Exenatide drug label to include information on post-marketing surveillance of altered kidney function

Key Points

In early November 2009, FDA approved revisions to the drug label for exenatide (Byetta, Amylin Pharmaceuticals), an injectable glucagon-like peptide-1 agonist for the treatment of type 2 diabetes mellitus. The changes included the addition of information pertaining to the increased risks of altered renal function associated with exenatide use. This action comes just as Eli Lilly and Company and Amylin received additional approval from FDA to market exenatide as monotherapy along with diet and exercise for the treatment of type 2 diabetes.

Nearly 7 million prescriptions for exenatide have been written since the drug's initial FDA approval in 2005.The current American Diabetes Association treatment guidelines consider exenatide a "Tier 2" therapy, suggesting it follow the use of other hypoglycemic agents including metformin, sulfonylureas and insulin.

REPORTING SYSTEM AT WORK

While an FDA press release stressed that the label revisions were needed because of "the serious potential consequences of altered kidney function and temporal relationship between the development of renal effects and initiation of exenatide" FDA officials also noted, "The 78 cases represent a small percentage of the total number of patients using the drug to control blood sugar levels."

The FDA press release also points out that the majority of patients, 74 of 78 (95%), had at least one pre-existing risk factor for altered kidney function, such as cardiac insufficiency, hypertension, pancreatitis, rhabdomyolysis, or urinary tract infection, as well as concomitant medications such as antiretrovirals, antihypertensives, diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs). Forty-two patients (54%) reported symptoms associated with volume depletion, such as diarrhea, and/or vomiting, which are the most commonly reported adverse events associated with the use of exenatide, and also known risk factors for developing renal dysfunction.

Despite these other potential contributing explanations, Amy Egan, MD, MPH, of the Division of Metabolism and Endocrinology Products at FDA's Center for Drug Evaluation and Research suggests, "Healthcare professionals and patients taking Byetta should pay close attention to any signs or symptoms of kidney problems."

These would include increased serum creatinine, changes in urination, unexplained swelling in the extremities, increases in blood pressure, lethargy, changes in appetite or digestion, or dull ache in the mid to lower back.

Other recommendations to healthcare professionals in the revised drug label include a warning against using exenatide in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease, as well as a precautionary statements regarding initiation or increasing doses of exenatide from 5 µg to 10 µg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min) and discontinuing exenatide if kidney dysfunction cannot be explained by other causes.

SOURCES

Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32:193-203.

Amylin Pharmaceuticals, Inc. Byetta (exenatide) prescribing information; 2009. San Diego, CA. Available at: http://www.byetta.com/index.jsp/. Accessed November 4, 2009.

FDA. Information for Healthcare Professionals: Reports of Altered Kidney Function in patients using Exenatide (Marketed as Byetta). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm188656.htm . Accessed November 4, 2009.