Drug Interactions between dirithromycin and pravastatin

MONITOR: Coadministration with macrolide antibiotics may increase the risk and severity of musculoskeletal toxicity during pravastatin therapy. Some macrolides like clarithromycin and erythromycin have been reported to increase pravastatin exposures, presumably by inhibiting the hepatic uptake of pravastatin via organic anion transporting polypeptide (OATP) 1B1 and 1B3. Other macrolides like azithromycin are not known to be inhibitors of OATP1B1/1B3 but may have the potential to increase pravastatin exposures according to some manufacturers. 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 with the use of statins. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Caution is advised when pravastatin is prescribed with macrolide antibiotics. The lowest effective dosage of pravastatin is recommended. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise, and/or dark colored urine. Pravastatin should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.