potential to cross the placenta (Hiles 2003).Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).Agents other than exenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).Breastfeeding ConsiderationsIt is not known if exenatide is present in breast milk.According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.Monitoring ParametersSerum glucose; renal function; volume status; weight; triglycerides; signs/symptoms of pancreatitis; signs/symptoms of gallbladder disease.HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).Reference RangeRecommendations for glycemic control in patients with diabetes:Nonpregnant adults (ADA 2021):HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics).Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Older adults (≥65 years of age) (ADA 2021):Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).HbA1c: <7% to7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).Classification of hypoglycemia (ADA 2021):Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.Mechanism of ActionExenatide is an analog of the hormone incretin (glucagon-like peptide 1 or GLP-1) which increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth/replication, slows gastric emptying, and decreases food intake. Exenatide administration results in decreases in hemoglobin A1c by approximately 0.5% to 1% (immediate release) or 1.5% to 1.9% (extended release).Pharmaco*kineticsNote: In pediatric patients ≥11 years of age, pharmaco*kinetic parameters of the extended-release formulation were reported to be similar to adults.Distribution: Vd: 28.3 LMetabolism: Minimal systemic metabolism; proteolytic degradation may occur following glomerular filtrationHalf-life elimination:Immediate release (daily) formulation: 2.4 hoursExtended release (weekly) formulation: ~2 weeksTime to peak, plasma: SubQ:Immediate release (daily) formulation: 2.1 hoursExtended release (weekly) formulation: Single dose: Initial period of release of surface-bound exenatide is followed by a gradual release from microspheres with peaks at week 2 and week 6 to 7 respectively; with once-weekly dosing steady state is achieved at 6 to 7 weeks (Bydureon) and 10 weeks (Bydureon BCise).Excretion: Urine (majority of dose)Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: In patients with mild to moderate renal impairment, exposure to exenatide was increased compared with patients with normal renal function.Pricing: USAuto-injector (Bydureon BCise Subcutaneous)2MG/0.85ML (per 0.85 mL): $233.98Solution Pen-injector (Byetta 10 MCG Pen Subcutaneous)10 mcg/0.04 mL (per mL): $400.58Solution Pen-injector (Byetta 5 MCG Pen Subcutaneous)5 mcg/0.02 mL (per mL): $801.16Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalBaietta (CR, DO, GT, HN, MX, NI, PA, SV);Bydureon (AE, AT, AU, BE, BH, CH, CR, CZ, DE, DK, DO, EG, ES, GB, GT, HN, IE, IL, JP, KR, LB, LT, LU, LV, MT, MX, NI, NL, NO, NZ, PA, PL, SE, SG, SI, SK, SV);Bydureon BCise (AU);Byetta (AE, AT, AU, BB, BE, BG, BH, CH, CL, CN, CO, CY, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IS, IT, JO, JP, KR, KW, LT, LU, LV, MT, MY, NL, NO, NZ, PH, PK, PL, PT, QA, RO, RU, SA, SE, SI, SK, TH, TR, TW, ZA)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2018:84-103.Alexopoulos AS, Blair R, Peters AL. Management of preexisting diabetes in pregnancy: a review. JAMA. 2019;321(18):1811-1819. doi:10.1001/jama.2019.4981 [PubMed 31087027]American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi:10.1097/AOG.0000000000002960 [PubMed 30461693]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care.diabetesjournals.org/content/44/Supplement_1. Accessed January 13, 2021.Bethel MA, Mentz RJ, Merrill P, et al. Microvascular and cardiovascular outcomes according to renal function in patients treated with once-weekly exenatide: insights from the EXSCEL trial. Diabetes Care. 2020;43(2):446-452. doi:10.2337/dc19-1065 [PubMed 31757838]Blevins T, Pullman J, Malloy J, et al. DURATION-5: Exenatide Once Weekly Resulted in Greater Improvements in Glycemic Control Compared With Exenatide Twice Daily in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310. [PubMed21307137]Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617]Bydureon (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; January 2020.Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2022.Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2021.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2020.Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2021.Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.Byetta (exenatide) injection [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; November 2021.Byetta (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; December 2019.Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]DiMeglio LA, Acerini CL, Codner E, et al. ISPAD clinical practice consensus guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes. 2018;19(suppl 27):105-114. doi:10.1111/pedi.12737 [PubMed 30058221]Egan AM, Dow ML, Vella A. A review of the pathophysiology and management of diabetes in pregnancy. Mayo Clin Proc. 2020;95(12):2734-2746. doi:10.1016/j.mayocp.2020.02.019 [PubMed 32736942]Guja C, Frías JP, Suchower L, et al. Safety and efficacy of exenatide once weekly in participants with type 2 diabetes and stage 2/3 chronic kidney disease. Diabetes Ther. 2020;11(7):1467-1480. doi:10.1007/s13300-020-00815-z [PubMed 32306296]Hiles RA, Bawdon RE, Petrella EM. Ex vivo Human Placental Transfer of the Peptides Pramlintide and Exenatide (Synthetic Exendin-4). Hum Exp Toxicol. 2003;22(12):623-628. [PubMed 14992323]Holman RR, Bethel MA, Mentz RJ, et al; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228-1239. doi:10.1056/NEJMoa1612917 [PubMed 28910237]Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(supp 4):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]Kirkman M, Briscoe VJ, Clark N, et al. Diabetes in Older Adults: A Consensus Report. J Am Geriatr Soc. 2012. doi:10.1111/jgs.12035 [PubMed 23106132]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]Linnebjerg H, Seger M, Kothare PA, et al. A thorough QT study to evaluate the effects of single-dose exenatide 10 µg on cardiac repolarization in healthy subjects. Int J Clin Pharmacol Ther. 2011;49(10):594-604. [PubMed 21961484]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures -2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3(1):e001986. doi:10.1136/bmjopen-2012-001986 [PubMed 23355666]Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes. Diabetes Ther. 2019;10(1):5-19. doi:10.1007/s13300-018-0535-9 [PubMed 30506340]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed October 30, 2019.Wexler DJ. Initial management of blood glucose in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 14, 2020.Topic 9005 Version 287.0

Insulin lispro (conventional and faster-acting): Pediatric drug information

CloseInsulin lispro (conventional and faster-acting): Pediatric drug informationInsulin lispro (conventional and faster-acting): Pediatric drug information(For additional information see "Insulin lispro (conventional and faster-acting): Drug information" and see "Insulin lispro (conventional and faster-acting): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAdmelog;Admelog SoloStar;HumaLOG;HumaLOG Junior KwikPen;HumaLOG KwikPen;HumaLOG Tempo Pen;Lyumjev;Lyumjev KwikPen;Lyumjev Tempo PenBrand Names: CanadaAdmelog;Admelog SoloStar;HumaLOG Junior KwikPen;HumaLOG KwikPenTherapeutic CategoryAntidiabetic Agent, Parenteral;Insulin, Rapid-ActingDosing: PediatricInsulin lispro is a rapid-acting insulin analog available in a conventional formulation (eg, Admelog, Humalog) and an ultra-rapid formulation (Lyumjev), which differ in onset of action, administration instructions, and approved ages for use.Insulin doses should be individualized based on patient needs; adjustments may be necessary with changes in physical activity, meal patterns, acute illness, or with changes in renal or hepatic function. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.Type 1 diabetes mellitusType 1 diabetes mellitus: Children and Adolescents: Note: Insulin lispro is generally used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or via a continuous SubQ insulin infusion pump (Humalog U-100 and Admelog U-100 only). The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined.General insulin dosing:Initial total daily insulin: SubQ: Initial: 0.4 to 0.5 units/kg/day in divided doses (Ref) usual range: 0.4 to 1 units/kg/day in divided doses (Ref); lower doses (0.25 units/kg/day) may be used, especially in young children, to avoid potential hypoglycemia (Ref); higher doses may be necessary for some patients (eg, obese, concomitant steroids, puberty, sedentary lifestyle, following diabetic ketoacidosis presentation) (Ref).Usual total daily maintenance range: SubQ: Doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (Ref).Partial remission phase (Honeymoon phase): <0.5 units/kg/day.Prepubertal children (not in partial remission):Infants ≥6 months and Children ≤6 years: 0.4 to 0.8 units/kg/day.Children ≥7 years: 0.7 to 1 units/kg/day.Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day.Division of daily insulin requirement (multiple daily injections):Basal insulin: Generally, ~30% to 50% of the total daily insulin is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).Prandial insulin: The remaining portion of the total daily dose is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, aspart, glulisine, lispro) or short-acting (regular). In most type 1 patients, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (Ref).Dosage titration: Treatment and monitoring regimens must be individualized to maintain premeal and bedtime glucose in target range; titrate dose to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.Surgical patients (Ref): Note: Diabetic patients should be scheduled as the first case of the day.Minor surgeries:Morning procedure: Omit rapid-acting insulin (eg, aspart, glulisine, lispro) until after surgery and patient is able to eat unless it is needed to correct significant hyperglycemia and/or significant ketone (>0.1 mmol/mol) production is present.Afternoon procedure: If allowed to eat breakfast, administer the usual dose of rapid-acting insulin (eg, aspart, glulisine, lispro) with breakfast.Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to changes related to surgery (ie, postoperative stress, medication changes, inactivity).Major surgeries:Evening prior to surgery: Administer the usual evening and/or bedtime insulin(s); patients on continuous subcutaneous insulin infusion (CSII) may continue normal insulin basal rates overnight; if there is a concern for hypoglycemia, basal rate may be reduced by 20% at ~3 am.Morning of surgery: Omit morning insulin (short- and long-acting) and start IV insulin (regular) infusion and IV dextrose at least 2 hours prior to surgery; patients on CSII should discontinue CSII when IV insulin infusion is started.Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to changes related to surgery (ie, postoperative stress, medication changes, inactivity).Diabetic ketoacidosis, uncomplicatedDiabetic ketoacidosis (DKA), uncomplicated: Limited data available: Infants, Children, and Adolescents: SubQ: 0.15 units/kg/dose every 2 to 3 hours until resolution of metabolic acidosis (Ref); if serum glucose decreases by >100 mg/dL/hour, reduce dose to 0.1 units/kg/dose (Ref).Type 2 diabetes mellitusType 2 diabetes mellitus: Children ≥10 years and Adolescents: SubQ: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications. Initial therapy in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c >8.5%, symptoms excluding acidosis) may include once-daily intermediate-acting insulin or basal insulin in combination with lifestyle changes and metformin. In patients who fail to achieve glycemic goals with metformin and basal insulin, may consider initiating prandial insulin (regular insulin or rapid-acting insulin) and titrate to achieve goals. Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 10% to 30% every few days and the patient transitioned to lowest effective doses or metformin monotherapy if able (Ref). Note: Patients who are ketotic or present with ketoacidosis require aggressive management.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in manufacturer's labeling; insulin requirements are reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Adult(For additional information see "Insulin lispro (conventional and faster-acting): Drug information")Note: Insulin lispro is a rapid-acting insulin analog available in a conventional formulation (eg, Admelog, Humalog) and an ultra-rapid formulation (Lyumjev), which differ in onset of action and administration instructions (Ref). Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose. When switching between insulin lispro products, continue with the same insulin dose.Diabetes mellitus, type 1, treatmentDiabetes mellitus, type 1, treatment:Note: Insulin lispro must be used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or via a continuous SUBQ insulin infusion device (U-100 only). The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.General insulin dosing:Initial TDD: SUBQ: ~0.4 to 0.5 units/kg/day (Ref); conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid the potential for hypoglycemia; higher initial doses may be required in patients with obesity, or who are sedentary or presenting with ketoacidosis (Ref).Usual TDD maintenance range: SUBQ: 0.4 to 1 units/kg/day in divided doses (Ref).Division of TDD (multiple daily injections):Basal insulin: Generally, 40% to 50% of the TDD is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).Prandial insulin: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before, at, or just after mealtimes depending on the formulation (eg, short-, rapid-, ultra-rapid-acting) (Ref).Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: May be used if glycemic targets are not met despite adequately titrated basal insulin (eg, fasting glucose levels not at goal, basal insulin dose >0.5 units/kg/day) (Ref). For regimens containing basal and prandial insulin, consider discontinuing noninsulin agents other than metformin, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors (Ref).Initial:Note: Prandial insulin regimens are typically initiated as one daily injection administered before the largest meal; additional mealtime injections may be added based on results of glucose monitoring. In patients with HbA1c <8% when prandial insulin is initiated, consider reducing the basal insulin daily dose by 4 units/day or by 10% (Ref).SUBQ: 4 to 6 units or 10% of the basal insulin dose (Ref).Dosage adjustment: Note: Individualize dosage adjustments based on patient-specific factors (eg, glucose levels, carbohydrate intake) (Ref).For persistently elevated glucose levels: SUBQ: Consider intensification of dietary modifications and/or increasing the corresponding mealtime dose(s) by 1 to 2 units or by 10% to 15% every 3 days to achieve glycemic targets while avoiding hypoglycemia (Ref). Note: More aggressive dose increases (eg, by ≥5 units) may be required in patients already taking >20 units/dose of insulin lispro (Ref).For hypoglycemia: SUBQ: For unexplained mild to moderate hypoglycemia, consider decreasing the corresponding mealtime dose(s) by 10% to 20% (Ref); for hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing the corresponding mealtime dose(s) by 20% to 50% (Ref).Patients with diabetes receiving enteral feedingsPatients with diabetes receiving enteral feedings: Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).Nutritional: SUBQ: 1 unit of insulin lispro per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 4 hours based on the amount of carbohydrate administered over each 4-hour period (Ref).Correctional: SUBQ: Administer correctional insulin as needed prior to each feeding (for bolus feeds) or every 4 hours (for continuous feeds) (Ref). Dosing is individualized; one example of an empiric correctional dose is 1 to 2 units per 40 to 50 mg/dL above target glucose level; patients with known insulin resistance or who are receiving glucocorticoids may require higher correctional doses (eg, 4 units per 50 mg/dL above target glucose level) (Ref).Patients with diabetes undergoing surgery and using an insulin pumpPatients with diabetes undergoing surgery and using an insulin pump: SUBQ: For short procedures (eg, <2 hours), continue the usual pump "basal" insulin infusion rate, with or without a temporary 20% to 40% rate reduction, on the morning of the procedure. For long and complex procedures, consider transitioning from the insulin pump to an IV regular insulin infusion perioperatively (Ref).Diabetic ketoacidosis, mild to moderate, uncomplicatedDiabetic ketoacidosis, mild to moderate, uncomplicated (alternative agent) (off-label use):Note: SUBQ insulin lispro may be used as an alternative to IV regular insulin in patients in whom management of diabetic ketoacidosis (DKA) outside of a critical care area is appropriate; faster-acting insulin lispro products (eg, Lyumjev) have not been evaluated for this purpose. IV regular insulin (preferred over IV rapid-acting insulin analogs) should be used in patients with severe DKA, evidence of hyperosmolar hyperglycemic state (eg, altered mental status), persistent hypotension, or other critical illness, as well as during pregnancy (Ref). Begin correction of fluid deficits, if present. If serum potassium is <3.3 mEq/L on initial presentation, delay insulin administration until serum potassium reaches ≥3.3 mEq/L. Address other electrolyte abnormalities, as needed, during insulin administration (Kitabchi 2009). In patients with initial serum glucose <250 mg/dL, initiate dextrose-containing IV fluids at the time of insulin initiation (Ref). An example of a dosing regimen is as follows; refer to institutional protocols:1-hour interval dosing: SUBQ: 0.3 units/kg once, followed by 0.1 units/kg every hour until blood glucose <250 mg/dL, then decrease to 0.05 units/kg every hour until resolution of ketoacidosis (Ref). May increase dose (eg, by double) if serum glucose does not decrease by ~50 to 75 mg/dL in the first hour (Ref).2-hour interval dosing: SUBQ: 0.3 units/kg once, followed by 0.2 units/kg 1 hour later and then every 2 hours thereafter until blood glucose <250 mg/dL, then decrease to 0.1 units/kg every 2 hours until resolution of ketoacidosis. May increase dose (eg, by double) if serum glucose does not decrease by ~50 to 75 mg/dL in the first hour (Ref).Hyperglycemia, hospitalized patientsHyperglycemia, hospitalized patients (off-label use):Note: For use in patients with persistent hyperglycemia (eg, blood glucose ≥140 to 180 mg/dL for >12 to 24 hours) with or without a history of diabetes; use of institution-specific protocols to achieve glycemic targets and minimize hypoglycemia is encouraged (Ref).Correctional insulin:Note: For use in addition to scheduled basal and nutritional insulin to achieve glycemic targets; prolonged use of correctional insulin without basal insulin is discouraged (Ref).SUBQ: Refer to institution-specific protocols; one example of an empiric correctional dose is 1 to 2 units per 40 to 50 mg/dL above target glucose level; dose is typically administered with meals (or bolus feeds) or every 4 hours (if NPO or receiving continuous feeds); patients with known insulin resistance or who are receiving glucocorticoids may require higher correctional doses (eg, 4 units per 50 mg/dL above target glucose level) (Ref).Nutritional insulin:Initial daily dosage:Patients not receiving nutritional insulin prior to hospitalization:Patients eating meals: SUBQ: 0.03 to 0.1 units/kg/meal administered with or just after meals (Ref). Note: Dose is individualized; consider doses at the lower end of this range in older patients and in those with renal impairment; consider doses at the higher end of this range in patients receiving glucocorticoids (Ref).Patients receiving enteral feeds: SUBQ: 1 unit of insulin lispro per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 4 hours based on the amount of carbohydrate administered over each 4-hour period (Ref).Patients receiving nutritional insulin prior to hospitalization: SUBQ: Continue the pre-hospitalization nutritional insulin dose; an empiric 25 to 50% dose reduction may be considered in patients with impaired renal function, poor nutritional intake, or admission glucose levels <100 mg/dL; higher doses may be required in patients receiving glucocorticoids (Ref).Dosage adjustment: Adjust daily dose by 10% to 20% every 2 to 3 days to achieve glycemic targets. Consider reducing dosage for glucose levels <100 mg/dL to avoid hypoglycemia; in patients with glucose levels <40 mg/dL, larger dose reductions (eg, by 20% to 40%) may be needed (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism.Dosing: Hepatic Impairment: AdultThere are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Injection: Admelog: 100 units/mL (3 mL, 10 mL) [contains metacresol]HumaLOG: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]Lyumjev: Insulin lispro-aabc 100 unit/mL (10 mL) [contains metacresol]Generic: 100 units/mL (10 mL)Solution, Subcutaneous: HumaLOG: 100 units/mL (3 mL) [contains metacresol, phenol]Solution Pen-injector, Subcutaneous: Admelog SoloStar: 100 units/mL (3 mL) [contains metacresol]HumaLOG Junior KwikPen: 100 units/mL (3 mL) [contains metacresol, phenol]HumaLOG KwikPen: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]HumaLOG Tempo Pen: 100 units/mL (3 mL) [contains metacresol, phenol]Lyumjev KwikPen: Insulin lispro-aabc 100 unit/mL (3 mL); Insulin lispro-aabc 200 unit/mL (3 mL) [contains metacresol]Lyumjev Tempo Pen: Insulin lispro-aabc 100 units/mL (3 mL) [contains metacresol]Generic: 100 units/mL (3 mL)Generic Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Injection: Admelog: 100 units/mL (10 mL) [contains metacresol]Solution Cartridge, Subcutaneous: Admelog: 100 units/mL (3 mL) [contains metacresol]Solution Pen-injector, Subcutaneous: Admelog SoloStar: 100 units/mL (3 mL) [contains metacresol]HumaLOG Junior KwikPen: 100 units/mL (3 mL) [contains metacresol]HumaLOG KwikPen: 200 units/mL (3 mL) [contains metacresol]Dosage Forms ConsiderationsHumalog Tempo Pen: The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.Lyumjev Tempo Pen: The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.Product AvailabilityHumalog Tempo Pen: FDA approved November 2019; anticipated availability is currently unknown. Information pertaining to this product within the monograph is pending revision. The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.Administration: PediatricParenteral: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles.SUBQ: Avoid cold injections. Administer into the subcutaneous fat of the thighs, arms, buttocks, or abdomen. Rotate injection sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.Humalog: Administer within 15 minutes before or immediately after a meal. Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. Do not mix insulin lispro U-200 (200 units/mL) with any other insulin.Vial: Humalog U-100 (100 units/mL) from a vial may be mixed only with insulin NPH (do not mix with other types of insulin); insulin lispro should be drawn into syringe first. Use immediately after mixing.Prefilled pens: Humalog prefilled pens are available in concentrations of 100 units/mL and 200 units/mL. Devices are designed to display the actual insulin units administered (no dosage conversion needed) and will administer up to 30 units per injection in 0.5-unit increments (U-100 Junior KwikPen) or up to 60 units per injection in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen). Do not transfer insulin lispro U-200 to a syringe for administration; markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia. For all Humalog prefilled pen devices, prime the needle before each injection with 2 units of insulin (use a new needle for each injection); see manufacturer's labeling for specific procedure. Once primed, set dial to the appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose dial has returned to 0 units. After the insulin is injected, hold the needle in the skin for 5 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered. Do not rub the area. If dose is >30 units (U-100 Junior KwikPen) or >60 units (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen), >1 injection will be required; split dose and administer in multiple injections.Admelog: Admelog SoloStar prefilled pen will administer up to 80 units per injection in 1-unit increments. Prior to each injection, the needle must be primed with 2 units of insulin (use a new needle for each injection); see manufacturer's labeling for specific procedure. Once primed, set dial to the appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose dial has returned to 0 units. After the insulin is injected, hold the needle in the skin for 10 seconds after the dose dial has returned to 0 units to ensure the full dose has been administered. Do not rub the area. If dose is >80 units, >1 injection will be required; split dose and administer in multiple injections. Do not mix other insulin formulations with insulin lispro contained in a prefilled pen.Continuous SUBQ insulin infusion (Insulin pump): Admelog and Humalog only: Insulin lispro U-100 (100 units/mL) may be administered via inulin pumps; do not administer insulin lispro U-200 (200 units/mL) via insulin pumps. Do not use if solution is viscous or cloudy; use only if clear and colorless. Patients should be trained in the proper use of their external insulin pump and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed every 3 days; rotate infusion sites. Insulin in reservoir should be changed every 7 days or according to insulin pump user manual (whichever is shorter). Do not dilute or mix other insulin formulations with insulin lispro contained in an external insulin pump.IV: Insulin lispro U-100 (100 units/mL) may be administered IV in selected clinical situations to control hyperglycemia. Closely monitor blood glucose and serum potassium; appropriate medical supervision is required. Further dilute with NS prior to administration. Do not administer insulin mixtures intravenously.To minimize adsorption to IV tubing: At low concentrations and flow rates, insulin lispro has been shown to adsorb to PVC IV bags and tubing (Ref). Therefore, flush the IV tubing with a priming volume of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (Ref). Also refer to institution-specific protocols where appropriate.Because of adsorption, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SUBQ dosing regimen (Ref); however, the transition to SUBQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. Transition to a protocol-driven basal/bolus insulin regimen should begin prior to stopping the IV infusion in order to avoid significant loss of glucose control (Ref).Administration: AdultUse only if solution is clear and colorless; do not use if solution contains particulate matter or is colored.SUBQ administration: Cold injections should be avoided. SUBQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.Admelog: Administer within 15 minutes before or immediately after a meal. Do not mix with any other insulin. For Admelog SoloStar pen, prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for ~10 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.Humalog: Administer within 15 minutes before or immediately after a meal. Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. Do not mix insulin lispro U-200 (200 units/mL) with any other insulin. May mix insulin lispro U-100 (100 units/mL) from a vial only with insulin NPH (do not mix with other types of insulin); insulin lispro should be drawn into syringe first; perform injection immediately. Prefilled pen devices are designed to dial doses in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen) or in 0.5-unit increments (U-100 Junior KwikPen). Do not perform dose conversion when using Humalog prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U-200 to a syringe for administration. For Humalog prefilled pen devices, prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for ~5 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.Lyumjev: Administer at the start of a meal or within 20 minutes after starting a meal; routine postprandial use should be avoided due to reduced efficacy vs mealtime administration (Klaff 2020). Do not mix with any other insulin. Prefilled pen devices are designed to dial doses in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen) or in 0.5-unit increments (U-100 Junior KwikPen). Do not perform dose conversion when using prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U-200 to a syringe for administration. For Lyumjev prefilled pen devices, prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for ~5 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.Continuous SUBQ insulin infusion administration: Insulin lispro U-100 (100 units/mL) may be administered via continuous SUBQ insulin infusion (CSII) device (ie, insulin pump); do not administer insulin lispro U-200 (200 units/mL) via a CSII device. Patients should be trained in the proper use of their CSII device and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed every 3 days; rotate infusion sites. Insulin in reservoir should be changed at least every 7 days (Admelog, Humalog), 9 days (Lyumjev), or according to CSII device user manual (whichever is shorter). Do not dilute or mix other insulins with insulin lispro U-100 that is to be used in a CSII device.IV administration: Insulin lispro U-100 (100 units/mL) may be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin lispro U-200 (200 units/mL) IV. Do not administer insulin mixtures IV.IV infusions: To minimize adsorption to IV tubing: At low concentrations and flow rates, insulin lispro has been shown to adsorb to PVC IV bags and tubing (Ling 1999). Therefore, flush