Statins and Cytochrome P450 Inhibitors May Interact

Coadministration of certain statin drugs with cytochrome P450-3A4 (CYP3A4) inhibitors should be avoided.

"Although exceedingly well tolerated, treatment with statins incurs a small risk of myopathy or potentially fatal rhabdomyolysis, particularly when co-administered with medications that increase their systemic exposure," Dr. Terry A. Jacobson from Emory University School of Medicine notes.

He reports results from four small, short-term, parallel-group studies looking at the pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin, when coadministered with four CYP3A4 inhibitors (verapamil, mibefradil, itraconazole, and clarithromycin) in healthy adults.

Taken together, the studies demonstrate that these inhibitors "elicit profound increases in the systemic exposures of the lipophilic statins simvastatin and atorvastatin and their active metabolites."

In contrast, he observes, pravastatin, which is a hydrophilic non-CYP substrate that has no active metabolites, "exhibits a neutral pharmacokinetic interaction profile with respect to CYP substrates."

Earlier this month, Britain’s Medicines and Healthcare Products Regulatory Agency issued a bulletin reminding clinicians about potential statin drug interactions.
Am J Cardiol 2004;94:1140-1146.

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