Usual Adult Dose for Diabetes Type 2

Immediate-release (Byetta):
Initial dose: 5 mcg subcutaneously twice a day within the 60-minute period before the morning and evening meals

• Maintenance dose: After 1 month, may increase dose to 10 mcg subcutaneously twice a day based on clinical response
• Maximum dose: 10 mcg twice a day
• Alternatively, may give before the two main meals of the day provided dosing is 6 hours or more apart

Extended-release (Bydureon; Bydureon BCISE):
Initial dose: 2 mg subcutaneously once every 7 days (weekly)

• May administer any time of day, with or without meals; see dose adjustments for information on missed doses and changing administration day
• Prior treatment with immediate-release product is not required; for patients who do switch, discontinue immediate-release at initiation of extended-release; transient blood glucose elevations may occur for approximately 2 to 4 weeks after switch
• Switching extended-release products may be done at next regularly scheduled dose

Comments:

• This drug has not been studied in patients with a history of pancreatitis and therefore, other therapies should be considered in these patients.
• Extended-release exenatide is not recommended as first-line therapy because of the uncertainty of the risk of thyroid C-cell tumors.
• Patients may experience transient (approximately 2 to 4 weeks) elevation in blood sugar when switching from immediate-release exenatide to extended-release.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Usual Pediatric Dose for Diabetes Type 2

10 years and older:
Extended-release (Bydureon; Bydureon BCISE): 2 mg subcutaneously once every 7 days (weekly)

• May administer any time of day, with or without meals; see dose adjustments for information on missed doses and changing administration day

Comments:

• Extended-release exenatide is not recommended as first-line therapy because of the uncertainty of the risk of thyroid C-cell tumors.
• This drug is not indicated for use in patients with type 1 diabetes.
• This drug has not been studied in patients with a history of pancreatitis and therefore, other therapies should be considered in these patients.

Use: As an adjunct to diet and exercise to improve glycemic control in pediatric patients 10 years and older with type 2 diabetes mellitus.

Renal Dose Adjustments

Immediate-release (Byetta):

• Mild renal impairment (CrCl 50 to 80 mL/min): No adjustment recommended
• Moderate renal impairment (CrCl 30 to 50 mL/min): Use with caution, especially when escalating dose
• ESRD or severe renal impairment (CrCl less than 30 mL/min): Not recommended

Extended-release (Bydureon; Bydureon BCISE):

• eGFR 45 mL/min/1.73 m2 or greater: No adjustment recommended
• eGFR less than 45 mL/min/1.73 m2: Not recommended
• ESRD: Not recommended

Renal transplantation: Use with caution; closely monitor for adverse reactions that may lead to hypovolemia

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Elderly: Use caution when initiating therapy as elderly patients are more likely to have decreased renal function.

Concomitant use with Insulin or Insulin Secretagogues (e.g. sulfonylureas)

• Patients receiving an insulin or insulin secretagogues in combination with exenatide may require a lower dose of the insulin or insulin secretagogue to reduce the risk of hypoglycemia.

Missed doses:
Immediate-release:

• If a dose is missed, resume therapy with next scheduled dose

Extended-release:

• If a dose is missed and the next regularly scheduled dose is due at least 3 days later, administer missed dose and resume usual dosing schedule
• If a dose is missed and the next regularly scheduled dose is due in 1 or 2 days, skip the missed dose and resume usual dosing schedule
• Do not take 2 doses within 3 days of each other

Changing Administration Day:

• The day of weekly administration can be changed as long as the last dose was administered 3 or more days before the new day of administration.

Precautions

US BOXED WARNINGS: RISK OF THYROID C-CELL TUMORS (extended-release formulations)

• Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether this drug causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide-extended-release-induced rodent thyroid C-cell tumors has not been determined.
• The extended-release formulation is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Patients should be counseled regarding the potential risk for MTC and inform them of the symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring for serum calcitonin or using thyroid ultrasounds is of uncertain value for detection of MTC in patients treated with exenatide extended-release.

CONTRAINDICATIONS:

• Severe hypersensitivity reactions to the active substance or any product ingredients
• A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (extended-release formulations)
• History of drug-induced-immune-mediated thrombocytopenia from exenatide products; serious bleeding, including fatalities has been reported

Safety and efficacy have not been established in patients younger than 18 years (immediate-release).
Safety and efficacy have not been established in patients younger than 10 years (extended-release).

Consult WARNINGS section for additional precautions.

