Clarithromycin is a strong CYP3A4 inhibitor, and simvastatin and lovastatin depend heavily on CYP3A4 for clearance. Together, statin levels rise several-fold and the risk of myopathy and rhabdomyolysis rises with them; the combination is contraindicated in UK and US labelling.
For a short antibiotic course, the simplest option is to pause the statin. Alternatives are an antibiotic without CYP3A4 inhibition, such as azithromycin, or a statin less dependent on CYP3A4, such as pravastatin or rosuvastatin. Atorvastatin is affected to a lesser degree; a lower dose or a pause is reasonable.
- Pause simvastatin or lovastatin for the duration of a clarithromycin course.
- Consider azithromycin instead where it treats the infection equally well.
- Check for itraconazole, ketoconazole and HIV protease inhibitors, which carry the same risk.
- Tell the patient to report muscle pain, weakness or dark urine.
Why it matters
It is one of the commonest preventable interaction harms in primary care prescribing.
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