Drug Interactions Newsletter

Volume 1, Issue 40, 10/20/2009

Question

Why is the HMG CoA reductase inhibitor (statin), specifically fluvastatin (Lescol®; Lescol XL®) considered to be safer in combination with cyclosporine (Gengraf®; Neoral®; Sandimmune®) compared to other statins in the treatment of hyperlipidemia?

Answer

The use of immunosuppressive drugs such as 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).  Unfortunately, statin drug concentrations, other than fluvastatin, coadministered along with cyclosporine have been known to be increased by 2.5 - 12 fold in the serum.(6-12)  This can put some patients at increased risk for myalgias, myositis, rhabdomyolysis and hepatotoxicity since these side effects are concentration or drug exposure dependent.(13,14) 

Though many of these statins have been used safely for the management of hyperlipidemia in post-organ transplantation patients on cyclosporine, fluvastatin has always been considered to be one of the safest in this population.  Some clinicians think that pravastatin is the safest or least likely to interact with cyclosporine since it...

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