exenatide injectable suspension (Rx)

>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

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

Avoid concurrent use of extended release (Bydureon) and immediate release xenatide (Byetta) formulations

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; do not resume therapy unless alternative etiology of pancreatitis is confirmed; consider alternative antidiabetic therapy in patients with history of pancreatitis

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

Pen shaped injection devices should not be used by more than one person, even if needle is changed as it increases risk of infection

Not for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis

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

• Renal impairment reported, including some instances requiring hemodialysis and kidney transplantation; not recommended if severe renal impairment or ESRD exist
• 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; inform patients using these concomitant medications of risk of hypoglycemia and educate them on signs and symptoms of hypoglycemia

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

Use exenatide injection 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.

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

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
• 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

SC 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 or autoinjectors

• 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