Lovastatin and simvastatin are extensively metabolised by CYP3A4 so that drugs that inhibit this enzyme can cause marked rises in statin levels. Atorvastatin is also metabolised by CYP3A4, but to a lesser extent than lovastatin or simvastatin. Fluvastatin is metabolised primarily by CYP2C9, rosuvastatin by CYP2C9 and CYP2C19, while the cytochrome P450 system does not appear to be involved in the metabolism of pravastatin. Therefore the statins tend to interact differently. In order to reduce the risk of myopathy the CSM in the UK advises that statins should be used with care in patients who are at increased risk of this adverse effect, such as those taking interacting drugs. They also recommend that patients should be made aware of the risks of myopathy and rhabdomyolysis, and asked to promptly report muscle pain, tenderness or weakness, especially if accompanied by malaise, fever or dark urine.
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