Canada - Health Canada and the manufacturer of ezetimibe (Ezetrol®), have provided new safety data on this cholesterol absorption inhibitor, used alone or in combination with a statin, because of the entero-hepatic recirculation of one of its metabolites (1). The Product Monograph for Ezetrol® (ezetimibe) has been updated to include information from international post-marketing reports of rare, and in some cases serious, adverse events. The Patient Information section is being updated to inform patients of the signs and symptoms of hepatic, muscle, and pancreatic adverse events, for which early consultation with a physician is recommended. Additional reports of myalgia, many accompanied by elevated creatine phosphokinase (CK) values, have been reviewed by Health Canada.
The following adverse events have occurred in patients taking ezetimibe alone or in combination with a statin: myalgia; rhabdomyolysis; hepatitis; acute pancreatitis; thrombocytopenia; and suspected interaction with warfarin.
• Patients with a history of statin intolerance(myalgia with or without elevated CK levels) should be closely monitored for adverse muscle events during treatment with Ezetrol® (ezetimibe).
• Patients who experience persistent muscle pain should be instructed to contact their physicians for evaluation of the possibility of rhabdomyolysis. In most reported cases, rhabdomyolysis resolved when the drugs were discontinued.
• Liver function monitoring is recommended. The use of ezetimibe in combination with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations of liver transaminases.
• Physicians should consider the diagnosis of pancreatitis in patients who develop sudden acute abdominal pain during therapy.
• Additional international normalized ratio (INR) measurements are recommended in patients treated with warfarin.
Reference: Communication from Merck Frosst/Schering Pharmaceuticals dated 1 February 2005 posted by Health Canada at http://www.hc-sc.gc.ca