Early Communication About an Ongoing Safety Review of Ezetimibe/Simvastatin (marketed as Vytorin), Simvastatin (marketed as Zocor) and Ezetimibe (marketed as Zetia)

FDA Investigates a Report from the SEAS Trial

Update 8/21/2008: This information reflects FDA’s current analysis of available data concerning these drugs.  Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue.  Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering but has not reached a conclusion about whether this information warrants any regulatory action.  FDA intends to update this document when additional information or analyses become available. 

FDA is investigating a report from the SEAS trial (Simvastatin and Ezetimibe in Aortic Stenosis) of a possible association between the use of Vytorin (a combination of simvastatin plus ezetimibe) and a potentially increased incidence of cancer.  Simvastatin (Zocor), a “statin” class drug approved in 1991, decreases production of cholesterol by the liver and is indicated to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events such as heart attack and stroke. Ezetimibe (Zetia), approved in 2002, inhibits the absorption of cholesterol in the intestine and is indicated to reduce LDL-cholesterol levels. Vytorin, the combination product approved in 2004, is indicated to reduce LDL-cholesterol levels.

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Information for Healthcare Professionals: Exenatide (marketed as Byetta)

Update 8/18/2008:  Since issuing Information for Healthcare Professionals in October 2007, FDA has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Byetta is a medicine given by subcutaneous injection to help treat adults with type 2 diabetes. Of the 6 cases of hemorrhagic or necrotizing pancreatitis, all patients required hospitalization, two patients died and four patients were recovering at time of reporting.  Byetta was discontinued in all 6 cases.   

Byetta and other potentially suspect drugs should be promptly discontinued if pancreatitis is suspected.  There are no signs or symptoms that distinguish acute hemorrhagic or necrotizing pancreatitis associated with Byetta from the less severe form of pancreatitis.  If pancreatitis is confirmed, initiate appropriate treatment and carefully monitor the patient until recovery.  Byetta should not be restarted.  Consider antidiabetic therapies other than Byetta in patients with a history of pancreatitis.

Update 8/8/2008:  The FDA is notifying the public of the risk of a rare condition of muscle injury called rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. A revision of the simvastatin labeling in 2002 described an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses greater than 20 mg daily. However, the FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin, particularly with simvastatin doses greater than 20 mg daily. Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone.