Simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time , reported as International Normalized Ratio (INR), increased from a baseline of to and from to in a normal volunteer study and in a hypercholesterolemic patient study, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting VYTORIN and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of VYTORIN is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), % of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (%), myalgia (%), and arthralgia (%). The most commonly reported adverse reactions (incidence ≥5%) in Simvastatin controlled clinical trials were: upper respiratory infections (%), headache (%), abdominal pain (%), constipation (%), and nausea (%).