Methotrexate and Bactrim – Important Drug Interaction

EJ is a 54-year-old female with a history of rheumatoid arthritis. She has been on methotrexate (with folic acid supplementation) for years with relatively few RA flares over the last 10 years. She was recently diagnosed with a urinary tract infection and was prescribed sulfamethoxazole/trimethoprim (Bactrim). What concerns should we have regarding the methotrexate and Bactrim drug interaction?

There are a couple of possible negative outcomes that could result from the drug interaction between methotrexate and Bactrim. The first concern is an increased risk of methotrexate toxicity. In particular, bone marrow suppression and increased immunosuppression are possible negative outcomes.

The other potential negative outcome is a reduction in folic acid levels. This could ultimately lead to deficiency. This interaction likely doesn’t concern me as much because the course of the antibiotic is likely to be short. The other reason I’m not as concerned is that the patient is already getting supplementation to help prevent folic acid deficiency.

Is this interaction severe enough to change therapy? What should be done when addressing the methotrexate and Bactrim drug interaction?

There are a couple of items to consider when addressing this drug interaction. The first thing to think about is altering drug therapy. Changing the methotrexate doesn’t make any sense in this scenario given the relative stability of her current rheumatoid arthritis condition. Finding a different agent for the treatment of the UTI makes a lot of sense and that is what I would consider first.

The other thing to consider is the length of therapy. In the situation above, the length of therapy was not specified. In the event of needing UTI prophylaxis (Bactrim long term), there would be a stronger argument to use an alternative antibiotic compared to a patient who is getting a 3-day treatment with the medication. Folic acid deficiency is not a concern at all from my perspective with short-term use (i.e. less than a week or two).

As far as immunosuppression goes, the longer the length of therapy and the higher the dose, the more concern I have. Ideally, I’d like to see an alternative agent to Bactrim used if one is available to treat the infection. A risk versus benefit discussion of Bactrim compared to other agents should be conducted in this scenario.

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