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Exenatide

Medically reviewed by Drugs.com. Last updated on Jul 7, 2019.

Pronunciation

(ex EN a tide)

Index Terms

  • AC 2993
  • AC002993
  • Exendin-4
  • LY2148568

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Auto-injector, Subcutaneous:

Bydureon BCise: 2 mg/0.85 mL (0.85 mL)

Pen-injector, Subcutaneous [preservative free]:

Bydureon: 2 mg (1 ea)

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])

Brand Names: U.S.

  • Bydureon
  • Bydureon BCise
  • Byetta 10 MCG Pen
  • Byetta 5 MCG Pen

Pharmacologic Category

  • Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

Pharmacology

Exenatide 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).

Distribution

Vd: 28.3 L

Metabolism

Minimal systemic metabolism; proteolytic degradation may occur following glomerular filtration

Excretion

Urine (majority of dose)

Time to Peak

SubQ:

Immediate release (daily) formulation: 2.1 hours

Extended 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).

Half-Life Elimination

Immediate release (daily) formulation: 2.4 hours

Extended release (weekly) formulation: ~2 weeks

Special Populations: Renal Function Impairment

In patients with mild to moderate renal impairment, exposure to exenatide was increased compared with patients with normal renal function.

Use: Labeled Indications

Diabetes mellitus, type 2: Treatment of type 2 diabetes mellitus to improve glycemic control as an adjunct to diet and exercise.

Contraindications

Prior 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)

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; end-stage renal disease (ESRD) or severe renal impairment (CrCl <30 mL/minute) including dialysis patients

Dosing: Adult

Diabetes mellitus, type 2: SubQ:

Immediate release: Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the two main meals of the day, ≥6 hours apart); after 1 month, may be increased to 10 mcg twice daily (based on response).

Missed dose: If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.

Extended release: 2 mg once weekly at any time of day, with or without meals

Missed dose: May administer a missed dose as soon as noticed if the next regularly scheduled dose is due in ≥3 days; resume normal schedule thereafter. If a dose is missed and the next regularly scheduled dose is due 1 or 2 days later, do not administer the missed dose and instead resume treatment with the next regularly scheduled dose. To establish a new day of the week administration schedule, wait ≥3 days after last dose given, then administer next dose on new desired day of the week.

Conversion from immediate release to ER: Initiate weekly administration of exenatide ER the day after discontinuing exenatide immediate release. Note: May experience increased blood glucose levels for ~2 to 4 weeks after conversion. Pretreatment with immediate-release exenatide is not required when initiating ER exenatide.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Bydureon: Reconstitute vial/pen using provided diluent; use immediately.

Administration

SubQ: 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.

ER: May administer without regard to meals or time of day.

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.

Storage

Bydureon 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.

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Estrogen Derivatives (Contraceptive): Exenatide may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulins: 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. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Progestins (Oral Contraceptive): Exenatide may decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sincalide: 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. Consider therapy modification

Sulfonylureas: 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. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Exenatide may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

Incidence rates are for the extended release formulation unless otherwise noted.

>10%:

Gastrointestinal: Nausea (extended release: 8% to 11%; immediate release: 8%), diarrhea (extended release: 4% to 11%; immediate release: ≥1% to 2%)

Immunologic: Immunogenicity (20%, injection site reaction)

Local: Injection site reaction (17%), injection site nodule (11%)

1% to 10%:

Central nervous system: Headache (4% to 8%), dizziness (extended release: 3%; immediate release: ≥1% to 2%)

Dermatologic: Injection site pruritus (3%)

Endocrine & metabolic: Hypoglycemia (4% to 5%), severe hypoglycemia (≤2%)

Gastrointestinal: Constipation (2% to 9%), dyspepsia (extended release: 7%; immediate release: 3%), vomiting (immediate release: 4%, extended release: 3%), decreased appetite (immediate release: ≥1% to <2%)

Immunologic: Antibody development (extended release: 6%; immediate release: 1%; associated with glycemic response)

Local: Erythema at injection site (2% to 5%)

Frequency not defined: Cardiovascular: Increased heart rate (Robinson 2013)

<1%, postmarketing, and/or case reports (all formulations): Abdominal distention, abdominal pain, abscess at injection site, acute pancreatitis, acute renal failure, alopecia, anaphylaxis, angioedema, cellulitis at injection site, drowsiness, dysgeusia, eructation, exacerbation of renal failure, flatulence, hemorrhagic pancreatitis, hypersensitivity reaction, increased serum creatinine, kidney transplant dysfunction, macular eruption, necrotizing pancreatitis, papular rash, prolongation P-R Interval on ECG (Linnebjerg 2011), pruritus, renal function abnormality, renal insufficiency, tissue necrosis at injection site, urticaria

ALERT: U.S. Boxed Warning

Risk 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.

Warnings/Precautions

Concerns related to adverse effects:

• Anti-exenatide antibodies: Use may be associated with the development of anti-exenatide antibodies. Low titers are not associated with a loss of efficacy; however, high titers (observed in 6% to 12% of patients in clinical studies) may result in an attenuation of response.

• 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.

• 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 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 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 patients, monitor for hypovolemia.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

Serum glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]), renal function, volume status, weight, triglycerides, signs/symptoms of pancreatitis, signs/symptoms of gallbladder disease

Pregnancy Considerations

Based 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 birth defects, 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 2019; Blumer 2013).

Agents other than exenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2019).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

• Constipation

• Diarrhea

• Nausea

• Vomiting

• Heartburn

• Injection site itching

• Loss of strength and energy

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like urinary retention, hematuria, change in amount of urine passed, or weight gain.

• Thyroid cancer like new lump or swelling in the neck, pain in the front of the neck, persistent cough, persistent change in voice like hoarseness, or difficulty swallowing or breathing.

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating.

• Dizziness

• Passing out

• Severe headache

• Severe injection site pain, hardness, blisters, lumps, or irritation

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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