(ex EN a tide)
- AC 2993
- Bydureon Bcise
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Bydureon BCise: 2 mg/0.85 mL (0.85 mL)
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)
Brand Names: U.S.
- Bydureon BCise
- Byetta 10 MCG Pen
- Byetta 5 MCG Pen
- Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist
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).
Vd: 28.3 L
Minimal systemic metabolism; proteolytic degradation may occur following glomerular filtration
Urine (majority of dose)
Time to Peak
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).
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 similar to that of patients with healthy renal function. Exposure to immediate-release exenatide increased by 3.37-fold in patients with ESRD receiving dialysis. Exenatide ER has not been studied in patients with severe renal impairment or ESRD receiving dialysis. Population pharmacokinetic analysis of renally impaired patients receiving exenatide 2 mg ER formulation indicated there is a ~28% to 69% increase in exposure in mild and moderate renal impairment, respectively.
Use: Labeled Indications
Diabetes mellitus, type 2: Treatment of type 2 diabetes mellitus to improve glycemic control as an adjunct to diet and exercise.
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
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 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 weeks after conversion. Pretreatment with immediate-release exenatide is not required when initiating extended-release exenatide.
Refer to adult dosing.
Dosing: Renal Impairment
Mild impairment (CrCl >50 mL/minute): No dosage adjustment necessary.
Moderate impairment (CrCl 30 to 50 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling; use caution, particularly with initiation of therapy or dose escalation of immediate release exenatide.
Severe impairment (CrCl <30 mL/minute): Use is not recommended.
End-stage renal disease (ESRD): Use is not recommended.
Dosing: Hepatic Impairment
There 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 pharmacokinetics.
Bydureon: Reconstitute vial/pen using provided diluent; use immediately.
SubQ: Administer via SubQ injection in the upper arm, thigh, or abdomen; rotate injection sites.
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 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.
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.
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
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
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
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. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. 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
Combination therapy may include a sulfonylurea, a thiazolidinedione, insulin glargine, or a combination of oral agents unless otherwise specified. * Frequency not defined.
Central nervous system: Headache (8% to 14%)
Endocrine & metabolic: Hypoglycemia (combination therapy with a sulfonylurea: Byetta 14% to 36%, Bydureon 20%; combination therapy without a sulfonylurea ≤11%; monotherapy ≤5%; Bydureon with metformin 1% to 4%)
Gastrointestinal: Nausea (dose-dependent and usually decreases over time; Byetta combination therapy 40% to 44%, Bydureon combination therapy 9% to 24%, monotherapy 8% to 11%), diarrhea (combination therapy 6% to 20%, Bydureon monotherapy 11%, Byetta monotherapy 1% to <2%), vomiting (combination therapy 11% to 18%, Byetta monotherapy 4%)
Local: Injection site nodule (Bydureon 6% to 77%), injection site reaction (13% to 17%)
1% to 10%:
Cardiovascular: Increased heart rate* (Robinson 2013)
Central nervous system: Dizziness (Byetta combination therapy 9%, Byetta monotherapy 1% to <2%), fatigue (Bydureon combination therapy 6%), jitteriness (Byetta combination therapy 9%)
Dermatologic: Hyperhidrosis (Byetta combination therapy 3%)
Gastrointestinal: Constipation (6% to 10%), viral gastroenteritis (6% to 9%), dyspepsia (3% to 7%), decreased appetite (1% to 5%), abdominal distension (Byetta combination therapy 4%), gastroesophageal reflux disease (Byetta combination therapy 2% to 3%), flatulence (Byetta 2%)
Immunologic: Antibody development to exenatide (2% to 6%, associated with attenuated glycemic response)
Local: Itching at injection site (Bydureon ≥5%)
Neuromuscular & skeletal: Weakness (Byetta combination therapy 4% to 5%)
<1%, postmarketing, and/or case reports (all products): Abscess at injection site, acute pancreatitis, acute renal failure, alopecia, anaphylaxis, angioedema, cellulitis at injection site, chest pain (Byetta combination therapy), chills (Byetta combination therapy), drowsiness, dysgeusia, eructation, hemorrhagic pancreatitis, hypersensitivity pneumonitis (chronic; Byetta combination therapy), increased serum creatinine, influenza, kidney transplant dysfunction, macular eruption, nasopharyngitis, necrotizing pancreatitis (sometimes resulting in death), pain (stomach, side, or abdominal pain possibly radiating to the back), papular rash, prolongation P-R Interval on ECG (Linnebjerg 2011), pruritus, renal function abnormality, renal insufficiency, severe diarrhea, severe hypoglycemia (Byetta combination therapy with metformin and a sulfonylurea), severe nausea, severe vomiting, tissue necrosis at injection site, upper respiratory tract infection, urticaria
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: Use of GLP-1 agonists may increase risk of gallbladder and bile duct disease (Faillie 2016).
• 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.
• 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.
• 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 not recommended in severe renal impairment (CrCl <30 mL/minute) or end-stage renal disease (ESRD). Patients with ESRD receiving dialysis may be more susceptible to GI effects (eg, nausea, vomiting), which may result in hypovolemia and further reductions in renal function. Use with caution in patients with renal transplantation or in patients with moderate renal impairment (CrCl 30 to 50 mL/minute), particularly when initiating or escalating doses with immediate-release exenatide. Cases of acute renal failure and chronic renal failure exacerbation, including severe cases requiring hemodialysis, have been reported, predominately in patients with nausea/vomiting/diarrhea or dehydration; 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.
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).
• 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.
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 2018a]), renal function, weight, triglycerides, signs/symptoms of pancreatitis, signs/symptoms of gallbladder disease (Faillie 2016)
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Based on in vitro data, exenatide has a low potential to cross the placenta (Hiles 2003).
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2018c; Kitzmiller 2008; Metzger 2007). 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 (ACOG 2013; ADA 2018c; Blumer 2013; Kitzmiller 2008). Agents other than exenatide are currently recommended to treat diabetes in pregnant women (ACOG 2013; ADA 2018c; Blumer 2013).
Health care providers are encouraged to enroll women exposed to exenatide during pregnancy in the pregnancy registry (800-633-9081).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience constipation, diarrhea, nausea, vomiting, injection site itching, or loss of strength and energy. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of thyroid cancer (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), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), dizziness, passing out, severe headache, or severe injection site pain, hardness, blisters, lumps, or irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about exenatide
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- Support Group
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- Drug class: incretin mimetics