the IV tubing with a priming infusion of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (Ref).Note: Also refer to institution-specific protocols where appropriate.Because of insulin adsorption to IV tubing or infusion bags, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SUBQ dosing regimen (Ref); however, the transition to SUBQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. Transition to a protocol-driven basal/bolus insulin regimen should begin prior to stopping the IV infusion in order to avoid significant loss of glucose control (Ref).Storage/StabilityUnopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date or at room temperature <30°C (<86°F) for 28 days; do not freeze; keep away from heat and light. Once punctured (in use), vials may be stored under refrigeration or at room temperature <30°C (<86°F); use within 28 days. Cartridges and prefilled pens that have been punctured (in use) should be stored at room temperatures <30°C (<86°F) and used within 28 days; do not freeze or refrigerate. When used via a continuous SUBQ insulin infusion device, insulin lispro contained within an external insulin pump reservoir should be changed every 7 days (Admelog, Humalog) or 9 days (Lyumjev) and insulin lispro contained within a 3 mL cartridge should be discarded after 7 days; discard if exposed to temperatures >37°C (>98.6°F).Diluted solution for SUBQ administration:Humalog: After dilution may store at 30°C (86°F) for 14 days or at 5°C (41°F) for 28 days.Admelog: After dilution may store at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at 30°C (86°F) for up to 4 hours.Diluted solution for IV infusion:Humalog: Stable in NS for 48 hours when stored under refrigeration between 2°C and 8°C (36°F to 46°F); may then be used at room temperature for an additional 48 hours.Admelog: Stable in NS for 24 hours when stored at 2°C to 8°C (36°F to 46°F) or for up to 4 hours room temperature.Lyumjev: Stable in NS or D5W for up to 4 days when stored under refrigeration between 2°C and 8°C (36°F to 46°F) or for up to 12 hours at room temperature.UseImprovement of glycemic control in patients with type 1 diabetes mellitus (Admelog, Humalog: FDA approved in ages ≥3 years and adults; Lyumjev: FDA approved in adults); improvement of glycemic control in patients with type 2 diabetes mellitus (Admelog, Humalog, Lyumjev: FDA approved in adults); has also been used for the treatment of diabetic ketoacidosis (DKA).Medication Safety IssuesSound-alike/look-alike issues:HumaLOG may be confused with HumaLOG Mix 50/50, Humira, HumuLIN N, HumuLIN R, NovoLOGHumapen Memoir (used with HumaLOG) may be confused with the Humira PenHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type and strength of insulin to be used.Older Adult: High-Risk Medication:Beers Criteria: Insulin (short- or rapid-acting insulin products used for sliding scale) is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to higher risk of hypoglycemia associated with sliding scale insulin without improvements in hyperglycemia, regardless of care setting. Avoid insulin regimens that only use short- or rapid-acting insulins dosed based on current blood glucose levels in the absence of basal or long-acting insulin; recommendation does not apply to regimens containing basal or long-acting insulin (Beers Criteria [AGS 2019]).Other safety concerns:Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics and may include concomitant basal insulin.>10%:Endocrine & metabolic: Severe hypoglycemia (≤14%)Immunologic: Antibody development (19% to 33%)Local: Infusion-site reaction (3% to 38%; includes infusion-site pain [16%])Nervous system: Headache, painRespiratory: Cough, flu-like symptoms, nasopharyngitis (5% to 15%), pharyngitis, rhinitis1% to 10%:Dermatologic: Pruritus (≤1%)Gastrointestinal: Abdominal pain, diarrhea, nauseaLocal: Injection-site reaction (3% to 6%, may be secondary to excipient; including bruising at injection site, erythema at injection site, inflammation at injection site, injection-site pruritus, pain at injection site, rash at injection site)Nervous system: AstheniaNeuromuscular & skeletal: Myalgia (may be secondary to excipient)Respiratory: Bronchitis, upper respiratory tract infection (1% to 7%)<1%:Cardiovascular: Peripheral edemaHypersensitivity: Hypersensitivity reactionLocal: Hypertrophy at injection site, lipoatrophy at injection siteFrequency not defined: Endocrine & metabolic: Hypokalemia, weight gainPostmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous)ContraindicationsHypersensitivity to insulin lispro or any component of the formulation; during episodes of hypoglycemia.Warnings/PrecautionsConcerns related to adverse effects:• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content or timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long standing diabetes, diabetic nerve disease, patients taking beta-blockers or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.• Hypersensitivity: Hypersensitivity reactions (serious, life-threatening and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium frequently with IV insulin use and supplement potassium when necessary.Disease-related concerns:• Bariatric surgery:– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of ≥75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs), may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced, and patients may require more frequent dose adjustment and glucose monitoring.• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced, and patients may require more frequent dose adjustment and glucose monitoring.Special populations:• Hospitalized patients: Prolonged use of a sliding scale insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin use is preferred, with correctional doses (insulin regular or rapid-acting insulin) as needed. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin along with nutritional and correctional components (insulin regular or rapid-acting insulin) is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2022).Dosage form specific issues: • Prefilled pen devices: Do not perform dose conversion when using prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro from a prefilled pen to a syringe.• Multiple-dose injection pens: According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• CSII administration: Insulin lispro U-100 (100 units/mL) may be administered via a CSII device; do not dilute or mix with other insulins. Rule out external pump failure if unexplained hyperglycemia or ketosis occurs; temporary SUBQ insulin administration may be required until the problem is identified and corrected. Insulin lispro U-200 (200 units/mL) is not indicated for use in a CSII device.• IV administration: Insulin lispro U-100 (100 units/mL) may be administered IV in selected clinical situations to control hyperglycemia; close monitoring of blood glucose and serum potassium as well as medical supervision is required. Insulin lispro U-200 (200 units/mL) is not indicated for IV administration.• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAlpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationAlpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyAntidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEdetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGlucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHerbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyLiraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modificationMacimorelin: Insulins may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMetreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin.Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modificationPramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modificationProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyRosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination.Risk X: Avoid combinationSalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDietary ConsiderationsIndividualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.Reproductive ConsiderationsPatients with diabetes mellitus who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2022).Insulin lispro is one of the preferred insulins for use in patients with diabetes mellitus planning to become pregnant (Blumer 2013).Pregnancy ConsiderationsInsulin lispro has not been shown to cross the placenta at standard clinical doses (Boskovic 2003; Holcberg 2004; Jovanovic 1999).Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2022; Blumer 2013).Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2022).Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2022). Insulin lispro is one of the preferred insulins for use in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).Monitoring ParametersSerum glucose, electrolytes, HbA1c (every 3 months; if patient is stable and meeting treatment goals, may only need twice-yearly testing; unstable patients on intensive therapy [eg, pregnancy] may need more frequent testing) (ADA 2020), renal function (at diagnosis and at least annually) (ADA [Chiang 2014]), hepatic function.Reference RangePlasma Blood Glucose and HbA1c Goals for Diabetes Patients: Note: Postprandial blood glucose should be measured when there is a discrepancy between preprandial blood glucose concentrations and HbA1c values and to help assess glycemia for patients who receive basal/bolus or pump regimens. It is usually drawn 1 to 2 hours after starting a meal and is considered to be the "peak."Infants, Children, and Adolescents:Preprandial glucose: 70 to 130 mg/dL (ISPAD [DiMeglio 2018]).Postprandial glucose: 90 to 180 mg/dL (ISPAD [DiMeglio 2018]).Bedtime/overnight glucose: 80 to 140 mg/dL (ISPAD [DiMeglio 2018]).HbA1c: <7%; Target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, or have extensive comorbid conditions (ADA 2020; ISPAD [DiMeglio 2018]).Surgical patients (ISPAD [Jefferies 2018]):Intraoperative: 90 to 180 mg/dL.ICU, postsurgery: 140 to 180 mg/dL.Adults, nonpregnant (ADA 2020):Preprandial glucose: 80 to 130 mg/dL.Postprandial glucose: <180 mg/dL.HbA1c: <7%.Mechanism of ActionInsulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Insulin stimulates lipoprotein lipase synthesis and activity; this results in hydrolysis of triglycerides into free fatty acids and storage of free fatty acids in adipocytes, thereby reducing circulating triglyceride levels (Rawla 2018; Sadur 1982; Song 2019). In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin lispro differs from human insulin by containing a lysine and proline at positions B28 and B29, respectively, in comparison to the proline and lysine found at B28 and B29 in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin lispro is a rapid-acting insulin analog.Pharmaco*kinetics (Adult data unless noted)Note: Onset and duration of hypoglycemic effects depend upon the route of administration, site of injection (onset and duration are progressively slower with SUBQ injection into the abdomen, arm, buttock, or thigh respectively), volume and concentration of injection, and the preparation administered. Rate of absorption, onset, and duration of activity may be affected by exercise, presence of lipodystrophy, local blood supply, and/or temperature. Insulin lispro is available in multiple formulations. Humalog and Admelog are highly similar (Kapitza 2017); Lyumjev formulation contains unique excipients (treprostinil and citrate) that facilitate more rapid SUBQ absorption (Leohr 2020; Linnebjerg 2020).Onset of action: SUBQ:Admelog: Similar onset to Humalog (Kapitza 2017).Humalog: 31 minutes (patients with type 1 diabetes) (Linnebjerg 2020); 45 minutes (patients with type 2 diabetes) (Leohr 2020).Lyumjev: ~15 to 17 minutes (manufacturer's labeling); 20.1 minutes (patients with type 1 diabetes) (Linnebjerg 2020); 32 minutes (patients with type 2 diabetes) (Leohr 2020).Peak effect:Admelog: ~2.1 hours.Humalog: 2.4 to 2.8 hours.Lyumjev: ~2 to 2.9 hours.Duration: SUBQ:Admelog: ~6.9 hours (patients with type 1 diabetes) (Kapitza 2017).Humalog: ~5.7 to 6.6 hours (patients with type 1 diabetes) (Kapitza 2017; Linnebjerg 2020); ~6.7 hours (patients with type 2 diabetes) (Leohr 2020).Lyumjev: ~4.6 to 7.3 hours (manufacturer's labeling); ~5 hours (patients with type 1 diabetes) (Linnebjerg 2020); ~6.4 hours (patients with type 2 diabetes) (Leohr 2020).Distribution: Vd: IV: Humalog: 0.72 to 1.55 L/kg (inversely related to dose); Lyumjev: 34 L.Bioavailability: SUBQ: Admelog, Humalog: 55% to 77%; Lyumjev: 65%.Half-life elimination: Admelog, Humalog: 51 to 60 minutes; Lyumjev: 44 minutes.Time to peak, plasma: SUBQ:Admelog, Humalog: Median: ~50 minutes (Kapitza 2017; manufacturer's labeling [Admelog]); range: 30 to 90 minutes (manufacturer's labeling [Humalog]).Lyumjev: 57 minutes; time to reach 50% of peak plasma concentration was 14 minutes shorter compared to Humalog in patients with type 1 diabetes (14.8 vs 29 minutes, respectively) (Linnebjerg 2020) and 11 minutes shorter compared to Humalog in patients with type 2 diabetes (18.6 vs 29.6 minutes respectively) (Leohr 2020).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Insulin clearance may be reduced in patients with impaired renal function.Pricing: USSolution (Admelog Injection)100 units/mL (per mL): $15.69Solution (HumaLOG Injection)100 units/mL (per mL): $32.96Solution (Insulin Lispro Injection)100 units/mL (per mL): $9.89Solution (Lyumjev Injection)100 units/mL (per mL): $32.96Solution Cartridge (HumaLOG Subcutaneous)100 units/mL (per mL): $40.84Solution Pen-injector (Admelog SoloStar Subcutaneous)100 units/mL (per mL): $15.15Solution Pen-injector (HumaLOG Junior KwikPen Subcutaneous)100 units/mL (per mL): $42.43Solution Pen-injector (HumaLOG KwikPen Subcutaneous)100 units/mL (per mL): $42.43200 units/mL (per mL): $84.86Solution Pen-injector (HumaLOG Tempo Pen Subcutaneous)100 units/mL (per mL): $42.43Solution Pen-injector (Insulin Lispro (1 Unit Dial) Subcutaneous)100 units/mL (per mL): $12.73Solution Pen-injector (Lyumjev KwikPen Subcutaneous)100 units/mL (per mL): $42.43200 units/mL (per mL): $84.86Solution Pen-injector (Lyumjev Tempo Pen Subcutaneous)100 units/mL (per mL): $42.43Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalHumalog (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CY, CZ, DE, DK, ES, ET, FI, FR, GB, GH, GM, GN, GR, GY, HN, HR, HU, IE, IN, IS, IT, JM, JP, KE, KW, LB, LK, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, NE, NG, NL, NO, PK, PT, PY, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, TH, TN, TR, TT, TW, TZ, UG, UY, VE, VN, ZA, ZM, ZW);Humalog Lispro (CR, GT, HN, IL, KR, NI, PA, PE, SV);Humalog Miriopen (JP);Humalog Mix NPL (AT, BE, BG, CH, CZ, DE, DK, FI, FR, GB, GR, HN, IE, IT, NO, PT, RU, SE, TR);Humaloh (UA);Insul Lispro (BD);Insulin Humalog (PL);Insuline Lispro Humalog (FR);Liprolog (AT, BE, BG, CH, CZ, DE, DK, FI, FR, GB, GR, HN, IE, IT, NO, PT, RU, SE, TR)For country code abbreviations (show table)2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767. [PubMed 30693946]Admelog (insulin lispro) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; December 2020.American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960. [PubMed 30461693]American Diabetes Association (ADA). 