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Methotrexate is extensively protein bound and may be displaced by certain drugs (1) and so resulting in a potential for increased toxicity when used concurrently:

  • salicylates, sulphonamides, hypoglycaemics, diuretics, diphenylhydantoins, chloramphenicol, tetracyclines, p-aminobenzoic acid, the acidic anti-inflammatory drugs

Renal tubular transport is reduced by penicillins and probenecid and use of methotrexate with these drugs should be carefully monitored.

Non-steroidal ant-inflammatory drugs (NSAIDs) should not be administered prior to, or concomitantly with, HIGH dose methotrexate as fatal methotrexate toxicity has been reported (1). Caution is also advised when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate (1).

Methotrexate should be used with caution in patients taking drugs with an anti-folate potential (e.g. co-trimoxazole, nitrous oxide) because of reported cases of acute megaloblastic anaemia and pancytopenia that have been reported in rare cases.

Concomitant use of other drugs with hepatotoxic or nephrotoxic potential should generally be avoided, unless considered clinically justified, in which case the patient should be closely monitored.

The summary of product characteristics must be consulted before prescribing this drug.

Reference:

  • Wyeth (February 2001). Methotrexate injection 25mg/ml and methotrexate 2.5mg tablets.

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