Drug Interaction Report

GENERALLY AVOID: There is the potential for additive musculoskeletal toxicity during coadministration of daptomycin and HMG-CoA reductase inhibitors. Cases of rhabdomyolysis have been reported with concomitant administration of simvastatin and daptomycin. This may be due to additive musculoskeletal toxicity as both HMG-CoA reductase inhibitors and daptomycin have caused myopathy and rhabdomyolysis when given alone.

MANAGEMENT: Use of HMG-CoA reductase inhibitors should be temporarily suspended in patients receiving daptomycin. All patients receiving daptomycin should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. CPK levels should be monitored weekly, and patients who develop unexplained elevations in CPK should be monitored more frequently. Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK levels exceeding 1000 U/L (approximately 5 times the upper limit of normal), or in patients without reported symptoms who have marked elevations in CPK (10 times the upper limit of normal, or more).

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.