Cholestad Special Precautions

Muscle Effects: Simvastatin and other inhibitors of HMG-CoA reductase occasionally causes myopathy, which is manifested as muscle pain or weakness with grossly elevated creatine kinase (CK) >10 times the upper limit of normal (ULN).
Myopathy Caused by Drug Interactions: The incidence and severity of myopathy are increased by concomitant use of HMG-CoA reductase inhibitors with drugs that can cause myopathy when given alone eg, gemfibrozil, fibrates.
Simvastatin and HMG-CoA reductase inhibitors eg, cyclosporins, mibefradil, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin are metabolized by the cytochrome P-450 isoform 3A4.
Certain drugs that have a significant inhibitory effect at the therapeutic doses on this metabolic pathway can substantially raise the plasma levels of HMG-CoA reductase inhibitors and thus increase the risk of myopathy. Patients starting therapy with Simvastatin should be advised of the risk of myopathy and told to report promptly.
Hepatic Effect: If the transaminase levels show evidence of progression particularly if they rise to 3 times the ULN and are persistent, Cholestad should be discontinued. It is recommended that liver function tests be performed before treatment begins and periodically thereafter. Patients titrated to the 80-mg dose should receive an additional test at 3 months. Cholestad should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.