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.