clarithromycin and simvastatin

Pharmacokinetic interaction: clarithromycin is a potent inhibitor of cytochrome P450 3A4 (CYP3A4). Simvastatin is extensively metabolised by CYP3A4 to active metabolites. Inhibition of CYP3A4 by clarithromycin markedly increases plasma concentrations of simvastatin and its metabolites, leading to an exaggerated pharmacological effect and increased risk of toxicity.

Co-administration of clarithromycin and simvastatin significantly increases the risk of myopathy and rhabdomyolysis, which can present with muscle pain, weakness, and elevated creatine kinase levels. Rhabdomyolysis may lead to acute renal failure and is potentially life-threatening. Because the interaction is predictable and severe, concurrent use is contraindicated.

Avoid co-prescription of clarithromycin and simvastatin. If an antibiotic is required, consider an alternative macrolide (e.g., azithromycin) or another antibiotic that does not inhibit CYP3A4. If a statin is required, consider a statin not metabolised by CYP3A4, such as pravastatin or rosuvastatin. If temporary combination is deemed absolutely necessary, simvastatin should be withheld during clarithromycin therapy; however, this approach is rarely acceptable given the contraindication.

Well-established interaction. Simvastatin prescribing information lists clarithromycin as a contraindicated co-medication. Numerous case reports and clinical studies confirm increased simvastatin exposure and rhabdomyolysis risk with CYP3A4 inhibitors. The interaction is consistent with the pharmacokinetic profile of simvastatin and clarithromycin.