Dosing and uses of Byetta (exenatide)
Adult dosage forms and strengths
injectable solution, prefilled pen
- 250mcg/mL (1.2mL vial)
- 250mcg/mL (2.4mL vial)
Diabetes Mellitus, Type 2
Adjunct to diet and exercise to improve glycemic control with DM type 2; monotherapy or as an adjunct therapy with thiazolidinediones, metformin, or a sulfonylurea; or add-on therapy to insulin glargine (a long-acting insulin), with or without metformin and/or a thiazolidinedione, in patients who are not achieving adequate glycemic control on insulin glargine alone
Immediate-release (Byetta): 5 mcg SC q12hr within 60 minutes prior to meal intially; after 1 month, may increased to 10 mcg q12hr
Switching from immediate-release to extended-release
- Initiate weekly extended-release SC injections 1 day after discontinuing immediate-release exenatide (Byetta)
- May experience increased blood glucose levels for approximately 2 weeks after initiating extended-release (Bydureon) therapy
- May initiate extended-release exenatide without pretreating with the immediate-release dosage form
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
Pediatric dosage forms and strengths
Safety and efficacy not established
Byetta (exenatide) adverse (side) effects
>10%
Injection-site nodule (6-77%)
Injection-site reactions (2-18%)
Nausea (8-11%)
Vomiting (4-11%)
Diarrhea (2-11%)
1-10%
Constipation (6-10%)
Headache (5-9%)
Dyspepsia (3-7%)
Hyperhidrosis (3%)
Jitteriness (<3%)
Dizziness (<2%)
Asthenia
Postmarketing Reports
Alopecia
Anaphylactic reaction
Angioedema
Pancreatitis
Rash
Renal impairment
Upper respiratory infection
Warnings
Black box warnings
Risk of thyroid C-cell tumors
- 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
ESRD, severe renal impairment (CrCl <30 mL/min)
Family or current history of medullary thyroid carcinoma
Cautions
Never share a pen between patients even if the needle is changed
Not a substitute for insulin
Not a first-line therapy for patients inadequately controlled on diet and exercise alone
Evaluate insulin dose when added on to long-acting insulin (ie, insulin glargine); in patients with increased risk of hypoglycemia, consider decreasing insulin dose
Not recommended for patients experiencing severe gastrointestinal disease, including gastroparesis
Not recommended for type 1 diabetes
Do not take with short- and/or rapid-acting insulins
Animal studies show association of extended-release dosage form with the formation of thyroid tumors (effects in humans unknown)
Always administer before a meal and never after a meaL
Weight loss resulting from reduced intake reported
Risk of acute pancreatitis reported, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis
Increased risk of hypoglycemia in patients taking insulin secretagogues; may require dose reduction of sulfonylureas
Risk of renal failure
Antibody formation to exenatide is likely; up to 4% of patients may have worsening glycemic control and require alternative antidiabetic therapy
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in milk unknown; use with caution
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 Byetta (exenatide)
Mechanism of action
A glucagonlike peptide-1 (GLP-1) that mimics incretin and promotes insulin secretion, suppresses glucagon, and slows gastric emptying
Absorption
Peak plasma time: 2.1 hr
Peak plasma concentration: 211 pg/mL
AUC: 1036 pg·hr/mL
Distribution
Vd: 28.3 L
Metabolism
Proteolytic degradation following glomerular filtration
Elimination
Half-life: 2.4 hr (immediate release); 2 weeks (extended release)
Renal clearance: 9.1 L/hr
Excretion: Urine (primarily)
Administration
SC Administration
Administer within 60 minutes before morning and evening meals, approximately 6 hr or more apart
Administer SC only; do not administer IM or IV
Injection sites are thigh, abdomen, or upper arm
