Drug Interaction Report

MONITOR: Coadministration with drugs that are eliminated by active tubular secretion may delay and/or decrease the clearance of pemetrexed. The mechanism is competitive inhibition of the renal excretion of pemetrexed, which is primarily eliminated unchanged via glomerular filtration and active tubular secretion. Drugs (and/or their metabolites) that are thought to undergo active tubular secretion include acyclovir, allopurinol, aminosalicylic acid, cidofovir, cimetidine, creatine, dyphylline, famciclovir, famotidine, flecainide, ganciclovir, levetiracetam, metformin, methotrexate, midodrine, mycophenolic acid, oseltamivir, pralatrexate, probenecid, procainamide, quinidine, ranitidine, tenofovir, triamterene, trimethoprim, valacyclovir, valganciclovir, zalcitabine, zidovudine, and many of the beta-lactam and quinolone antibiotics.

MANAGEMENT: Patients receiving pemetrexed in combination with other drugs that undergo active tubular secretion should be monitored for excessive pharmacologic effects of one or both drugs, and the dosages of the drugs adjusted if necessary. The potential for increased toxicity of pemetrexed such as bone marrow suppression should be considered. Renal function should be closely monitored during therapy. Pemetrexed should not be administered to patients whose creatinine clearance is below 45 mL/min.

ADJUST DOSING INTERVAL: Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.

MANAGEMENT: Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.