Drug Interactions Newsletter

Volume 1, Issue 7, 03/03/2009

Question

How does cyclosporine (Gengraf®; Sandimmune®; Neoral®) cause a 5-12 fold increase in pravastatin (Pravachol®) concentrations even though pravastatin is not a substrate of the CYP450 enzyme system?

Answer

The prescribing of immunosuppressive drugs (in particular cyclosporine) for patients who have undergone organ transplantation is common and has led to improvements in rejection-related mortality.  However, as many as 80% of heart transplant and 60% of renal transplant patients will develop post-transplant dyslipidemia that is, in part, mediated by cyclosporine.(1-5)  Since immunosuppressive agents typically cannot be stopped or changed, patients will need lipid-lowering treatment with mortality reducing drugs like HMG CoA reductase inhibitors (i.e., statins).(2)  One statin with a profile that is perceived to be free of drug-drug interactions is pravastatin (Pravachol®).  This perception has developed as a result of pravastatin not being a substrate for any of the commonly known CYP450 isoenzymes found in the gastrointestinal tract and liver.......To read the full answer please LOGIN or SUBSCRIBE NOW.