methotrexate and co-trimoxazole

ContraindicatedDo not co-prescribe these two.

Mechanism

Both methotrexate and co-trimoxazole interfere with folate metabolism. Methotrexate inhibits dihydrofolate reductase (DHFR), while trimethoprim also inhibits DHFR and sulfamethoxazole inhibits dihydropteroate synthase, leading to sequential blockade. Additionally, trimethoprim reduces renal tubular secretion of methotrexate, decreasing its clearance and increasing plasma concentrations.

What it means clinically

Additive antifolate and pharmacokinetic effects can cause severe, potentially fatal bone marrow suppression leading to pancytopenia, mucositis, and hepatotoxicity. Manifestations include anaemia, leukopenia, thrombocytopenia, and infections.

What to do

Co-prescription is contraindicated. Avoid concurrent use. If absolutely necessary, use alternative antibiotics with no antifolate activity. Monitor full blood count and methotrexate levels frequently if co-administration is unavoidable.

Evidence

Widely recognised interaction with numerous case reports and clinical guidelines. Several national formularies list this as contraindicated.

The two drugs

methotrexateantimetabolite immunosuppressantRead the monograph co-trimoxazolesulfonamide antibioticRead the monograph

Practise prescribing around interactions like this one

Oskela marks prescriptions against this interaction database automatically: write a chart for a simulated patient and every clash is caught and explained.

Try a prescription, no account Create a free account

Other interactions involving methotrexate or co-trimoxazole

Educational reference for students and clinicians in training. It does not replace professional judgement, local protocols or current prescribing information.