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FDA Issues Warning For Byetta

There was a great deal of hubbub when the FDA asked Amylin Pharmaceuticals to notify prescribers about the small incidence of pancreatitis associated with Byetta®(exenatide). As usual the lay press and many medical papers went for sensationalism and overreacted. My intern Harine Sampaio, Doctor of Pharmacy Candidate, University of Florida College of Pharmacy, reviewed all the real literature and has prepared a great report of what this really means.

FDA Issues Warning For Byetta®

Harine Sampaio, Doctor of Pharmacy Candidate,

University of Florida College of Pharmacy

 

An FDA warning in October 2007 has raised concerns on the drug Byetta® possibly being involved in case reports of acute pancreatitis. Byetta®(exenatide), made by Amylin Pharmaceuticals, Inc., is a synthetic form of exendin-4, a 39-amino acid peptide isolated from the salivary gland venom of the Gila monster lizard (heloderma suspectum).

The venom of Gila monsters has previously been found to be the cause of pancreatitis in victims of Gila monster bites due to overstimulation of the pancreas. Byetta® mimics the human incretin hormone, glucagon-like-peptide-1 (GLP-1), by enhancing glucose-dependent insulin secretion by the pancreatic beta-cells, suppressing elevated glucagon secretion by the liver and slowing gastric emptying. Approved by the FDA in April of 2005, Byetta® is indicated for use in type II diabetes as adjunctive therapy with metformin, a sulfonylurea, a thiazolidinedione or a combination of metformin and a sulfonylurea or a thiazolidinedione.1

Since its approval in 2005, Byetta® has been used by about 700,000 people worldwide. Although it is hard to predict the long term effects of this therapy, Byetta® seems to be well tolerated and its connection with acute pancreatitis needs to be confirmed in the coming years.

The October FDA alert comes in response to 30 post-marketing reports of acute pancreatitis in patients taking Byetta®. Of the 30 patients, 27 had at least one other risk factor for developing acute pancreatitis such as gallstones, severe hypertriglyceridemia, and alcohol use. Six of the patients experienced worsening of the symptoms of pancreatitis when the dose of Byetta® was increased from 5 micrograms (mcg) twice daily to 10 mcg twice daily. In addition, 22 of the 30 cases reported improvement in symptoms after Byetta® was discontinued and in three reports the symptoms of acute pancreatitis returned when Byetta® was restarted.2

In 2006, the journal Diabetes Care described a case report involving a 69 year-old male with type II diabetes. The subject developed abdominal pain within 24 hours of starting therapy with Byetta® and was admitted to the emergency room with pancreatitis on the fifth day of therapy. Symptoms of pancreatitis were resolved followed by discontinuation of Byetta® and initiation of appropriate therapy for pancreatitis. 3

Although the report described above as well as the majority of the FDA case reports show that pancreatitis symptoms were resolved upon discontinuation of Byetta®, it is hard to establish a causal relationship between the drug and this condition.  Post-marketing reports are voluntary and therefore lack control of both data and subjects.

Another drug with similar actions to Byetta®, Liraglutide, is currently under development by Novo Nordisk. This drug is a genetically modified version of the human hormone GLP-1 and has similar actions and side effect profile as Byetta. Phase III clinical trials of Liraglutide have so far failed to show an increased risk of acute pancreatitis with the use of the drug. So far, the most common side effects found are nausea and weight loss. The clinical effectiveness of Liraglutide is being evaluated in a series of clinical trials as part of the Liraglutide Effect and Action in Diabetes (LEAD) program.4,5                              

Adverse effects commonly associated with Byetta® include nausea, vomiting, diarrhea, indigestion and hypoglycemia (when used with a sulfonylurea) 1. The risk of developing gastrointestinal adverse effects increases in those with end-stage renal disease, dialysis, or severe renal impairment since Byetta® is predominantly excreted by the kidneys through glomerular filtration 1.  Healthcare professionals should use caution when prescribing Byetta® to patients at high risk for pancreatitis and to those taking agents known to cause pancreatitis.

Harine Sampaio received her Dietetics degree from Florida State University in 2004. She is currently working to receive her Doctor of Pharmacy degree from University of Florida. Originally from Brazil, Harine has lived in Florida for the past 10 years. She lives in St Petersburg with her husband and son, and upon graduation plans to work for Walgreens as a community pharmacist.

References:

  1. Product Information: BYETTA(R). http://www.fda.gov/cder/foi/label/2007/021773s007lbl.pdf

  2. Information for healthcare professionals Exenatide (marketed as Byetta)

http://www.fda.gov/cder/drug/InfoSheets/HCP/exenatideHCP.htm
                3.  Diabetes Care 29, 2006
                                http://www.amylin.com/InvestorDocs/DiabetesCareJournal.pdf

  1. Novo Nordisk Press Release

 http://press.novonordisk-us.com/internal.aspx?rid=393

  1. Drug Development Technology

http://www.drugdevelopment-technology.com/projects/liraglutide/