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.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.