Drug Interaction Report

GENERALLY AVOID: There is some theoretical concern regarding the potential for additive musculoskeletal toxicity during coadministration of daptomycin and other drugs associated with myopathy, such as fibric acid derivatives. In animals, daptomycin has been associated with skeletal muscle effects characterized by degenerative/regenerative changes and variable elevations in creatine phosphokinase (CPK). Elevations in serum CPK were also reported more frequently in daptomycin-treated patients than in comparator-treated patients (2.8% vs. 1.8%) in phase 3 clinical trials. Similarly, fibrates are known to occasionally cause myopathy manifested as muscle pain and/or weakness in association with grossly elevated levels of CPK. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria. Myopathy has not been reported in clinical trials of daptomycin.

MANAGEMENT: Due to the limited nature of existing data, consideration should be given to temporarily suspending use of fibrates 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).