11. Older Adults: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018b;41(suppl 1):S119-S125. doi:10.2337/dc18-S011 [PubMed 29222382]American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.American Diabetes Association (ADA). Standards of medical care in diabetes–2022. Diabetes Care. 2022;45(suppl 1):S1-S255. https://diabetesjournals.org/care/issue/45/Supplement_1. Accessed September 19, 2022.Anderson PO. Treating diabetes during breastfeeding. Breastfeed Med. 2018;13(4):237-239. doi:10.1089/bfm.2018.0036 [PubMed 29608329]Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(5):2135-2136]. J Clin Endocrinol Metab. 2015;100(2):342-362. doi: 10.1210/jc.2014-3415. [PubMed 25590212]Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care. 2018;41(12):2648-2668. [PubMed 30425094]Beck JK, Cogen FR. Outpatient management of pediatric type 1 diabetes. J Pediatr Pharmacol Ther. 2015;20(5):344-357. doi: 10.5863/1551-6776-20.5.344. [PubMed 26472948]Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617 ]Boskovic R, Feig DS, Derewlany L, et al. Transfer of insulin lispro across the human placenta: In vitro perfusion studies. Diabetes Care. 2003; 26(5):1390-1394. [PubMed 12716794]Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012. [PubMed 22111719]Cardoso L, Vicente N, Rodrigues D, Gomes L, Carrilho F. Controversies in the management of hyperglycaemic emergencies in adults with diabetes. Metabolism. 2017;68:43-54. doi:10.1016/j.metabol.2016.11.010 [PubMed 28183452]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Chiang JL, Kirkman MS, Laffel LM, et al; Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-2054. doi:10.2337/dc14-1140 [PubMed 24935775]Clement S, Braithwaite SS, Magee MF, et al; American Diabetes Association Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591. doi:10.2337/diacare.27.2.553 [PubMed 14747243]Copeland KC, Silverstein J, Moore KR, et al; American Academy of Pediatrics. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382. doi: 10.1542/peds.2012-3494. [PubMed 23359574]Cruijsen M, Koehestani P, Huttjes S, Leenders K, Janssen I, de Boer H. Perioperative glycaemic control in insulin-treated type 2 diabetes patients undergoing gastric bypass surgery. Neth J Med. 2014;72(4):202-209. [PubMed 24829176]Danne T, Phillip M, Buckingham BA, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes. 2018;19(suppl 27):115-135. doi: 10.1111/pedi.12718. [PubMed 29999222]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]DiMeglio LA, Acerini CL, Codner E, et al. ISPAD clinical practice consensus guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes. 2018;19(suppl 27):105-114. doi:10.1111/pedi.12737 [PubMed 30058221]Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. doi:10.4158/CS-2019-0472 [PubMed 32022600]Gianchandani RY, Iyengar JL, Butler SO, et al. Inpatient diabetes guideline for adult non-critically ill patients. Michigan Medicine, University of Michigan; May 2020. [PubMed 32931166]Goldberg PA, Kedves A, Walter K, et al, "'Waste Not, Want Not': Determining the Optimal Priming Volume for Intravenous Insulin Infusions," Diabetes Technol Ther, 2006, 8(5):598-601. [PubMed 17037974]Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21(suppl 1):1-87. https://journals.aace.com/doi/pdf/10.4158/EP15672.GLSUPPL. Accessed April 23, 2020. doi:10.4158/EP15672.GL.Hirsch IB. Evidence-based priming. Diabetes Technol Ther. 2006;8(5):521-522.Hirsch IB, Emmett M. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed September 27, 2021.Holcberg G, Tsadkin-Tamir M, Sapir O, et al. Transfer of insulin lispro across the human placenta. Eur J Obstet Gynecol Reprod Biol. 2004; 115(1):117-118. [PubMed 15223182]Humalog (insulin lispro injection [rDNA origin] solution) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; November 2019.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-149. [PubMed 25538310]Inzucchi SE. Diabetes facts and guidelines. https://medicine.yale.edu/intmed/drc/diabetescenter/living/50135_Yale%20National%20F_102165_284_13584_v1.pdf. Published 2011. Accessed January 12, 2021.Jacobi J, Bircher N, Krinsley J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med. 2012;40(12):3251-3276. [PubMed 23164767]Jefferies C, Rhodes E, Rachmiel M, et al. ISPAD clinical practice consensus guidelines 2018: management of children and adolescents with diabetes requiring surgery. Pediatr Diabetes. 2018;19(suppl 27):227-236. doi:10.1111/pedi.12733 [PubMed 30039617]Jovanovic L, Ilic S, Pettitt DJ, et al. Metabolic and immunologic effects of insulin lispro in gestational diabetes. Diabetes Care. 1999;22(9):1422-1427. [PubMed 10480503]Kapitza C, Nowotny I, Lehmann A, et al. Similar pharmaco*kinetics and pharmacodynamics of rapid-acting insulin lispro products SAR342434 and US- and EU-approved Humalog in subjects with type 1 diabetes. Diabetes Obes Metab. 2017;19(5):622-627. doi:10.1111/dom.12856 [PubMed 27987252]Kidney Disease: Improving Global Outcomes (KDIGO) diabetes work group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]Kirkman M, Briscoe VJ, Clark N, et al. Diabetes in older adults: A consensus report. J Am Geriatr Soc. 2012; doi: 10.1111/jgs.12035. [PubMed 23106132]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. [PubMed 19564476]Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: results from the 26-week PRONTO-T1D study. Diabetes Obes Metab. Published online June 2, 2020. doi:10.1111/dom.14100 [PubMed 32488923]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]Leohr J, Dellva MA, Coutant DE, et al. Pharmaco*kinetics and glucodynamics of ultra rapid lispro (URLi) versus Humalog (lispro) in patients with type 2 diabetes mellitus: a phase I randomised, crossover study. Clin Pharmaco*kinet. Published online May 29, 2020. doi:10.1007/s40262-020-00901-2 [PubMed 32468448]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]Leung V, Ragbir-Toolsie K. Perioperative management of patients with diabetes [published online November 15, 2017]. Health Serv Insights. doi:10.1177/1178632917735075 [PubMed 29162977]Ling J, Hu M, Hagerup T, et al. Lispro insulin: adsorption and stability in selected intravenous devices. Diabetes Educ. 1999;25(2):237-245. [PubMed 10531849]Linnebjerg H, Zhang Q, LaBell E, et al. Pharmaco*kinetics and glucodynamics of ultra rapid lispro (URLi) versus Humalog (lispro) in younger adults and elderly patients with type 1 diabetes mellitus: a randomised controlled trial. Clin Pharmaco*kinet. Published online May 29, 2020. doi:10.1007/s40262-020-00903-0 [PubMed 32468447]Lyumjev (insulin lispro-aabc injection) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; October 2022.Magaji V, Johnston JM. Inpatient management of hyperglycemia and diabetes. Clinical Diabetes. 2011;29(1):3-9. doi:10.2337/diaclin.29.1.3Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.Endocr Pract. 2009;15(4):353-369. [PubMed 19454396]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Peters AP, Laffel L, eds. Type 1 Diabetes Sourcebook. American Diabetes Association; 2013.Rawla P, Sunkara T, Thandra KC, Gaduputi V. Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies. Clin J Gastroenterol. 2018;11(6):441-448. doi:10.1007/s12328-018-0881-1 [PubMed 29923163]Rawla P, Vellipuram AR, Bandaru SS, Pradeep Raj J. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep. 2017;2017:17-0081. doi:10.1530/EDM-17-0081 [PubMed 28924481]Reader D, Franz MJ. Lactation, diabetes, and nutrition recommendations. Curr Diab Rep. 2004;4(5):370-376. [PubMed 15461903]Sadur CN, Eckel RH. Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique. J Clin Invest. 1982;69(5):1119-1125. doi:10.1172/jci110547 [PubMed 7040473]Savoldelli RD, Farhat SC, Manna TD. Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department. Diabetol Metab Syndr. 2010;2:41. [PubMed 20550713]Silverstein J, Klingensmith G, Copeland K, et al. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186-212. [PubMed 15616254]Song X, Shi D, Cui Q, et al. Intensive insulin therapy versus plasmapheresis in the management of hypertriglyceridemia-induced acute pancreatitis (Bi-TPAI trial): study protocol for a randomized controlled trial. Trials. 2019;20(1):365. doi:10.1186/s13063-019-3498-x [PubMed 31215460]Sundberg F, Barnard K, Cato A, et al. ISPAD Guidelines. Managing diabetes in preschool children. Pediatr Diabetes. 2017;18(7):499-517. doi: 10.1111/pedi.12554 [PubMed 28726299]Thompson CD, Vital-Carona J, Faustino EV. The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions. Diabetes Technol Ther. 2012;14(10):912-916. [PubMed 22746979]Umpierrez GE, Cuervo R, Karabell A, et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004; 27(8):1873-1878. [PubMed 15277410]Umpierrez GE, Hellman R, Korytkowski MT, et al; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16-38. doi:10.1210/jc.2011-2098 [PubMed 22223765]Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117(5):291-296. [PubMed 15336577]Wexler DJ. COVID-19: issues related to diabetes mellitus in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed September 27, 2021.Wexler DJ. Insulin therapy in type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed September 19, 2022.Whitmore TJ, Trengove NJ, Graham DF, Hartmann PE. Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:296368. [PubMed 22500167]Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19(Suppl 27):155–177. [PubMed 29900641]Zeitler P, Arslanian S, Fu J, Pinhas-Hamiel O, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Type 2 diabetes mellitus in youth. Pediatr Diabetes. 2018;19(suppl 27):28-46. doi: 10.1111/pedi.12719. [PubMed 29999228]Topic 12772 Version 282.0

Teriparatide (including biosimilars available in Canada): Drug information

CloseTeriparatide (including biosimilars available in Canada): Drug informationTeriparatide (including biosimilars available in Canada): Drug information(For additional information see "Teriparatide (including biosimilars available in Canada): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USForteoBrand Names: CanadaForteo;TEVA-TeriparatidePharmacologic CategoryParathyroid Hormone AnalogDosing: AdultNote: Assess serum calcium prior to initiation; avoid use in patients with preexisting hypercalcemia or hypercalcemic disorder. Correct vitamin D deficiency (eg, to a 25-hydroxyvitamin D level ≥20 ng/mL [≥50 nmol/L]) prior to initiating therapy and ensure adequate calcium and vitamin D intake during therapy; however, use caution to avoid hypercalcemia (ES [Eastell 2019]; Licata 2005; NAMS 2021; Rosen 2021; manufacturer’s labeling).Osteoporosis, glucocorticoid inducedOsteoporosis, glucocorticoid induced (alternative agent): Note: Alternative agent if bisphosphonate therapy is not appropriate. Avoid use in women who are pregnant, who plan on becoming pregnant, or who are not using effective birth control (ACR [Buckley 2017]).SUBQ: 20 mcg once daily.Osteoporosis, fracture risk reductionOsteoporosis, fracture risk reduction (males and postmenopausal females): Note: For use as initial therapy in patients with very high fracture risk, including those with a T-score less than –3, a T-score less than –2.5 with fragility fracture history, or severe or multiple prior vertebral fractures. May also be used as an alternative agent in patients with high fracture risk in whom first-line therapies are ineffective or cannot be used (AACE/ACE [Camacho 2020]; ES [Eastell 2019]). Prior to use, evaluate and treat any potential causes of secondary osteoporosis (eg, severe vitamin D deficiency) (NOF [Cosman 2014]).SUBQ: 20 mcg once daily.Duration of therapy: Duration of teriparatide therapy should generally not exceed 2 years due to limited data with use beyond this; fracture reduction efficacy has been demonstrated over a period of 18 to 24 months (Geusens 2018; Neer 2001; manufacturer’s labeling).Discontinuation/interruption of therapy: Following a course of teriparatide, switch to antiresorptive therapy (eg, with a bisphosphonate or denosumab) to maintain bone density gains (ES [Eastell 2019]).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultNo dosage adjustment necessary.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Forteo: 600 mcg/2.4 mL (2.4 mL) [contains metacresol]Generic: 620 mcg/2.48 mL (2.48 mL)Generic Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Forteo: 750 mcg/3 mL (3 mL) [contains metacresol]Generic: 600 mcg/2.4 mL (2.4 mL)Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021318Orig1s054lbl.pdf#page=16, must be dispensed with this medication.Administration: AdultSUBQ: Initial administration should occur under circ*mstances in which the patient may sit or lie down, in the event of orthostasis.Inject into the thigh or abdominal wall. Administer without regard to meals or time of day. May administer dose immediately following removal from the refrigerator. Each teriparatide delivery device can be used for up to 28 days after the first injection. Note: The 3 mL prefilled pen [Canadian product] must be primed prior to each dose.Use: Labeled IndicationsOsteoporosis: Treatment of osteoporosis in postmenopausal females who are at high risk for fracture (defined as history of osteoporotic fracture or multiple risk factors for fracture); treatment to increase bone mass in males with primary or hypogonadal osteoporosis who are high risk for fracture; treatment of males and females with glucocorticoid-induced osteoporosis associated with chronic systemic glucocorticoids with a prednisone dosage of ≥5 mg/day (or equivalent) at a high risk for fracture. May also be used in patients who have failed or are intolerant to other available osteoporosis therapy.Limitations of use: Cumulative lifetime duration of teriparatide beyond 2 years should only be considered if a patient remains at or has returned to having a high risk of fracture.Note: In Canada, Osnuvo is approved as a biosimilar to Forteo.Medication Safety IssuesSound-alike/look-alike issues: Forteo may be confused with Forfivo XLAdverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%:Endocrine & metabolic: Hypercalcemia (females: 11%; males: 6%; transient increases noted 4 to 6 hours postdose)Gastrointestinal: Nausea (9% to 14%)1% to 10%:Cardiovascular: Angina pectoris (3%), orthostatic hypotension (5%; transient), syncope (3%)Endocrine & metabolic: Hyperuricemia (3%)Gastrointestinal: Dyspepsia (5%), gastritis (7%), vomiting (3%)Immunologic: Antibody development (3% of women in long-term treatment; hypersensitivity reactions or decreased efficacy were not associated in preclinical trials)Infection: Herpes zoster (3%)Nervous system: Anxiety (4%), depression (4%), dizziness (8%), headache (8%), insomnia (5%), vertigo (4%)Neuromuscular & skeletal: Arthralgia (10%), asthenia (9%), lower limb cramp (3%)Respiratory: Dyspnea (4% to 6%; including acute dyspnea), pharyngitis (6%), pneumonia (3% to 6%), rhinitis (10%)Postmarketing:Cardiovascular: Chest pain, facial edemaDermatologic: Cutaneous calcification (including calciphylaxis and exacerbation of cutaneous calcification), urticariaEndocrine & metabolic: Hypercalcemia (>13 mg/dL)Hematologic & oncologic: OsteosarcomaHypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction, mouth edemaLocal: Injection site reaction (including bruising at injection site, pain at injection site, swelling at injection site)Neuromuscular & skeletal: Muscle spasmContraindicationsHypersensitivity (eg, anaphylaxis, angioedema) to teriparatide or any component of the formulation.Canadian labeling: Additional contraindications (not in US labeling): Preexisting hypercalcemia; severe renal impairment; metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget disease of the bone); unexplained elevations of alkaline phosphatase; prior external beam or implant radiation therapy involving the skeleton; bone metastases or history of skeletal malignancies; pregnancy; breastfeeding; pediatric patients or young adults with open epiphysis.Warnings/PrecautionsConcerns related to adverse effects:• Cutaneous calcification: Serious worsening of previous stable cutaneous calcification or calciphylaxis has been reported; discontinue use if occurs. Patients with underlying autoimmune disease, kidney failure, or concomitantly taking warfarin or systemic corticosteroids are at increased risk.