Dosing and uses of Bydureon (exenatide injectable suspension)
Adult dosage forms and strengths
injectable suspension
- 2mg/vial
- 2mg/syringe pen
Diabetes Mellitus Type 2
Indicated as adjunct to diet and exercise to improve glycemic control with DM type 2; not recommended as first-line therapy if inadequately controlled on diet and exercise; use with insulin has not been studied and is not recommended
2 mg SC once weekly
Changing from Byetta to Bydureon
- Prior treatment with Byetta (short-acting exenatide) is not required when initiating Bydureon therapy
- If starting Bydureon in a patient already taking Byetta, discontinue Byetta
- Patients may experience transient (~2 weeks) elevations in blood glucose concentrations
Dosage modifications
Renal impairment
- Mild (CrCl 50-80 mL/min): No dosage adjustment required
- Moderate (CrCl 30-50 mL/min): Caution when initiating or escalating dose
- Severe (CrCl <30 mL/min) or ESRD: Not recommended
- Renal transplantation: Use with caution
Hepatic impairment
- Has not been studied; cleared primarily by the kidney; hepatic impairment is not expected to affect blood concentrations
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
In the 5 comparator-controlled trials exenatide injectable suspension was studied in 132 patients (16.6%) who were at least 65 years old and 20 patients who were at least 75 years old
No differences in safety or efficacy were observed between these patients and younger patients
Because elderly patients are more likely to have decreased renal function, use caution
Bydureon (exenatide injectable suspension) adverse (side) effects
>10%
Nausea (11-24%)
Diarrhea (11-20%)
Hypoglycemia (with sulfonylurea) (12.5-20%)
Vomiting (11.3%)
1-10%
Headache (9.4%)
Constipation (8.5%)
Headache (8.1%)
Dyspepsia (7.3%)
Constipation (6.3%)
Fatigue (5.6%)
Dyspepsia (5%)
Decreased appetite (5%)
Injection site pruritus (5%)
Hypoglycemia (without sulfonylurea) (1.3-3.7%)
Postmarketing Reports
Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis
Allergy and hypersensitivity: Injection-site reactions
Warnings
Black box warnings
Risk of thyroid C-cell tumors
- Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls; unknown whether this risk for medullary thyroid carcinoma (MTC) exists in humans, as human relevance could not be determined by clinical or nonclinical studies
- Contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)
- Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with exenatide injectable suspension
- Patients should be counseled regarding the risk and symptoms of thyroid tumors
Contraindications
Hypersensitivity
Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2 (see Black box warnings)
Cautions
Do not administer Byetta and Bydureon concomitantly
Serious injection-site reactions (eg, abscess, cellulitis, and necrosis) reported, with or without SC nodules; some required surgical intervention
Thyroid C-cell tumors in animals observed; human relevance unknown (see Black box warnings); routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with exenatide injectable suspension; significantly elevated serum calcitonin may indicate MTC; patients with MTC usually have values >50 ng/L; if serum calcitonin is measured and found to be elevated, evaluate patient further; patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated
Pancreatitis reported, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis; discontinue promptly if pancreatitis is suspected
Increased risk of hypoglycemia when used in combination with a sulfonylurea or insulin; consider reducing sulfonylurea or insulin dose
Renal impairment reported, including some instances requiring hemodialysis and kidney transplantation; not recommended if severe renal impairment or end-stage renal disease exist
Caution in patients with renal transplantation or moderate renal impairment
Not recommended with severe gastrointestinal disease (eg, gastroparesis)
Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema)
Because exenatide slows gastric emptying, and therefore may reduce absorption rate of some orally administered drugs
Evaluate patient further If serum calcitonin is measured and found to be elevated
Evaluate further patients with thyroid nodules noted on physical examination or neck imaging
Pregnancy and lactation
Pregnancy category: C; Based on animal data, may cause fetal harm; use during pregnancy only if the potential benefit justifies the potential risk to the fetus
Lactation: Unknown whether distributed in human breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Bydureon (exenatide injectable suspension)
Mechanism of action
Glucagon-like peptide-1 (GLP-1) agonist
Incretins, such as GLP-1, enhance glucose-dependent insulin secretion by pancreatic beta-cells, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying
Absorption
Peak Plasma Time: Gradual increase observed over 6-7 weeks after initiating
Peak Plasma Concentration: 300 pg/mL (after 6-7 weeks)
Distribution
Vd: 28/3 L
Elimination
Renal clearance: 9.1 L/hr
Excretion: predominantly urine
Administration
SC Preparation
Examine diluent provided to be sure that it is clear and free of particulate matter
Suspend powder in vial with diluent provided and transfer to syringe
The suspension should be white to off-white and cloudy
SC Administration
Use immediately following reconstitution
Administer as SC injection in abdomen, thigh or upper arm region
Rotate injection site each week
Storage
Unopened vials should be stored in the refrigerator at 36-46°F (2-8°C) and protected from light
Do not freeze; do not use Bydureon if it has been frozen
If needed, each single-dose tray can be kept at room temperature (not to exceed 77°F [25°C]) for no more than a total of 4 weeks
Reconstituted vial: Use immediately, do not store
