Dosing & Uses
Dosage Forms & Strengths
injectable suspension
- 2mg/vial (Bydureon) - planned discontinuation from U.S. market is September 30, 2018
- 2mg/syringe pen (Bydureon)
injectable suspension, single-dose autoinjector
- 2mg/0.85mL (Bydureon BCise)
Diabetes Mellitus Type 2
Indicated as adjunct to diet and exercise to improve glycemic control with DM type 2
2 mg SC once weekly
Initiating therapy
- Prior treatment with an immediate- or extended-release exenatide product is not required
- Discontinue an immediate- or extended-release exenatide product prior to initiation of Bydureon or Bydureon BCise
- Patients changing from immediate-release exenatide to Bydureon/Bydureon BCise may experience transient (~2-4 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 (eCrCl <30 mL/min) or end-stage renal disease (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
Dosing Considerations
Limitations of use
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
- Should not be used to treat type 1 diabetes or diabetic ketoacidosis
- Concurrent use with prandial insulin has not been studied
- Do not coadminister with other exenatide containing products
- Has not been studied in patients with a history of pancreatitis; consider other antidiabetic therapies in patients with a history of pancreatitis
Safety and efficacy not established
Bydureon
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 BCise
In 2 comparator-controlled 28-week trials, exenatide auto-injector was studied in 74 patients (18%) who were at least 65 years old and 10 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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Injection site nodule, Bydureon BCise (10.5%)
Bydureon
- Nausea (11-24%)
- Diarrhea (11-20%)
- Hypoglycemia (with sulfonylurea) (12.5-20%)
- Vomiting (11.3%)
1-10%
Bydureon
- 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%)
Bydureon BCise
- Nausea (8.2%)
- Headache (4.4%)
- Diarrhea (4%)
- Vomiting (3.4%)
- Injection site pruritus (3.2%)
- Dizziness (2.5%)
- Injection site erythema (2.3%)
- Constipation (2.1%)
Postmarketing Reports
Allergy/hypersensitivity: Injection-site reactions, generalized pruritus and/or urticaria, macular or papular rash, angioedema; anaphylactic reaction
Drug interactions: Increased INR sometimes associated with bleeding, with concomitant warfarin
Gastrointestinal: Nausea, vomiting, and/or diarrhea resulting in dehydration; abdominal distension, abdominal pain, eructation, constipation, flatulence, acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death
Neurologic: Dysgeusia; somnolence
Renal and urinary disorders: Altered renal function (eg, increased serum creatinine, renal impairment, worsened chronic renal failure or acute renal failure [sometimes requiring hemodialysis], kidney transplant and kidney transplant dysfunction)
Skin and subcutaneous tissue disorders: Alopecia
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
- Counsel patients regarding the potential risk of MTC and symptoms (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness) of thyroid tumors
Contraindications
Hypersensitivity to exenatide or to any of the product components
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)
Pancreatitis reported, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis; discontinue promptly if pancreatitis is suspected
Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema); inform and closely monitor patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist for allergic reactions; it is unknown whether such patients will be predisposed to anaphylaxis (see Contraindications)
Antibodies to exenatide following treatment may develop; anti-exenatide antibodies were measured in controlled studies; patients with higher titer antibodies may have an attenuated HbA1c response; if glycemic control worsens, consider alternative antidiabetic therapy
Not recommended with severe gastrointestinal disease (eg, gastroparesis)
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
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction
Acute events of gallbladder disease reported in GLP-1 receptor agonist trials; if cholelithiasis suspected, gallbladder studies and appropriate clinical follow-up indicated
Acute kidney injury and renal impairment
- Renal impairment reported, including some instances requiring hemodialysis and kidney transplantation; not recommended if severe renal impairment or ESRD exist
- Monitor patients with mild renal impairment for adverse reactions that may lead to hypovolemia; drug is not recommended for use in patients with eGFR below 45 mL/min/1.73 m² or end -stage renal disease; if used in patients with renal transplantation, closely monitor for adverse reactions that may lead to hypovolemia
- Caution in patients with renal transplantation or moderate renal impairment
- Not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease; should be used with caution in patients with renal transplantation
- Therapy may induce nausea and vomiting with transient hypovolemia and may worsen renal function; not recommended for use in patients with an eGFR below 45mL/min/1.73 m²
Drug interactions overview
- Use caution when administering oral medications with Bydureon and Bydureon BCise where a slower rate of oral absorption may be clinically meaningful
- Postmarketing reports for exenatide of increased INR with concomitant use of warfarin, sometimes associated with bleeding; monitor INR
- Risk of hypoglycemia is increased when exenatide is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin; lower dose of the secretagogue or insulin to reduce risk of hypoglycemia
Pregnancy & Lactation
Pregnancy
Limited data with exenatide in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage
Based on animal reproduction studies, there may be risks to the fetus from exposure to exenatide injection during pregnancy
Exenatide extended-release injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide extended-release during pregnancy or from exposure to exenatide during pregnancy and lactation, in association with maternal effects
Lactation
There is no information on the presence of exenatide, in human milk, the effects of exenatide on the breastfed infant, or the effects of exenatide on milk production
Exenatide was present in the milk of lactating mice; exenatide concentration in milk was up to 2.5% of the concentration in maternal plasma after administering SC injection twice a day
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
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
Bydureon
- Peak Plasma Time: Gradual increase observed over 6-7 weeks after initiating
- Peak Plasma Concentration: 300 pg/mL (after 6-7 weeks)
Bydureon BCise
- Peak plasma concentration, steady-state: 208 pg/mL
Distribution
Vd: 28.3 L
Elimination
Renal clearance: 9.1 L/hr
Excretion: Predominantly urine
Administration
SC Preparation
Bydureon
- 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
- Final concentration of suspension is 2 mg/0.65 mL
- The suspension should be white to off-white and cloudy
Bydureon BCise
- Remove autoinjector from the refrigerator 15 minutes prior to resuspending the suspension
- Shake vigorously for at least 15 seconds
- Drug should appear as an opaque, white to off-white suspension (autoinjector contains microspheres which appear as white to off-white particles)
- Visually inspect for particulate matter and discoloration prior to administration
- Do not use if foreign particulate matter is present or if discoloration is observed
SC Administration
Subcutaneous use only
Use immediately after autoinjector is prepared or following reconstitution (vial)
Administer as SC injection in abdomen, thigh or upper arm region
Rotate injection sites each week when injecting in the same region
Do not administer IV or IM
Administer with or without meals
Administration with basal insulin
- Always administer exenatide and basal insulin as separate injections; do not mix these medications together into a single injection
- It is acceptable to inject exenatide and basal insulin in the same body region, but the injections should not be adjacent to each other
Missed dose
- Missed dose and next dose is due at least 3 days later: Administer dose as soon as possible; resume usual dosing schedule of qWeek thereafter
- Missed dose and next dose is due 1 or 2 days later: Do not administer missed dose; resume next regularly scheduled dose
Storage
Keep out of reach of children
Unopened vials
- Refrigerate at 36-46°F (2-8°C); do not freeze; do not use if suspension has been frozen
- Protect from light If needed, can be kept at room temperature (not to exceed 77°F [25°C]) for no more than a total of 4 weeks
Reconstituted vials
- Use immediately, do not store
Images
Patient Handout
Formulary
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