A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.

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Floyd JS, Kaspera R, Marciante KD, Weiss NS, Heckbert SR, Lumley T, Wiggins KL, Tamraz B, Kwok PY, Totah RA, Psaty BM

A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.

Clin Pharmacol Ther. 2012 May;91(5):896-904. doi: 10.1038/clpt.2011.295. Epub 2012 Mar 14.

PubMed ID

22419147 [ View in PubMed

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Abstract

An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Amlodipine	Cytochrome P450 2C8	Protein	Humans	Unknown	Inhibitor	Details