Increased hepatotoxicity during regular alcohol consumption or intake of liver-damaging medicines eg, azathioprine, leflunomide, retinoids. Increased toxicity w/ amidopyrine derivatives, para-aminobenzoic acid, barbiturates, doxorubicin, OCs, phenylbutazone, phenytoin, probenecid, salicylates, sulphonamides, tetracyclines & tranquillizers. Reduction in tubular secretion w/ para-aminohippuric acid, NSAIDs, probenecid, salicylates, sulphonamides & other weak organic acids. Increased serum conc w/ penicillins & sulphonamides. May impair efficacy in concomitant administration w/ vit preparations which contains folic acid or its derivatives. Increased plasma levels of mercaptopurines. May reduce the excretion of theophylline. Reduced absorption w/ oral antibiotics. Severe haematological & GI toxicity in concomitant administration w/ NSAIDs. Enhanced efficacy w/ sulfasalazine. Potentiated effect on folic acid metabolism w/ nitrogen monoxide base. Inhibited effect w/ L-asparaginase. Increased non-renal elimination w/ colestyramine. Pancytopenia w/ pyrimethamine or co-trimoxazole. Increased risk of impaired kidney function w/ procarbazine. Delayed or inhibited renal excretion w/ proton pump inhibitors (omeprazole, pantoprazole, lansoprazole). Increased risk of soft tissue or bone necrosis w/ radiotherapy. Increased nephrotoxicity w/ cisplatin.