Association of Ezetrol (ezetimibe) With Myalgia, Rhabdomyolysis, Hepatitis, Pancreatitis And ThrombocytopeniaFeb 1, 2005 | Health Canada Dear Health Care Professional,
Merck Frosst/Schering Pharmaceuticals, following discussions with Health Canada, would like to inform you of new safety data for Ezetrol(ezetimibe), used alone or in combination with a statin. Ezetimibe is a cholesterol absorption inhibitor that is classified as a systemic drug, because of the enterohepatic recirculation of one of its metabolites1.
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 Warnings, Precautions, and Adverse Events sections are being updated to reflect the occurrence of the following adverse events in patients taking Ezetrol(ezetimibe) alone or in combination with a statin: myalgia; rhabdomyolysis; hepatitis; acute pancreatitis; thrombocytopenia; and suspected interaction between Ezetrol(ezetimibe) and warfarin.
While it is not possible to definitively establish a causal relationship between these adverse events and the use of Ezetrol (ezetimibe), the Product Monograph changes and the following recommendations are based on the potentially serious nature of these events.
Adverse muscle events:
Myalgia has been reported in patients treated with Ezetrol (ezetimibe).
Importantly, a number of patients treated with Ezetrol(ezetimibe) in whom myalgia occurred, had previously experienced myalgia (with or without elevated CK levels) with statin therapy. 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 treated with Ezetrol(ezetimibe), 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.
Adverse hepatic events:
Elevations of liver transaminases and cases of hepatitis have been reported in patients treated with Ezetrol (ezetimibe). Liver function monitoring is recommended when therapy with Ezetrol(ezetimibe) is initiated in patients treated or about to begin treatment with a statin.
Health care professionals should be aware that the use of Ezetrol(ezetimibe) in combination with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations of liver transaminases.
Care should be exercised in the use of Ezetrol (ezetimibe) in patients with active liver disease or unexplained persistent elevations of liver transaminases.
Adverse pancreatic events:
Physicians should consider the diagnosis of pancreatitis in patients who develop sudden acute abdominal pain during therapy with Ezetrol(ezetimibe).
Suspected interaction between Ezetrol (ezetimibe) and warfarin:
Additional International Normalized Ratio (INR) measurements are recommended in patients treated with warfarin, and in whom Ezetrol(ezetimibe) is initiated.