'Fire and forget?' - pharmacological considerations in coronary care

The potential risk of drug-drug interactions is often overlooked during drug therapy selection. Multiple risk factors for drug-drug interactions exist in both the acute and chronic phases of acute coronary syndrome (ACS), including concomitant medications and underlying diseases. Some statins have been used for secondary prevention of coronary heart disease (CHD) in these patients and are not all equivalent in their susceptibility to drug-drug interactions. The lipophilic drugs lovastatin, simvastatin, atorvastatin, cerivastatin and fluvastatin are metabolized via the cytochrome P450 (CYP450) system in the liver and the gut, making them subject to potential interactions with concomitantly administered drugs that are competing for metabolism via this system. Clinically important interactions with simvastatin or lovastatin and drugs that inhibit the 3A4 isoenzyme (part of the CYP450 system) may result in myopathy and rhabdomyolysis, which can be fatal. However, pravastatin is water-soluble, it does not undergo metabolism via CYP450 to any significant extent (< 1%), is excreted essentially unchanged and has not been shown to participate in any clinically relevant drug-drug interactions with CYP450 agents. When selecting drug therapy, knowledge of a drug's route of metabolism is important to predict and prevent life-threatening drug-drug interactions. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.