Drug Interactions between clarithromycin and Pravachol

ADJUST DOSE: Coadministration with clarithromycin or erythromycin may increase the plasma concentrations of pravastatin and the risk of myopathy and rhabdomyolysis. The proposed mechanism is inhibition of the hepatic uptake of pravastatin via organic anion transporting polypeptide 1B1 and 1B3. In healthy volunteers, pravastatin peak plasma concentration (Cmax) increased by 128% and systemic exposure (AUC) increased by 110% when pravastatin (40 mg once daily for 8 days) was administered in combination with clarithromycin (500 mg twice daily for 9 days). Similarly, erythromycin has been reported to increase pravastatin Cmax by 121% and AUC by 70%. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: The benefits of using pravastatin in combination with clarithromycin or erythromycin should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. A lower dosage of pravastatin should be considered if concomitant use is required. The product labeling for pravastatin recommends that dosage not exceed 40 mg daily when used in combination with clarithromycin. No dosage recommendations are available for use with erythromycin. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

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