Dialysis

Not recommended in patients with ESRD

Other Comments

Administration advice:

• Administer subcutaneously in abdomen, thigh, or upper arm region; rotate injection sites
• Do not administer IV or IM
• Never share a pen between patients, even if the needle is changed, due to risk for transmission of blood-borne pathogens

IMMEDIATE-RELEASE (Byetta):

• Administer subcutaneously twice a day within 60-minutes of the morning and evening meal
• Alternatively, may give within 60-minutes before the two main meals of the day provided dosing is 6 hours or more apart
• Do not administer after a meal; if a dose is missed, resume with next scheduled dose

EXTENDED-RELEASE (Bydureon; Bydureon BCISE):

• Administer subcutaneously once every 7 days (weekly) at any time of the day, with or without meals
• If a dose is missed, administer as soon as noticed provided the next regularly scheduled dose is at least 3 days later; then resume usual dosing schedule
• If a dose is missed and the next regularly scheduled dose is 1 or 2 days later, skip missed dose and resume with the next regularly scheduled dose.
• The day of weekly administration can be changed as long as the last dose administered was 3 or more days before the new day of administration; do not take 2 extended-release doses within 3 days of each other.

Storage requirements: Protect from light; do not freeze (discard if frozen)

• Immediate-release Pens (Byetta): Unopened (not in use): Store in refrigerator 2C to 8C (36F to 46F); Opened (in-use): Store below 25C (77F); may be refrigerated; discard 30 days after opening
• Extended-release Pens and Trays (Bydureon): Unopened (not in use): Store in refrigerator 2C to 8C (36F to 46F); may be stored at room temperature (below 25C [77F]) for no more than a total of 4 weeks, if needed; Once suspension is prepared: Use immediately
• Extended-release Auto-injector (Bydureon BCISE): Unopened (not in use): Store flat in refrigerator 2C to 8C (36F to 46F); may be stored at room temperature (below 30C [86F]) for no more than a total of 4 weeks, if needed; Once suspension is prepared: Use immediately

Reconstitution/Preparation Techniques:

• Patients should receive proper training from their healthcare provider prior to first use.
• Do not substitute needles or any other components provided for administration.
• Product labeling should be consulted for specific instructions.

General:

• This drug has not been studied in patients with a history of pancreatitis, alternative therapy should be considered in these patients.
• This drug should not be used to treat patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; this drug is not a substitute for insulin.
• The extended-release formulation of this drug is not recommended as a first-line therapy in patients with type 2 diabetes mellitus as the relevance of rat thyroid C-cell tumor findings to humans is uncertain.
• For patients switching from immediate-release to extended-release exenatide, blood glucose concentrations may be elevated for the first 2 to 4 weeks after the switch.

Monitoring:

• Blood glucose and hemoglobin A1C measurements should be measured periodically to assess efficacy
• Observe for signs and symptoms of pancreatitis, acute gallbladder disease
• Observe for signs and symptoms of thyroid tumors
• Observe injection sites for signs or symptoms of abscess, cellulitis, or necrosis

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Patients should be advised to never share a pen with another person, even if the needle is changed; patients should understand that sharing needles or syringes with another person carries a risk for transmission of blood-borne pathogens.
• Counsel patients to report symptoms of thyroid tumors such as a lump in their neck, persistent hoarseness, dysphagia, or dyspnea.
• Patients should be aware that they may experience a reduction in appetite, food intake, and/or weight loss; nausea may occur early in therapy and generally resolves; if excess weight loss occurs, they should consult a healthcare provider.
• Patients should be instructed to promptly seek medical advice for signs and symptoms of pancreatitis, acute gallbladder disease, and/or symptoms of thrombocytopenia (e.g., unusual bruising or bleeding).
• Patients should be instructed to seek medical advice during periods of stress, such as fever, trauma, infection, or surgery as medical management of diabetes may change.
• Inform patients that hypersensitivity reactions may occur; for a serious or severe reaction, patient should seek immediate medical attention.
• Patients should be aware of signs and symptoms of hypoglycemia and how it should be managed; patients should understand that the risk of hypoglycemia is increased if used in combination with a sulfonylurea or insulin.
• Patients should be advised to take precautions to avoid hypoglycemia while performing hazardous tasks including driving.

Frequently asked questions

• How long does it take for Bydureon Bcise to take effect?
• How long can Bydureon be unrefrigerated?
• How does Bydureon work?
• How do you use the Bydureon pen?
• How do you use the Bydureon Bcise autoinjector?