Drug Interactions between celecoxib / tramadol and daptomycin

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

MONITOR: The concomitant administration of daptomycin and other nephrotoxic drugs or drugs that reduce renal filtration may result in additive renal effects and/or increased plasma levels of daptomycin. Daptomycin has been associated with renal impairment, although causality has not been determined. Increased plasma concentrations of daptomycin may increase the risk of myopathy. The risk may be increased in patients with pre-existing renal dysfunction.

MANAGEMENT: Serum drug concentrations and renal function, including serum creatinine, should be carefully monitored during concurrent administration. In addition, 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).