Zocor Warnings & Precautions

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Zocor - Warnings & Precautions [simvastatin]

Elevated transaminases resulted in the discontinuation of 8 patients from therapy in the simvastatin group (n= 2,221) and 5 in the placebo group (n= 2,223). Of the 1,986 simvastatin treated patients in 4S with normal liver function tests (LFTs) at baseline, only 8 (0. 4%) developed consecutive LFT elevations to > 3X ULN and/ or were discontinued due to transaminase elevations during the 5.4 years (median follow-up) of the study. Among these 8 patients, 5 initially developed these abnormalities within the first year. All of the patients in this study received a starting dose of 20 mg of simvastatin; 37% were titrated to 40 mg. In 2 controlled clinical studies in 1,105 patients, the 12-month incidence of persistent hepatic transaminase elevation without regard to drug relationship was 0.9% and 2.1% at the 40-and 80-mg dose, respectively.

No patients developed persistent liver function abnormalities following the initial 6 months of treatment at a given dose. It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. Patients titrated to the 80-mg dose should receive an additional test prior to titration, 3 months after titration to the 80-mg dose, and periodically thereafter (e. g., semiannually) for the first year of treatment.

Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality( ies) return to normal. Should an increase in AST or ALT of 3X ULN or greater persist, withdrawal of therapy with ZOCOR is recommended. The drug should be used with caution in patients who consume substantial quantities of alcohol and/ or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin. As with other lipid-lowering agents, moderate (less than 3X ULN) elevations of serum transaminases have been reported following therapy with simvastatin. These changes appeared soon after initiation of therapy with simvastatin, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.