Exenatide

BYETTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • BYETTA contains exenatide. Coadministration with other exenatide-containing products is not recommended. BYETTA (exenatide) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Coadministration with other exenatide-containing products is not recommended.

Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. BYETTA is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The amino acid sequence of exenatide partially overlaps that of human GLP-1. Exenatide has been shown to bind and activate the human GLP-1 receptor in vitro. This leads to an increase in both glucose-dependent synthesis of insulin, and in vivo secretion of insulin from pancreatic beta cells, by mechanisms involving cyclic AMP and/or other intracellular signaling pathways.

• Inject subcutaneously within 60 minutes prior to morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). • Initiate at 5 mcg per dose twice daily, increase to 10 mcg twice daily after 1 month based on clinical response.

BYETTA is contraindicated in patients with: • A prior severe hypersensitivity reaction to exenatide or to any of the excipients in BYETTA. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with BYETTA. • A history of drug-induced immune-mediated thrombocytopenia from exenatide products. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use. • History of severe hypersensitivity to exenatide or any of the excipients in BYETTA. • History of drug-induced immune-mediated thrombocytopenia from exenatide products.

• Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including BYETTA. Discontinue if pancreatitis is suspected. • Never share a BYETTA pen between patients, even if the needle is changed. • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Reduction in the dose of insulin secretagogues or insulin may be necessary. • Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. • Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. BYETTA is not recommended in patients with severe gastroparesis.

The following serious adverse reactions are described below or elsewhere in the prescribing information: • Acute Pancreatitis • Never Share a BYETTA Pen Between Patients • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin • Acute Kidney Injury Due to Volume Depletion • Severe Gastrointestinal Adverse Reactions • Immunogenicity • Hypersensitivity • Drug-Induced Thrombocytopenia • Acute Gallbladder Disease • Pulmonary Aspiration During General Anesthesia or Deep Sedation • Most common (≥5%) and occurring more frequently than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation, asthenia. Nausea usually decreases over time.

• May impact absorption of orally administered medications. • Warfarin: Postmarketing reports of increased INR sometimes associated with bleeding. Monitor INR frequently until stable upon initiation or alteration of BYETTA therapy. Generic Section Table 6: Clinically Relevant Interactions with BYETTA Concomitant Use of Insulin Secretagogues or Insulin Clinical Impact Exenatide promotes insulin release from pancreatic beta-cells in the presence of elevated glucose concentrations. The risk of hypoglycemia is increased when exenatide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Intervention When initiating BYETTA, consider reducing the dose of concomitantly administered insulin secretagogue or insulin to reduce the risk of hypoglycemia. Warfarin Clinical Impact In a drug interaction study, BYETTA did not have a significant effect on INR.

Store BYETTA in the refrigerator at 36°F to 46°F (2°C to 8°C). • After first use, BYETTA can be kept at a temperature not to exceed 77°F (25°C). • Do not freeze.