Drug Interactions Corner

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Interaction Between Atorvastatin and Clopidogrel Illustrates Challenges with 3A4 System

KEY POINT

Atorvastatin (Lipitor—Pfizer) competitively inhibits the activation of clopidogrel (Plavix—Sanofi Synthélabo; Bristol-Myers Squibb) by the cytochrome P450 3A4 system (CYP3A4), decreasing effectiveness of the platelet inhibitor. The interaction has implications for other medications that induce or inhibit the CYP3A4 isoenzymes. Patients with acute coronary syndromes—most of whom receive stents—are at risk for negative outcomes as a result of this interaction.

SOURCES

Lau WC et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation. Circulation. 2003;107:32–7.

Savi P et al. The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A. Thromb Haemost. 1994;72:313–7.