A Risk Evaluation and Mitigation Strategy (REMS) is required by the Food and Drug Administration (FDA) to manage known or potential serious risks associated with a drug, and to help ensure that the benefits of the drug outweigh its risks.
To ensure that BYDUREON is prescribed and taken safely, Amylin has developed materials to inform patients and healthcare providers about the risk of acute pancreatitis and the potential risk of medullary thyroid carcinoma associated with the use of BYDUREON. To learn more about these serious risks, read the Medication Guide provided in the links below, including the Important Safety Information .
The goals of the BYDUREON REMS are:
- To inform providers about the risk of acute pancreatitis (including necrotizing and hemorrhagic pancreatitis) and the potential risk of medullary thyroid carcinoma associated with BYDUREON.
- To educate patients about the serious risks associated with BYDUREON.
To learn more, download these important documents:
- REMS for BYDUREON
- Dear Healthcare Professional Letter
- Full Prescribing Information
- Medication Guide
- Highlighted Information for Prescribers
- MTC Registry Information
Important Safety Information for BYDUREON (exenatide extended-release for injectable suspension)
WARNING: 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. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies. BYDUREON is 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 BYDUREON. Patients should be counseled regarding the risk and symptoms of thyroid tumors.
- Patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Patients with prior serious hypersensitivity reactions to exenatide or to any of the product components.
Warnings and Precautions
- Pancreatitis: Based on postmarketing data, exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation of BYDUREON, observe patients carefully for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYDUREON should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
- Hypoglycemia: Increased risk of hypoglycemia when used in combination with a sulfonylurea (SU). Clinicians may consider reducing the SU dose to minimize risk of hypoglycemia. It is possible that use of BYDUREON with other glucose-independent insulin secretagogues (eg, meglitinides) could increase the risk of hypoglycemia.
- Renal Impairment: Should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or moderate renal failure. Postmarketing reports of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation.
- Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYDUREON is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
- Immunogenicity: Patients may develop antibodies to exenatide. In 5 registration trials, attenuated glycemic response was associated in 6% of BYDUREON-treated patients with antibody formation. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
- Hypersensitivity: Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and other suspect medications and promptly seek medical advice.
- Injection-Site Reactions: Postmarketing reports of serious injection-site reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, with the use of BYDUREON.
- Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYDUREON or any other antidiabetic drug.
- In 5 comparator-controlled, 24- to 30-week BYDUREON trials, the incidence of withdrawal due to adverse events was 4.9% for BYDUREON, 4.9% for BYETTA, and 2.0% for other comparators. The most common adverse reactions leading to withdrawal for BYDUREON, BYETTA, and comparators respectively were nausea (0.5%, 1.5%, 0.3%), injection-site nodule (0.5%, 0.0%, 0.0%), diarrhea (0.3%, 0.4%, 0.3%), injection-site reaction (0.2%, 0.0%, 0.0%), and headache (0.2%, 0.0%, 0.0%). One percent of BYDUREON patients withdrew due to injection-site adverse reactions.
Most Common Adverse Reactions (≥5%)
- BYDUREON vs BYETTA:
- 24-week trial: nausea (14% vs 35%), diarrhea (9.3% vs 4.1%), injection-site erythema (5.4% vs 2.4%).
- 30-week trial: nausea (27% vs 33.8%), diarrhea (16.2% vs 12.4%), vomiting (10.8% vs 18.6%), injection-site pruritus (18.2% vs 1.4%), constipation (10.1% vs 6.2%), gastroenteritis viral (8.8% vs 5.5%), gastroesophageal reflux disease (7.4% vs 4.1%), dyspepsia (7.4% vs 2.1%), injection-site erythema (7.4% vs 0.0%), fatigue (6.1% vs 3.4%), headache (6.1% vs 4.8%), injection-site hematoma (5.4% vs 11.0%).
- BYDUREON vs titrated insulin glargine: nausea (12.9% vs 1.3%), headache (9.9% vs 7.6%), diarrhea (9.4% vs 4.0%), injection-site nodule (6.0% vs 0.0%).
- Combination trial vs sitagliptin and pioglitazone: nausea (24.4% vs 9.6% and 4.8%), diarrhea (20.0% vs 9.6% and 7.3%), vomiting (11.3% vs 2.4% and 3.0%), headache (9.4% vs 9.0% and 5.5%), constipation (6.3% vs 3.6% and 1.2%), fatigue (5.6% vs 0.6% and 3.0%), dyspepsia (5.0% vs 3.6% and 2.4%), decreased appetite (5.0% vs 1.2% and 0.0%), injection-site pruritus (5.0% vs 4.8% and 1.2%).
- Monotherapy trial vs sitagliptin, pioglitazone, and metformin: nausea (11.3% vs 3.7%, 4.3%, and 6.9%), diarrhea (10.9% vs 5.5%, 3.7%, and 12.6%), injection-site nodule (10.5% vs 6.7%, 3.7%, and 10.2%), constipation (8.5% vs 2.5%, 1.8%, and 3.3%), headache (8.1% vs 9.2%, 8.0%, and 12.2%), dyspepsia (7.3% vs 1.8%, 4.9%, and 3.3%).
- Hypoglycemia: No major hypoglycemia was reported for BYDUREON- or comparator-treated patients in five 24- to 30-week trials. Minor hypoglycemia incidences for BYDUREON vs comparator-treated patients were as follows: 24-week trial vs BYETTA: with SU, 12.5% vs 11.8%; without SU, 0.0% for both; 30-week trial vs BYETTA: with SU, 14.5% vs 15.4%; without SU, 0.0% vs 1.1%; monotherapy trial vs sitagliptin, pioglitazone, and metformin: 2.0% vs 0.0% (all comparators); combination trial vs sitagliptin and pioglitazone: 1.3% vs 3.0% and 1.2%; vs titrated insulin glargine, with SU, 20.0% vs 43.9%; without SU, 3.7% vs 19.1%.
- Injection-site reactions were observed more frequently in BYDUREON-treated patients (17.1%) vs patients treated with BYETTA (12.7%), titrated insulin glargine (1.8%), or placebo injection (6.4%-13.0%). Injection-site reactions were observed in 14.2% of antibody-positive patients vs 3.1% of antibody-negative patients, with higher incidence in those with higher-titer antibodies. BYETTA-treated patients had similar incidence between antibody-positive and antibody-negative patients (5.8% vs 7.0%). Subcutaneous injection-site nodules may occur with the use of BYDUREON.
- Oral Medications: BYDUREON slows gastric emptying and can reduce the rate of absorption of orally administered drugs. Use with caution with oral medications.
- Warfarin: Postmarketing reports with exenatide of increased international normalized ratio (INR) sometimes associated with bleeding with concomitant use of warfarin. Monitor INR frequently until stable upon initiation or alteration of BYDUREON.
Use in Specific Populations
- Pregnant and Nursing Women: Based on animal data, BYDUREON may cause fetal harm and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To report drug exposure during pregnancy call 1-800-633-9081. When administered to a nursing woman, a decision should be made whether to discontinue nursing or to discontinue BYDUREON.
- Pediatric Patients: Use in pediatric patients is not recommended as safety and effectiveness have not been established.
Indication and Important Limitations of Use for BYDUREON
BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans, prescribe only to patients for whom potential benefits are considered to outweigh potential risk.
- Not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise
- Not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis, and cannot be recommended for use with insulin.
- BYDUREON and BYETTA® (exenatide) injection both contain the same active ingredient, exenatide, and should not be used together.
- Exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, based on postmarketing data. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON; consider other antidiabetic therapies for these patients.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.