Methotrexate and trimethoprim interaction


Advice to all GP practices, out of hours providers, urgent care and community pharmacies.

Concomitant use of methotrexate and trimethoprim and trimethoprim combination products (e.g. co-trimoxazole (Septrin®), even in low doses, can result in serious systemic toxicity characterized by pancytopenia, oral mucositis, and nephrotoxicity.

All prescribers and dispensers should be mindful of this and other potential drug interactions with the introduction of new prescription or non-prescription medications.

This interaction is potentially hazardous, even with short courses or low doses of trimethoprim

Bone marrow suppression can occur abruptly, leading to:

  • Life-threatening infection as the body cannot produce leukocytes in response to invading bacteria and viruses
  • Anaemia due to a lack of red blood cells
  • Spontaneous severe bleeding due to a deficiency of platelets

 Fatalities Have Occurred

Key safety points:

  • Never prescribe/dispense trimethoprim, not even a short course or a low dose, to patients receiving methotrexate
  • Double check to make sure methotrexate is not already prescribed by a hospital doctor (and if it is, add it to the patient’s electronic practice records)
  • Flag the interaction as potentially extremely serious on your computer system
  • Make sure that all patients on methotrexate have patient-held recording document

Be aware that:

  • some information sources do not stress the importance of this interaction
  • co-trimoxazole (Septrin®) contains trimethoprim

Advice for pharmacists and dispensing staff:

  • Request sight of the patient-held recording document and check if any dose changes have been made since last prescription issue; this is to double check in case prescribing systems have not been updated post-test review.
  • Always check for drug interactions. If a drug interaction is identified, ensure that the prescriber is made aware before dispensing. 
  • The strength of tablet supplied to the patient must remain consistent to prevent any confusion for the patient over the number of tablets they need to take.  It is recommended that only 2.5mg tablets are prescribed.
Pharmacists should query any prescriptions for the 10mg tablets.
This alert was originally issued by North Tyne LPC but it is equally applicable here, so the alert is repeated with acknowledgement to them.