• Orthostatic hypotension: May cause orthostatic hypotension. Transient orthostatic hypotension usually occurs within 4 hours of dosing and within the first several doses; usually resolved without treatment within a few minutes to a few hours.• Osteosarcoma: In animal studies, teriparatide has been associated with an increase in osteosarcoma. Human cases have been reported in postmarketing; increased risk has not been seen in observational studies. Avoid use in patients with an increased risk of osteosarcoma (including Paget disease, bone metastases or a history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, hereditary disorders predisposing to osteosarcoma, or in patients with open epiphyses).Disease-related concerns:• Hypercalcemia: Use with caution in patients with hypercalcemia (not studied); may increase or exacerbate hypercalcemia. Avoid use in patients with known or history of hypercalcemia disorder (eg, primary hyperparathyroidism).• Urolithiasis: Use with caution in patients with active or recent urolithiasis because of risk of exacerbation.Dosage form specific issues:• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Metabolism/Transport EffectsNone known.Drug InteractionsThere are no known significant interactions.Pregnancy ConsiderationsAdverse events were observed in animal reproduction studies; consider discontinuing treatment once pregnancy is recognized.Breastfeeding ConsiderationsIt is not known if teriparatide is present in breast milk.The manufacturer recommends avoiding use in patients who are breastfeeding.Dietary ConsiderationsEnsure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Patients should consume:Calcium: 1,000 mg/day (males: 50 to 70 years of age) or 1,200 mg/day (females ≥51 years of age and males ≥71 years of age) (IOM 2011; NOF [Cosman 2014]). Some clinicians have suggested limiting calcium to ≤1,000 mg/day in patients taking teriparatide (Licata 2005).Vitamin D: 800 to 1,000 units/day (age ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 units/day (age ≤70 years) or 800 units/day (age ≥71 years) (IOM 2011).Monitoring ParametersOrthostatic hypotension; serum calcium (draw at least 16 hours after teriparatide dose); urinary calcium (patients with suspected active urolithiasis or preexisting hypercalciuria).Bone mineral density (BMD) should be evaluated at baseline and ~1 to 2 years following initiation of therapy) (AACE/ACE [Camacho 2020]; ES [Eastell 2019]; NOF [Cosman 2014]); may consider monitoring biochemical markers of bone turnover (eg, serum P1NP) at baseline, 3 months, and 6 months to assess treatment response (ES [Eastell 2019]; Miller 2016).Mechanism of ActionTeriparatide is a recombinant formulation of endogenous parathyroid hormone (PTH), containing a 34-amino-acid sequence which is identical to the N-terminal portion of this hormone. The pharmacologic activity of teriparatide, which is similar to the physiologic activity of PTH, includes stimulating osteoblast function, increasing gastrointestinal calcium absorption, and increasing renal tubular reabsorption of calcium. Treatment with teriparatide results in increased bone mineral density, bone mass, and strength. In postmenopausal females, teriparatide has been shown to decrease osteoporosis-related fractures.Pharmaco*kineticsDistribution: Vd: ~0.12 L/kg.Metabolism: Hepatic (nonspecific proteolysis).Bioavailability: ~95%.Half-life elimination: IV: 5 minutes; SubQ: ~1 hour.Time to peak, serum: ~30 minutes.Excretion: Urine (as metabolites).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: In patients with severe renal impairment (CrCl less than 30 mL/min), the AUC and half-life increased 73% and 77%, respectively. Maximum serum concentration was not increased.Sex: Systemic exposure is approximately 20% to 30% lower in males.Pricing: USSolution Pen-injector (Forteo Subcutaneous)600 mcg/2.4 mL (per mL): $1,983.30Solution Pen-injector (Teriparatide (Recombinant) Subcutaneous)620MCG/2.48ML (per mL): $1,197.58Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalForsteo (AT, BE, BG, CH, CN, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, KR, LT, LU, LV, MT, NL, NO, PL, PT, RO, RU, SE, SI, SK, TR);Forteo (AE, AR, AU, BB, BH, BR, CL, CO, HK, HR, JP, KW, LB, LK, MX, MY, NZ, PE, PH, PY, QA, SA, SG, TH, TW, VE);Forteo Colter (CR, DO, GT, HN, NI, PA, SV);Human PTH (JP);Mega PTH (TH);Movymia (AT, BE, CZ, DE, DK, EE, ES, FR, HR, HU, IE, LT, LV, NL, PT, SK);Osteofortil (AR);Teribone (JP, KR);Terrosa (AT, BE, CZ, DE, DK, EE, ES, HR, HU, LT, LV, NL, PT, SK)For country code abbreviations (show table)Body JJ, Gaich GA, Scheele WH, et al. A Randomized Double-blind Trial to Compare the Efficacy of Teriparatide [Recombinant Human Parathyroid Hormone (1-34)] With Alendronate in Postmenopausal Women With Osteoporosis. J Clin Endocrinol Metab. 2002;87(10):4528-4535. [PubMed 12364430]Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 2017;69(8):1521-1537. doi:10.1002/art.40137 [PubMed 28585373]Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis–2020 update. Endocr Pract. 2020;26(suppl 1):1-46. doi:10.4158/GL-2020-0524SUPPL [PubMed 27643923]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381. doi:10.1007/s00198-014-2794-2 [PubMed 25182228]Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1595-1622. doi:10.1210/jc.2019-00221 [PubMed 30907953]Forteo (teriparatide) [prescribing information]. Indianapolis, IN: Lilly USA LLC; September 2021.Forteo (teriparatide) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; August 2021.Geusens P, Marin F, Kendler DL, et al. Effects of teriparatide compared with risedronate on the risk of fractures in subgroups of postmenopausal women with severe osteoporosis: the VERO Trial. J Bone Miner Res. 2018;33(5):783-794. doi:10.1002/jbmr.3384 [PubMed 29329484]IOM (Institute of Medicine). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2011.Licata AA. Osteoporosis, teriparatide, and dosing of calcium and vitamin D. N Engl J Med. 2005;352(18):1930-1931. doi:10.1056/NEJM200505053521822 [PubMed 15872215]Miller PD, Hattersley G, Riis BJ, et al; ACTIVE Study Investigators. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722-733. doi:10.1001/jama.2016.11136 [PubMed 27533157]Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women With Osteoporosis. N Engl J Med. 2001;344(19):1434-1441. [PubMed 11346808]North American Menopause Society. Management of osteoporosis in postmenopausal women: the 2021 position statement of the North American Menopause Society. Menopause. 2021;28(9):973-997. doi:10.1097/GME.0000000000001831 [PubMed 34448749]Osnuvo (teriparatide) [product monograph]. Blainville, Quebec, Canada: AVIR Pharma Inc; March 2022.Reeve J. Recombinant Human Parathyroid Hormone. BMJ. 2002;324(7335):435-436. [PubMed 11859030]Rosen HN, Drezner MK. Overview of the management of osteoporosis in postmenopausal women. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 4, 2021.Saag KG, Shane E, Boonen S, et al. Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis. N Engl J Med. 2007;357(20):2028-2039. [PubMed 18003959]Topic 10178 Version 168.0

Benralizumab: Pediatric drug information

CloseBenralizumab: Pediatric drug informationBenralizumab: Pediatric drug information(For additional information see "Benralizumab: Drug information" and see "Benralizumab: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USFasenra;Fasenra PenBrand Names: CanadaFasenra;Fasenra PenTherapeutic CategoryInterleukin-5 Receptor Antagonist;Monoclonal Antibody, Anti-AsthmaticDosing: PediatricAsthma, eosinophilic phenotype; add-on maintenance therapyAsthma, eosinophilic phenotype; add-on maintenance therapy: Children ≥12 years and Adolescents: SubQ: 30 mg every 4 weeks for the first 3 doses then once every 8 weeksDosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on renal function is unlikely to be necessary as benralizumab is not renally cleared.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on hepatic function is unlikely to be necessary as benralizumab is degraded by widely distributed proteolytic enzymes that are not restricted to hepatic tissue.Dosing: Adult(For additional information see "Benralizumab: Drug information")Asthma, severe eosinophilicAsthma, severe eosinophilic: Note: May consider as add-on therapy in patients with severe eosinophilic asthma (peripheral blood eosinophils ≥150 cells/mcL) inadequately controlled on standard therapies (eg, an inhaled glucocorticoid with a long-acting beta agonist). The eosinophil threshold required for patients on systemic glucocorticoids is less clear (GINA 2022).SUBQ: 30 mg every 4 weeks for the first 3 doses, then once every 8 weeks. A minimum of 4 months of treatment is suggested to determine efficacy (GINA 2022).Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on renal function is unlikely to be necessary as benralizumab is not renally cleared.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment based on hepatic function is unlikely to be necessary as benralizumab is degraded by widely distributed proteolytic enzymes that are not restricted to hepatic tissue.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Auto-injector, Subcutaneous [preservative free]: Fasenra Pen: 30 mg/mL (1 mL)Solution Prefilled Syringe, Subcutaneous [preservative free]: Fasenra: 30 mg/mL (1 mL)Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Auto-injector, Subcutaneous: Fasenra Pen: 30 mg/mL (1 mL)Solution Prefilled Syringe, Subcutaneous: Fasenra: 30 mg/mL (1 mL)Administration: PediatricSubQ: May be administered undiluted subcutaneously into the upper arm, thigh, or abdomen. Do not inject within 2 inches of the belly button or within 1 inch of last injection. Prior to administration, allow prefilled syringe or autoinjector to warm at room temperature for about 30 minutes. Solution is clear to opalescent, colorless to slight yellow liquid; particles may be present in the solution that appear translucent or white to off-white; do not use if cloudy or discolored. Syringe or autoinjector may contain a small air bubble; do not expel the air bubble prior to administration. Prefilled syringe should only be administered by a health care provider; autoinjector may be administered by patient or caregiver after proper training. Patients should not self-inject into the arm.Administration: AdultSUBQ: Prior to administration, allow syringe/autoinjector to warm at room temperature for ~30 minutes. Administer SubQ into the upper arm, thigh, or abdomen. Prefilled syringe should only be administered by a health care provider; autoinjector may be administered by patient or caregiver after proper training. Refer to the manufacturer's labeling for additional administration instructions.Storage/StabilityStore in original carton at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. May be stored at room temperature (≤25°C [77°F]) in original carton for ≤14 days.UseTreatment of severe asthma with an eosinophilic phenotype as add-on maintenance therapy (FDA approved in ages ≥12 years and adults). Note: Not indicated for treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%: Immunologic: Antibody development (13%; neutralizing: 12%)1% to 10%:Central nervous system: Headache (8%)Respiratory: Pharyngitis (5%)Miscellaneous: Fever (3%)Postmarketing: Anaphylaxis, angioedema, hypersensitivity reactionContraindicationsHypersensitivity to benralizumab or any component of the formulationWarnings/PrecautionsConcerns related to adverse effects:• Hypersensitivity: Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) may occur, typically within hours of administration. Delayed hypersensitivity reactions, occurring days after administration, have also been reported. Discontinue use in patients who experience a hypersensitivity reaction.Disease-related concerns:• Asthma: Not indicated for the treatment of acute asthma symptoms (eg, acute bronchospasm) or acute exacerbations, including status asthmaticus.• Helminth infections: It is unknown if administration of benralizumab will influence a patient's immune response against parasitic infections. Therefore, patients with preexisting helminth infections should undergo treatment of the infection prior to initiation of benralizumab therapy. Patients who become infected during benralizumab treatment and do not respond to antihelminth therapy should discontinue benralizumab until the infection resolves.Other warnings/precautions:• Corticosteroids: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of benralizumab. Reductions in corticosteroid dose should be gradual, if appropriate. Clinicians should note that a reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programEfgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapyReproductive ConsiderationsData related to the use of monoclonal antibodies for the treatment of asthma in pregnancy is limited. The long half-life of monoclonal antibodies should be considered when prescribing to patients planning to become pregnant (Pfaller 2021).Pregnancy ConsiderationsBenralizumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).Outcome data following maternal use of benralizumab during pregnancy are limited (Manetz 2021; Saco 2018).Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low-birth-weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2022).Use of monoclonal antibodies for the treatment of asthma in pregnancy may be considered when conventional therapies are insufficient; use of an agent other than benralizumab may be preferred (ERS/TSANZ [Middleton 2020]).Data collection to monitor pregnancy and infant outcomes following exposure to benralizumab is ongoing. Health care providers are encouraged to enroll exposed pregnant patients in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS) (877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.Monitoring ParametersAnaphylaxis/hypersensitivity reactions; peak flow and/or other pulmonary function tests; monitor for signs of infectionMechanism of ActionBenralizumab, a humanized afucosylated, monoclonal antibody (IgG1, kappa) that binds to the alpha subunit of the interleukin-5 receptor. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils (a cell type associated with inflammation and an important component in the pathogenesis of asthma). Benralizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils and basophils through antibody dependent cell-mediated cytotoxicity; however, the mechanism of benralizumab action in asthma has not been definitively established.Pharmaco*kinetics (Adult data unless noted)Note: Pharmaco*kinetic data in pediatric patients 12 to 17 years of age is similar to adult observationsDistribution: 3.1 L (central); 2.5 L (peripheral)Metabolism: Undergoes proteolytic degradation via enzymes that are widely distributed in the body and not restricted to hepatic tissue.Bioavailability: ~59%Half-life elimination: ~15.5 daysExcretion: NonrenalPricing: USSolution Auto-injector (Fasenra Pen Subcutaneous)30 mg/mL (per mL): $6,421.06Solution Prefilled Syringe (Fasenra Subcutaneous)30 mg/mL (per mL): $6,421.06Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalFasenra (AT, AU, BE, CH, CZ, DE, DK, EE, ES, FI, GB, HK, HR, IL, LT, LV, NL, NO, NZ, PL, PT, SE, SG, TW);Fasenra Pen (AU);Fasnera (RO)For country code abbreviations (show table)Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med. 2021;16(8):591-593. doi:10.1089/bfm.2021.0110 [PubMed 33956488]Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]Fasenra (benralizumab) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2021.Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention.https://ginasthma.org/gina-reports/. Updated 2022. Accessed October 11, 2022.Manetz S, Maric I, Brown T, et al. Successful pregnancy in the setting of eosinophil depletion by benralizumab. J Allergy Clin Immunol Pract. 2021;9(3):1405-1407.e3. doi:10.1016/j.jaip.2020.11.060 [PubMed 33316460]Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ Task Force statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2):1901208. doi: 10.1183/13993003.01208-2019 [PubMed 31699837]Nair P, Wenzel S, Rabe KF, et al; ZONDA Trial Investigators. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448-2458. doi:10.1056/NEJMoa1703501 [PubMed 28530840]Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]Pfaller B, José Yepes-Nuñez J, Agache I, et al. Biologicals in atopic disease in pregnancy: an EAACI position paper. Allergy. 2021;76(1):71-89. doi:10.1111/all.14282 [PubMed 32189356]Saco T, Tabatabaian F. Breathing for two: a case of severe eosinophilic asthma during pregnancy treated with benralizumab. Ann Allergy Asthma Immunol. 2018;121(5 suppl):S92. https://www.annallergy.org/article/S1081-1206(18)31046-9/pdf.Topic 117810 Version 49.0

Insulin degludec: Drug information

CloseInsulin degludec: Drug informationInsulin degludec: Drug information(For additional information see "Insulin degludec: Patient drug information" and see "Insulin degludec: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USTresiba;Tresiba FlexTouchBrand Names: CanadaTresibaPharmacologic CategoryInsulin, Long-ActingDosing: AdultNote: Insulin degludec is a basal insulin. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.Diabetes mellitus, type 1, treatmentDiabetes mellitus, type 1, treatment:Note: Insulin degludec must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injections regimen). The total daily doses (TDDs) presented below are expressed as the total units/kg/day of all insulin formulations (basal and prandial) combined.General insulin dosing:Initial TDD: SUBQ: 0.4 to 0.5 units/kg/day; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid hypoglycemia (AACE/ACE [Handelsman 2015]; ADA 2022).Usual TDD maintenance range: SUBQ: 0.4 to 1 units/kg/day in divided doses (ADA 2022).Division of TDD (multiple daily injections):Basal insulin: SUBQ: 40% to 50% of the TDD administered as insulin degludec once daily (AACE/ACE [Handelsman 2015]; ADA 2022).Prandial insulin: SUBQ: The remaining portion (ie, 50% to 60%) of the TDD is divided and administered before, at, or just after mealtimes, depending on the formulation (AACE/ACE [Handelsman 2015]; ADA 2022).Dosage adjustment for glycemic control: SUBQ: Increase or decrease daily dose by 10% to 20% once or twice weekly (eg, every 3 or 7 days) to maintain premeal and bedtime glucose in target range; avoid more frequent dosage adjustment to minimize hypoglycemia risk (ADA 2022; McCall 2012).Preoperative dosage adjustment:Once-daily evening administration: SUBQ: Reduce insulin degludec dose by 10% to 25% the evening before the procedure; may administer the full dose in patients whose glucose levels are generally elevated (eg, >200 mg/dL) (ES [Umpierrez 2012]; Khan 2022).Once-daily morning administration: SUBQ: Administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin degludec the morning of the procedure (Khan 2022).Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: Preferred in patients with symptomatic hyperglycemia (eg, weight loss, polydipsia, polyuria) or ketonuria; may also be used in patients with severe hyperglycemia (eg, fasting glucose >250 mg/dL, random glucose consistently >300 mg/dL, HbA1c >9%), or if glycemic goals are not met despite adequately titrated metformin with or without other noninsulin agents (ADA 2022; Wexler 2022a). Consider discontinuation or a dose reduction of sulfonylureas and thiazolidinediones when initiating basal insulin therapy (ADA/EASD [Davies 2018]).Initial: SUBQ: 10 units once daily or 0.1 to 0.2 units/kg once daily (ADA 2022; manufacturer’s labeling). In patients with HbA1c >8%, fasting plasma glucose >250 mg/dL, or insulin resistance, 0.2 to 0.3 units/kg/day is recommended (AACE/ACE [Garber 2020]; Wexler 2022b). Some experts use a minimum of 10 units/day and do not exceed 20 units/day for the initial dose (Wexler 2022b).Dosage adjustment:For persistently elevated fasting plasma glucose: SUBQ: Increase daily dose by 2 to 4 units or by 10% to 20% every 3 to 7 days to achieve fasting plasma glucose target while avoiding hypoglycemia (AACE/ACE [Garber 2020]; ADA 2022; Rosenstock 2018; Wexler 2022b).For elevated HbA1c despite achieving fasting plasma glucose target: SUBQ: Encourage lifestyle modifications. Consider adding other medications (eg, a glucagon-like peptide-1 receptor agonist or prandial insulin before the largest meal). In some patients, higher insulin degludec doses (eg, >0.5 units/kg/day) may provide diminishing additional improvements in HbA1c (AACE/ACE [Garber 2020]; ADA 2022).For hypoglycemia: SUBQ: For unexplained mild to moderate hypoglycemia, consider decreasing daily dose by 10% to 20% (ADA 2022); for severe hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing daily dose by 20% to 50% (AACE/ACE [Garber 2020]; Wexler 2022b).Dosage adjustment when adding prandial insulin: SUBQ: In patients whose glucose levels are close to target (eg, HbA1c <8%), consider decreasing the basal insulin daily dose by 4 units or by 10% (ADA 2022).Preoperative dosage adjustment:Evening dosage adjustment: SUBQ: Reduce insulin degludec dose by 10% to 25% the evening before the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL) (ES [Umpierrez 2012]; Khan 2022).Morning dosage adjustment: SUBQ: For patients not using prandial insulin, reduce insulin degludec dose by 10% to 25% the morning of the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL). For patients using prandial insulin, omit prandial insulin after fasting begins and administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin degludec the morning of the procedure (ES [Umpierrez 2012]; Khan 2022).Conversion from other basal insulins to insulin degludec: SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis; in patients taking twice-daily basal insulin (eg, with insulin NPH or detemir), may consider a 10% to 20% dose reduction when converting to once-daily insulin degludec if hypoglycemia is a concern (Wexler 2022b).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Pediatric(For additional information see "Insulin degludec: Pediatric drug information")The general objective of insulin replacement therapy is to approximate the physiologic pattern of insulin secretion. This requires a basal level of insulin throughout the day, supplemented by additional insulin at mealtimes. Since combinations using different types of insulins are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. The frequency of doses and monitoring must be individualized in consideration of the patient's ability to manage therapy.Insulin degludec is a long-acting insulin administered by SubQ injection. When compared to insulin regular, insulin degludec has a slower onset and a longer duration of activity. Changing the basal insulin component from another insulin to insulin degludec requires a dose reduction to minimize the risk of hypoglycemia. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision.Note: U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen.Type 1 diabetes mellitusType 1 diabetes mellitus: Children and Adolescents: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations used. Insulin degludec must be used in combination with a short-acting insulin.General insulin dosing:Usual maintenance range: SubQ: 0.5 to 1 unit/kg/day in divided doses; doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (ISPAD [Couper 2014]; ISPAD [Danne 2014])Partial remission phase (Honeymoon phase): <0.5 units/kg/dayPrepubertal children (not in partial remission): 0.7 to 1 units/kg/dayPubescent Children and Adolescents: During puberty, requirements may substantially increase to >1.2 unit/kg/day and in some cases up to 2 units/kg/day Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the daily insulin dose is given as an intermediate- or long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the 24-hour insulin requirement is divided and administered as either regular insulin or a rapid-acting form of insulin at the same time before breakfast and dinner.Division of daily insulin requirement ("intensive therapy"): Basal insulin delivery with 1 or 2 doses of intermediate- or long-acting insulin formulations superimposed with doses of rapid- or very rapid-acting insulin formulations 3 or more times dailyAdjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.Insulin degludec-specific dosing: Children and Adolescents: SubQ: Note: Not recommended for patients requiring less than 5 units of insulin degludec.Insulin-naive patients: Approximately one-third to one-half of the total daily insulin requirement administered as insulin degludec once daily; remainder of total daily dose should be given as a short- or rapid-acting insulin and divided between each daily meal (general rule for initial total daily insulin dose: 0.2 to 0.4 units/kg/day).Insulin-experienced patients: Initiate insulin degludec at 80% of the total daily long- or intermediate-acting insulin unit dose from which the patient is being converted.Dosage adjustment: Individualize and titrate dose every 3 to 4 days based on patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal.Type 2 diabetes mellitusType 2 diabetes mellitus: Children ≥10 years and Adolescents: Note: Not recommended for patients requiring less than 5 units of insulin degludec.General insulin dosing: SubQ: The goal of therapy is to achieve an HbA1c <6.5% as quickly as possible using the safe titration of medications. Initial therapy in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c >9% and symptoms excluding acidosis) may include once daily intermediate acting insulin or basal insulin in combination with lifestyle changes and metformin. In patients who fail to achieve glycemic goals with metformin and basal insulin, may consider initiating prandial insulin (regular insulin or rapid acting insulin) and titrate to achieve goals. Once initial goal reached, insulin should be slowly tapered and the patient transitioned to lowest effective doses or metformin monotherapy if able (AAP [Copeland 2013]; ISPAD [Zeitler 2014]). Note: Patients who are ketotic or present with ketoacidosis require aggressive management as indicated.Insulin degludec-specific dosing: Note: Not recommended for patients requiring less than 5 units of insulin degludec.Insulin-naive patients: Initial: 10 units once dailyInsulin-experienced patients: Initiate insulin degludec at 80% of the total daily long- or intermediate-acting insulin unit dose from which the patient is being convertedDosage adjustment: Individualize and titrate dose every 3 to 4 days based on patient’s metabolic needs, blood glucose monitoring results, and glycemic control goalDosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Subcutaneous: Tresiba: 100 units/mL (10 mL) [contains metacresol, phenol]Generic: 100 units/mL (10 mL)Solution Pen-injector, Subcutaneous: Tresiba FlexTouch: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]Generic: 100 units/mL (3 mL); 200 units/mL (3 mL)Generic Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Tresiba: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]Administration: AdultSubcutaneous: For subcutaneous administration into the thigh, upper arm, or abdomen; do not administer IM or IV, or in an insulin infusion pump. Absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Insulin degludec should be administered once daily at any time of the day. Multidose vials should be used in patients requiring <5 units per day.FlexTouch pens: Do not perform dose conversion when using the FlexTouch pen. The dose window for both U-100 and U-200 FlexTouch pens show the number of insulin units to be delivered and no conversion is needed. U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen. Do not dilute or mix insulin degludec with any other insulin formulation or solution; do not transfer from the FlexTouch pen into a syringe for administration. For both U-100 and U-200 FlexTouch pens, prime the needle before each injection with 2 units of insulin (use a new needle for each injection). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 6 seconds. Then, remove the needle.Vials: Administer using U-100 insulin syringes.Administration: PediatricParenteral: SubQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Administer subcutaneously into the thigh, upper arm, or abdomen, with sites rotated to decrease the risk of lipodystrophy; do not administer IM or IV, or in an insulin infusion pump. Administer once daily, at any time of day, but at the same time each day in pediatric patients. In adults, insulin degludec should be administered once daily at any time of the day. Do not dilute or mix insulin degludec with any other insulin formulation or solution; do not transfer from the FlexTouch pen into a syringe for administration. Do not perform dose conversion when using the FlexTouch pen. The dose window for both U-100 and U-200 FlexTouch pens show the number of insulin units to be delivered and no conversion is needed. U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen. For both U-100 and U-200 FlexTouch pens, prime the needle before each injection with 2 units of insulin (use a new needle for each injection). