Clarithromycin is prescribed for a skin infection. Which statin would most likely have a serious interaction with clarithromycin?

• A. Pravastatin
• B. Simvastatin
• C. Atorvastatin
• D. Rosuvastatin

Answer: (D)

Clarithromycin is a potent inhibitor of CYP3A4, the enzyme that metabolizes many statins. When a statin that relies heavily on CYP3A4 for clearance is taken with clarithromycin, the statin’s levels in the blood can rise significantly, increasing the risk of muscle toxicity such as myopathy or rhabdomyolysis.

Among common statins, those that depend most on CYP3A4 are simvastatin and atorvastatin. Because clarithromycin blocks the enzyme, these two would have the strongest interaction, leading to a higher risk of adverse muscle effects. Pravastatin and rosuvastatin, on the other hand, are not primarily cleared by CYP3A4; pravastatin is less dependent on hepatic metabolism and rosuvastatin is eliminated via multiple pathways with minimal CYP3A4 involvement. This makes their interactions with clarithromycin much less likely to be serious.

So, the key concept is that the severity of interaction hinges on how much the statin is metabolized by CYP3A4. Statins with strong CYP3A4 metabolism pose a higher risk with clarithromycin, whereas those with minimal CYP3A4 involvement, like rosuvastatin, pose a much lower risk. In practice, if macrolide therapy is needed, clinicians often avoid or adjust the dose of CYP3A4-metabolized statins and consider alternatives or temporary discontinuation.