Medication Adverse Event Alert

October 16, 2007

ISSUE:	FDA announces additions to the PRECAUTIONS section of exenatide due to postmarketing reports of acute pancreatitis in patients taking exenatide
MEDICATION:	Byetta® (exenatide), 250mcg/ml, 1.2ml pen, 5mcg/dose

The following was posted on FDA Med Watch alert website dated October 16, 2007:

"FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta (exenatide), a drug used to treat adults with type 2 diabetes. An association between Byetta and acute pancreatitis is suspected in some of these cases. Amylin Pharmaceuticals, Inc. has agreed to include information about acute pancreatitis in the PRECAUTIONS section of the product label.

Healthcare professionals should be alert to the signs and symptoms of acute pancreatitis and instruct patients taking Byetta to seek prompt medical care if they experience unexplained, persistent, severe abdominal pain which may or may not be accompanied by vomiting. If pancreatitis is suspected, Byetta should be discontinued. If pancreatitis is confirmed, Byetta should not be restarted unless an alternative etiology is identified"

An excerpt of the accompanying "Information for Healthcare Professionals" stated the following:

• Healthcare providers should be alert to the signs and symptoms of acute pancreatitis. Symptoms include persistent severe abdominal pain that can radiate to the back and may be accompanied by nausea and vomiting. Acute pancreatitis is typically confirmed by the presence of elevated levels of serum amylase and/or lipase and characteristic findings by radiological imaging.
• Discontinue Byetta if pancreatitis is suspected. If pancreatitis is confirmed, do not restart Byetta unless an alternative etiology for the pancreatitis is identified.

Information for the patient: Physicians who prescribe Byetta should discuss with their patients: Byetta is a medicine given by injection to help treat adults with type 2 diabetes. Commonly reported side effects of Byetta include nausea, vomiting, diarrhea, indigestion and upper abdominal discomfort. However, the presence of unexplained, severe abdominal pain, with or without nausea and vomiting, raises the suspicion of acute pancreatitis, a potentially serious condition that requires prompt medical attention. Therefore, patients taking Byetta should promptly seek medical care if they experience unexplained severe abdominal pain with or without nausea and vomiting.

Background Information and Data

FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients treated with Byetta. Twentyseven of the 30 patients had at least one other risk factor for acute pancreatitis such as gallstones, severe hypertriglyceridemia, and alcohol use. In six patients the symptoms of pancreatitis began or worsened soon after the dose of Byetta was increased from 5 micrograms twice daily to 10 micrograms twice daily. Twentyone patients were hospitalized. There were no reports of hemorrhagic or necrotizing pancreatitis. However, five patients developed serious complications including dehydration and renal failure; suspected ileus; phlegmon; and ascites. Twenty-two of the 30 reports indicated that the patients improved after discontinuing Byetta.

Details in three reports indicated that the symptoms of acute pancreatitis returned when Byetta was restarted. Nausea and vomiting returned in two patients when Byetta was restarted. In a third patient, abdominal pain returned when Byetta was restarted and abated after Byetta was permanently discontinued.