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 6 seconds. Then, remove the needle.Use: Labeled IndicationsDiabetes mellitus, types 1 and 2, treatment: To improve glycemic control in patients ≥1 year of age with type 1 or type 2 diabetes mellitus.Medication Safety IssuesSound-alike/look-alike issues:Tresiba may be confused with Tanzeum [DSC], Tarceva, Toujeo, Tradjenta, TrulicityHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes insulins among its classes of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.Administration issues:Insulin degludec is a clear solution, but it is NOT intended for IV or IM administration.U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should be prescribed the U-100 FlexTouch pen or U-100 multidose vials.Other safety concerns:Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%:Endocrine & metabolic: Severe hypoglycemia (type 1 diabetics on combination insulin therapy: 10% to 18%; type 2 diabetics on combination therapy: ≤5%)Immunologic: Antibody developmentNervous system: Headache (9% to 12%)Respiratory: Nasopharyngitis (13% to 24%), upper respiratory tract infection (8% to 12%)1% to 10%:Cardiovascular: Peripheral edema (type 2 diabetes: 3%; type 1 diabetes: <1%)Gastrointestinal: Diarrhea (type 2 diabetes: 6%), gastroenteritis (type 1 diabetes: 5%)Local: Injection site reaction (4%)Respiratory: Sinusitis (type 1 diabetes: 5%)<1%:Dermatologic: UrticariaHypersensitivity: Hypersensitivity reactionLocal: Hypertrophy at injection site (lipohypertrophy), lipoatrophy at injection site, lipotrophy at injection site (lipodystrophy)Frequency not defined: Endocrine & metabolic: Hypokalemia, weight gainPostmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)ContraindicationsHypersensitivity to insulin degludec or any component of the formulation; during episodes of hypoglycemiaDocumentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Warnings/PrecautionsConcerns related to adverse effects:• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic nerve disease, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.• Hypersensitivity: Severe, life-threatening allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.Disease-related concerns:• Bariatric surgery:– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2019). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. Rates and timing of type 2 diabetes improvement and resolution vary widely by patient; insulin dose reduction of 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014).– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.• Diabetic ketoacidosis: Should not be used in patients with diabetic ketoacidosis; use of a rapid-acting or short-acting insulin is required.• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.Special populations:• Hospitalized patients: Prolonged use of a sliding scale insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin use is preferred, with correctional doses (insulin regular or rapid-acting insulin) as needed. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin along with nutritional and correctional components (insulin regular or rapid-acting insulin) is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2022).• Obesity: A decrease in glucose lowering effect of insulin degludec with increasing BMI has been observed.Dosage form specific issues:• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Administration: Insulin degludec is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationAlpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyAntidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEdetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGlucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHerbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyLiraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modificationMacimorelin: Insulins may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMetreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin.Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modificationPramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modificationProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyRosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination.Risk X: Avoid combinationSalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyReproductive ConsiderationsEffective contraception is recommended for all patients under management for diabetes mellitus who could become pregnant, including those immediately postpartum. Pregnancy should be planned when optimal glycemic control is achieved (ADA 2022).Pregnancy ConsiderationsInsulin degludec can be detected in cord blood.Based on available data, an increased risk of adverse pregnancy outcomes has not been observed following the use of insulin degludec in pregnant patients (Bonora 2018; Hiranput 2019; Keller 2019; Ringholm 2022).Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2022; Blumer 2013).Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2022). Due to the long half-life and duration of action of insulin degludec, omitting the first dose after delivery may help decrease the risk of maternal hypoglycemia immediately postpartum (Keller 2019).Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed. However, insulin degludec is not currently recommended to treat diabetes mellitus in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).Breastfeeding ConsiderationsBoth exogenous and endogenous insulin are present in breast milk (study not conducted with this preparation) (Whitmore 2012). Insulin is not systemically absorbed via breast milk but may provide local benefits to the infant GI tract (Anderson 2018).Appropriate glycemic control is required for the establishment of lactation in patients with diabetes mellitus (Anderson 2018). Breastfeeding provides metabolic benefits to mothers with type 1, type 2, and gestational diabetes mellitus as well as their infants; therefore, breastfeeding is encouraged (ACOG 201 2018; ADA 2022; Blumer 2013). Breastfeeding also influences maternal glucose tolerance and may increase the risk of overnight hypoglycemia; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2022; Anderson 2018). A small snack before breastfeeding may help decrease the risk of hypoglycemia in patients with pregestational diabetes (ACOG 201 2018; Reader 2004). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.Dietary ConsiderationsIndividualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.Monitoring ParametersDiabetes mellitus: Blood glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2022); electrolytes; renal function; hepatic function; weight.Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 2018).Hospitalized patients: In patients who are eating, monitor blood glucose before meals and at bedtime; in patients who are not eating or are receiving continuous enteral feeds, monitor blood glucose every 4 to 6 hours (ADA 2022; ES [Umpierrez 2012]). More frequent monitoring may be required in some cases (eg, recurrent hypoglycemia, changes in nutrition, medication changes affecting glycemic control) (ES [Umpierrez 2012]).HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2022; KDIGO 2020).Reference RangeRecommendations for glycemic control in patients with diabetes:Nonpregnant adults (ADA 2022):HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Older adults (≥65 years of age) (ADA 2022):Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).Pregnant patients:HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2022):Preconception (patients planning for pregnancy): <6.5%.During pregnancy <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2022).Gestational diabetes mellitus (ACOG 2018; ADA 2022):Fasting: <95 mg/dL.Postprandial: <140 mg/dL (at 1 hour) or <120 mg/dL (at 2 hours).Pregestational diabetes mellitus (type 1 or type 2) (ADA 2022):Fasting: 70 to 95 mg/dL.Postprandial: 110 to 140 mg/dL (at 1 hour) or 100 to 120 mg/dL (at 2 hours).Hospitalized adult patients (ADA 2022): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia). Initiate insulin therapy for persistent hyperglycemia at ≥180 mg/dL.Perioperative care in adult patients (ADA 2022): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL.Children and adolescents:Preprandial glucose: 70 to 130 mg/dL (ISPAD [Dimeglio 2018]).Postprandial glucose: 90 to 180 mg/dL (ISPAD [Dimeglio 2018]).Bedtime/overnight glucose: 80 to 140 mg/dL (ISPAD [Dimeglio 2018]).HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, or have extensive comorbid conditions (ADA 2022; ISPAD [Dimeglio 2018]).Surgical patients (ISPAD [Jefferies 2018]):Intraoperative: 90 to 180 mg/dL.ICU, postsurgery: 140 to 180 mg/dL.Classification of hypoglycemia (ADA 2022):Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.Mechanism of ActionInsulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin degludec differs from human insulin by the omission of the amino acid threonine in position B-30 of the B-chain, and the subsequent addition of a side chain composed of glutamic acid and a C16 fatty acid. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin degludec is a long-acting, human insulin analog.Pharmaco*kineticsNote: Rate of absorption, onset, and duration of activity may be affected by site of injection, exercise, presence of lipodystrophy, local blood supply, and/or temperature.Onset: ~1 hourProtein binding: >99% (albumin)Half-life elimination: ~25 hours (independent of dose)Time to peak: 9 hoursPricing: USSolution (Insulin Degludec Subcutaneous)100 units/mL (per mL): $14.24Solution (Tresiba Subcutaneous)100 units/mL (per mL): $40.67Solution Pen-injector (Tresiba FlexTouch Subcutaneous)100 units/mL (per mL): $40.67200 units/mL (per mL): $81.35Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalTregludec (IL);Tresiba (AE, AR, AT, BE, BH, CH, CN, CR, CY, CZ, DE, DK, DO, EE, ES, FI, GB, GR, GT, HK, HN, HR, HU, ID, IE, IN, IS, JP, KR, KW, LB, LT, LU, MT, NI, NL, NO, PA, PH, PL, PT, RO, SE, SI, SK, SV, TH, TR, TW, UA)For country code abbreviations (show table)American College of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi:10.1097/AOG.0000000000002960 [PubMed 30461693]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins - Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]American Diabetes Association (ADA). Standards of medical care in diabetes 2017. Diabetes Care. 2017;40(suppl 1):S1-135.American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.American Diabetes Association (ADA). Standards of medical care in diabetes–2022. Diabetes Care. 2022;45(suppl 1):S1-S255. https://diabetesjournals.org/care/issue/45/Supplement_1. Accessed July 7, 2022.Anderson PO. Treating diabetes during breastfeeding. Breastfeed Med. 2018;13(4):237-239. doi:10.1089/bfm.2018.0036 [PubMed 29608329]Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362. doi:10.1210/jc.2014-3415 [PubMed 25590212]Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617]Bonora BM, Avogaro A, Fadini GP. Exposure to insulin degludec during pregnancy: report of a small series and review of the literature. J Endocrinol Invest. 2019;42(3):345-349. [PubMed 30043095]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Copeland KC, Silverstein J, Moore KR, et al; American Academy of Pediatrics. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382. doi: 10.1542/peds.2012-3494. [PubMed 23359574]Couper JJ, Haller MJ, Ziegler AG, Knip M, Ludvigsson J, Craig ME. Phases of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2014;15(suppl 20):18-25. [PubMed 25325095]Cruijsen M, Koehestani P, Huttjes S, Leenders K, Janssen I, de Boer H. Perioperative glycaemic control in insulin-treated type 2 diabetes patients undergoing gastric bypass surgery. Neth J Med. 2014;72(4):202-209. [PubMed 24829176]Danne T, Bangstad HJ, Deeb L, et al. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes. 2014;15(suppl 20):115-134. [PubMed 25182312]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;61(12):2461-2498. doi:10.1007/s00125-018-4729-5 [PubMed 30288571]DiMeglio LA, Acerini CL, Codner E, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes. 2018;19(suppl 27):105-114. [PubMed 30058221]Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. doi:10.4158/CS-2019-0472 [PubMed 32022600]Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21(suppl 1):1-87. doi:10.4158/EP15672.GL [PubMed 25869408]Hiranput S, Ahmed SH, Macaulay D, Azmi S. Successful outcomes with insulin degludec in pregnancy: a case series. Diabetes Ther. 2019;10(1):283-289. [PubMed 30443804]Jefferies C, Rhodes E, Rachmiel M, et al. ISPAD clinical practice consensus guidelines 2018: management of children and adolescents with diabetes requiring surgery. Pediatr Diabetes. 2018;19(suppl 27):227-236. doi:10.1111/pedi.12733 [PubMed 30039617]Keller MF, Vestgaard M, Damm P, Mathiesen ER, Ringholm L. Treatment with the long-acting insulin analog degludec during pregnancy in women with type 1 diabetes: an observational study of 22 cases. Diabetes Res Clin Pract. 2019;152:58-64. doi:10.1016/j.diabres.2019.05.004 [PubMed 31102682]Khan NA, Ghali WA, Cagliero E. Perioperative management of blood glucose in adults with diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022.Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am. 2012;41(1):57-87. doi:10.1016/j.ecl.2012.03.001 [PubMed 22575407]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists - executive summary. Endocr Pract. 2019;25(12):1346-1359. doi:10.4158/GL-2019-0406 [PubMed 31682518]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Pichardo-Lowden A, Gabbay RA. Management of hyperglycemia during the perioperative period. Curr Diab Rep. 2012;12(1):108-118. doi:10.1007/s11892-011-0239-2 [PubMed 22086363]Reader D, Franz MJ. Lactation, diabetes, and nutrition recommendations. Curr Diab Rep. 2004;4(5):370-376. [PubMed 15461903]Ringholm L, Do NC, Damm P, Mathiesen ER. Pregnancy outcomes in women with type 1 diabetes using insulin degludec. Acta Diabetol. 2022;59(5):721-727. doi:10.1007/s00592-021-01845-0 [PubMed 35147781]Rosenstock J, Cheng A, Ritzel R, et al. More similarities than differences testing insulin glargine 300 units/mL versus insulin degludec 100 Units/mL in insulin-naive type 2 diabetes: the randomized head-to-head BRIGHT trial. Diabetes Care. 2018;41(10):2147-2154. doi:10.2337/dc18-0559 [PubMed 30104294]Tresiba (insulin degludec) [prescribing information]. Plainsboro, NJ: Novo Nordisk; July 2022.Umpierrez GE, Hellman R, Korytkowski MT, et al; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16-38. doi:10.1210/jc.2011-2098 [PubMed 22223765]Vora J, Cariou B, Evans M, et al. Clinical use of insulin degludec. Diabetes Res Clin Pract. 2015;109(1):19-31. [PubMed 25963320]Wexler DJ. Initial management of hyperglycemia in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022a. [PubMed 25963320]Wexler DJ. Insulin therapy in type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022b.Whitmore TJ, Trengove NJ, Graham DF, Hartmann PE. Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:296368. [PubMed 22500167]Zeitler P, Fu J, Tandon N, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2014;15(Suppl 20):26-46. [PubMed 25182306]Topic 104418 Version 156.0

