Trexol Drug Interactions

Methotrexate is extensively protein bound and may be displaced by certain drugs such as salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, and the acidic anti-inflammatory agents, so causing a potential for increased toxicity when used concurrently.
Concomitant use of other drugs with nephrotoxic or hepatotoxic potential (including alcohol) should be avoided.
Vitamin preparations containing folic acid or its derivatives may decrease the effectiveness of methotrexate.
Caution should be used when NSAIDs and salicylates are administered concomitantly with methotrexate. These drugs have been reported to reduce the tubular secretion of methotrexate and thereby may enhance its toxicity.
Concomitant use of NSAIDs and salicylates has been associated with fatal methotrexate toxicity.
However, patients using constant dosage regimens of NSAIDs have received concurrent doses of methotrexate without problems observed.
Treatment with more than one DMARD in various regimens is being tried but there is little evidence available to assess benefit. A meta-analysis of 5 different combinations of DMARDs demonstrated that although efficacy might be greater than single DMARDs, toxicity was also increased.
Renal tubular transport is also diminished by probenecid and penicillins; use of these with methotrexate should be carefully monitored.
A potential interaction may exist between methotrexate and proton-pump inhibitors (e.g. omeprazole, pantoprazole). Omeprazole may inhibit methotrexate clearance resulting in potentially toxic methotrexate levels.
Severe bone marrow depression has been reported following the concurrent use of methotrexate and co-trimoxazole or trimethoprim. Concurrent use should probably be avoided.
The use of nitrous oxide potentiates the effect of methotrexate on folate metabolism, yielding increased toxicity such as severe, unpredictable myelosuppression and stomatitis and in cases of intrathecal administration increased severe, unpredictable neurotoxicity. Whilst this effect can be reduced by administering calcium folinate, the concomitant use of nitrous oxide and methotrexate should be avoided (see Dosage & Administration).
An increased risk of hepatitis has been reported following the use of methotrexate and the acitretin metabolite, etretinate. Consequently, the concomitant use of methotrexate and acitretin should be avoided.
Methotrexate may increase the bioavailability of mercaptopurine by interference with first-pass metabolism.
Concomitant application of methotrexate and theophylline can reduce theophylline clearance.