Insulin glargine and lixisenatide: Drug information

CloseInsulin glargine and lixisenatide: Drug informationInsulin glargine and lixisenatide: Drug information(For additional information see "Insulin glargine and lixisenatide: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USSoliquaBrand Names: CanadaSoliquaPharmacologic CategoryAntidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist;Insulin, Long-ActingDosing: AdultDiabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). Consider a dose reduction (eg, by 50%) or discontinuation of insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (AACE/ACE [Garber 2020]; ADA/EASD [Davies 2018]).SUBQ:Initial:Note: Discontinue therapy with basal insulin or a GLP-1 agonist prior to initiation of the combination product.Patients naive to basal insulin or a GLP-1 agonist, or currently on a GLP-1 agonist or <30 units of basal insulin/day: 15 units (insulin glargine 15 units/lixisenatide 5 mcg) once daily.Patients currently on 30 to 60 units of basal insulin/day, with or without a GLP-1 agonist: 30 units (insulin glargine 30 units/lixisenatide 10 mcg) once daily.Dose titration: Titrate the dosage upwards or downwards by 2 to 4 units (insulin glargine 2 to 4 units/lixisenatide 0.66 to 1.32 mcg) every week until the desired fasting plasma glucose is achieved; usual dosage range: 15 units (insulin glargine 15 units/lixisenatide 5 mcg) to 60 units (insulin glargine 60 units/lixisenatide 20 mcg)/day. Maximum dose: 60 units (insulin glargine 60 units/lixisenatide 20 mcg)/day.Missed dose: If a dose is missed, resume with the next scheduled dose. Do not double dose or increase the dose to make up for the missed dose.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdulteGFR ≥15 mL/minute/1.73 m2 to <90 mL/minute/1.73 m2: There are no specific dosage adjustments provided in the manufacturer's labeling for the combination product; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely. Limited data indicates lixisenatide exposure is increased in patients with severe impairment (eGFR <30 mL/minute/1.73 m2). Also refer to individual monographs.eGFR <15 mL/minute/1.73 m2: Use is not recommended (has not been studied).Dosing: Hepatic Impairment: AdultThere are no specific dosage adjustments provided in the manufacturer's labeling for the combination product; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely. Also refer to individual monographs.Dosing: Older AdultRefer to adult dosing; use with cautionDosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Soliqua: 100/33: Insulin glargine 100 units and lixisenatide 33 mcg per mL (3 mL) [contains metacresol]Generic Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Pen-injector, Subcutaneous: Soliqua: 100/33: Insulin glargine 100 units and lixisenatide 33 mcg per mL (3 mL) [contains metacresol]Medication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208673s012lbl.pdf#page=29Administration: AdultSUBQ: For SUBQ use only. Do not administer IM, IV, or via an insulin pump. Cold injections should be avoided. Inject into the abdomen, thigh, or upper arm. Rotate injection sites for each dose; do not use the same site for each injection to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Administer within one hour before the first meal of the day, preferably the same meal each day. Solution should appear clear and colorless; do not use if particulate matter or coloration is seen. Do not split the dose. Do not mix or dilute with any other insulin or solution. Prefilled pen dials in 1-unit increments. For the prefilled pen, prime the needle before each injection with 2 units of medication (use a new needle for each injection). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 10 seconds. Then, remove the needle.Use: Labeled IndicationsDiabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.Medication Safety IssuesHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.Other safety concerns:Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.>10%:Endocrine & metabolic: Hypoglycemia (8% to 18%; severe hypoglycemia: ≤1%)Immunologic: Antibody development (anti-insulin glargine antibodies: 21% to 26%; anti-lixisenatide antibodies: 43%)1% to 10%:Gastrointestinal: Diarrhea (7%), nausea (10%), vomiting (3%)Local: Injection site reaction (2%)Nervous system: Headache (5%)Respiratory: Nasopharyngitis (7%), upper respiratory tract infection (6%)Frequency not defined:Gastrointestinal: Abdominal distention, abdominal pain, constipation, decreased appetite, dyspepsia, flatulence, gastritis, gastroesophageal reflux diseaseLocal: Hypertrophy at injection site, lipoatrophy at injection sitePostmarketing:Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)Gastrointestinal: Cholecystitis, cholelithiasis (requiring cholecystectomy)Hypersensitivity: Anaphylaxis, angioedema, severe hypersensitivity reactionsRenal: Acute kidney injury, exacerbation of renal failureContraindicationsHistory of serious hypersensitivity to insulin glargine, lixisenatide, or any component of the formulation; during episodes of hypoglycemia.Canadian labeling: Additional contraindications (not in US labeling): Patients with a personal or family history of medullary thyroid carcinoma; patients with multiple endocrine neoplasia syndrome type 2; pregnancy; breastfeeding.Warnings/PrecautionsConcerns related to adverse effects:• Antibody formation: Development of antibodies to insulin and lixisenatide may occur; in clinical trials with lixisenatide, high titers were observed in 2.4% of patients and were associated with an attenuated glycemic response. Allergic reactions and injection site reactions were more frequent in antibody positive patients; consider alternative antidiabetic therapy in patients not achieving targeted glycemic control or with worsening glycemic control and/or significant allergic or injection site reactions.• Gallbladder disease: Use of glucagon-like peptide-1 (GLP-1) agonists may increase risk of gallbladder and bile duct disease, including cholelithiasis and cholecystitis (Faillie 2016; Monami 2017; Pfeffer 2015). Cholelithiasis and cholecystitis have been reported with lixisenatide use.• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with lixisenatide and with insulin glargine; discontinue use if hypersensitivity reactions occur and treat promptly as indicated. It is not known if patients with a history of hypersensitivity to other GLP-1 agonists are at increased risk for hypersensitivity reactions with lixisenatide; patients with prior serious reactions to similar agents should be monitored closely.• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine, insulin degludec) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported with GLP-1 receptor agonists; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain which may radiate to the back, and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis (has not been studied).Disease-related concerns:• Bariatric surgery:– Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).– Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. Rates and timing of type 2 diabetes improvement and resolution vary widely by patient; insulin dose reduction of 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014).– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.• Gastroparesis: Lixisenatide slows gastric emptying and is not recommended for use in patients with gastroparesis (has not been studied); do not initiate therapy in patients with severe gastroparesis.• Renal impairment: Use with caution in patients with renal impairment. Dosage adjustments may be necessary. Patients with mild to moderate renal impairment (eGFR ≥30 to 89 mL/minute/1.73 m2) may be at increased risk of adverse effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration, acute kidney injury, and worsening of chronic renal failure. There is limited experience with severe impairment (eGFR 15 to <30 mL/minute/1.73 m2); lixisenatide exposure may be increased in these patients. Monitor all patients with renal impairment closely for decreasing renal function. Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2) (has not been studied).• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage adjustments may be necessary.Dosage form specific issues:• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Appropriate use: Not approved for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationAlpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyAntidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEdetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGlucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHerbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyHormonal Contraceptives: May diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modificationHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyInsulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins.Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationLiraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationMacimorelin: Insulins may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMeglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides.Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modificationMetreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin.Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modificationPramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modificationProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyRosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination.Risk X: Avoid combinationSalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySemaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combinationSincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationSulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas.Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyPregnancy ConsiderationsAdverse events were observed in some animal reproduction studies. Refer to individual monographs for additional information.Breastfeeding ConsiderationsIn a study using insulin glargine, both exogenous and endogenous insulin were present in breast milk (Whitmore 2012).According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Refer to individual monographs for additional information.Dietary ConsiderationsIndividualized medical nutrition therapy based on American Diabetes Association recommendations is an integral part of therapy.Monitoring ParametersDiabetes mellitus: Plasma glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors; some patients may be candidates for continuous glucose monitoring) (ADA 2021); electrolytes; hepatic function; weight; potassium (in patients at risk for hypokalemia); renal function; signs/symptoms of pancreatitis (eg, persistent severe abdominal pain, which may radiate to the back and which may or may not be accompanied by vomiting); signs/symptoms of gallbladder disease; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 2018).Reference RangeRecommendations for glycemic control in patients with diabetes:Nonpregnant adults (ADA 2021):HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).Older adults (≥65 years of age) (ADA 2021):Note: May consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).Pregnant patients:HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2021):Preconception (patients planning for pregnancy): <6.5%.During pregnancy <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2021).Gestational diabetes mellitus (ACOG 2018; ADA 2021):Fasting: <95 mg/dL.Postprandial: <140 mg/dL (at 1 hour) or <120 mg/dL (at 2 hours).Pregestational diabetes mellitus (type 1 or type 2) (ADA 2021):Fasting: 70 to 95 mg/dL.Postprandial: 110 to 140 mg/dL (at 1 hour) or 100 to 120 mg/dL (at 2 hours).Hospitalized adult patients (ADA 2021): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia). Initiate insulin therapy for persistent hyperglycemia at ≥180 mg/dL.Perioperative care in adult patients (ADA 2021): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL.Classification of hypoglycemia (ADA 2021):Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.Mechanism of ActionRefer to individual agents.Pharmaco*kineticsRefer to individual agents.Pricing: USSolution Pen-injector (Soliqua Subcutaneous)100-33UNT-MCG/ML (per mL): $64.64Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalSoliqua (AT, BE, CZ, EE, HK, HR, IL, LT, MY, PH, PT, RO, SG, TH, TW)For country code abbreviations (show table)American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. doi:10.1097/AOG.0000000000002501 [PubMed 29370047]American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care.diabetesjournals.org/content/44/Supplement_1. Accessed January 12, 2021.Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(5):2135-2136]. J Clin Endocrinol Metab. 2015;100(2):342-362. doi:10.1210/jc.2014-3415 [PubMed 25590212]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed December 22, 2016.Cruijsen M, Koehestani P, Huttjes S, Leenders K, Janssen I, de Boer H. Perioperative glycaemic control in insulin-treated type 2 diabetes patients undergoing gastric bypass surgery. Neth J Med. 2014;72(4):202-209. [PubMed 24829176]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]Faillie JL, Yu OH, Yin H, Hillaire-Buys D, Barkun A, Azoulay L. Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus. JAMA Intern Med. 2016;176(10):1474‐1481. doi:10.1001/jamainternmed.2016.1531 [PubMed 27478902]Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. doi:10.4158/CS-2019-0472 [PubMed 32022600]Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115. [PubMed 32998798]Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]Monami M, Nreu B, Scatena A, et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials. Diabetes Obes Metab. 2017;19(9):1233‐1241. doi:10.1111/dom.12926 [PubMed 28244632]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Pfeffer MA, Claggett B, Diaz R, et al; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247‐2257. doi:10.1056/NEJMoa1509225 [PubMed 26630143]Soliqua (insulin glargine/lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; June 2022.Soliqua (insulin glargine/lixisenatide) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; April 2021.Whitmore TJ, Trengove NJ, Graham DF, Hartmann PE. Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:296368. [PubMed 22500167]Topic 110982 Version 118.0