STOP — Contraindicated
FDA-documented contraindication in many contexts. Additive antifolate toxicity. Pancytopenia and death have been reported. Use alternative antibiotics.
Evidence level: STRONG
Methotrexate and Bactrim both block folic acid metabolism in your body. Taking them together can cause a severe, potentially fatal drop in blood cell counts (pancytopenia). This combination has caused deaths.
Both methotrexate and trimethoprim inhibit dihydrofolate reductase (DHFR). Additive antifolate toxicity causes severe pancytopenia. Sulfamethoxazole may also displace methotrexate from plasma proteins and reduce renal clearance. FDA methotrexate label warns.
Do NOT take Bactrim if you are on methotrexate. Tell every doctor and pharmacist that you take methotrexate. There are many alternative antibiotics for most infections.
Follow each medication's specific timing instructions. Trimethoprim-Sulfamethoxazole — check if it requires an empty stomach or should be taken with food. Methotrexate follows its normal schedule. Complete the full antibiotic course as prescribed.
Higher risk for: those with liver or renal impairment, elderly, concurrent use of nephrotoxic or hepatotoxic drugs, history of C. difficile infection, or those on narrow therapeutic index medications (warfarin, digoxin).
Fever, sore throat, mouth sores, unusual bruising or bleeding, extreme fatigue, shortness of breath, pale skin — these indicate dangerously low blood cell counts
Use alternative antibiotics (amoxicillin, cephalosporins, fluoroquinolones depending on indication). If TMP-SMX was given accidentally, check CBC urgently. Ensure folic acid supplementation.
Antibiotic interactions are often temporary (duration of treatment). Space supplements and probiotics 2-3 hours away from antibiotic doses. Ask your pharmacist if timing adjustments can reduce the interaction risk.
Methotrexate and Bactrim both block folic acid metabolism in your body. Taking them together can cause a severe, potentially fatal drop in blood cell counts (pancytopenia). This combination has caused deaths.
Follow each medication's specific timing instructions. Trimethoprim-Sulfamethoxazole — check if it requires an empty stomach or should be taken with food. Methotrexate follows its normal schedule. Complete the full antibiotic course as prescribed.
Fever, sore throat, mouth sores, unusual bruising or bleeding, extreme fatigue, shortness of breath, pale skin — these indicate dangerously low blood cell counts
Antibiotic interactions are often temporary (duration of treatment). Space supplements and probiotics 2-3 hours away from antibiotic doses. Ask your pharmacist if timing adjustments can reduce the interaction risk.
Use alternative antibiotics (amoxicillin, cephalosporins, fluoroquinolones depending on indication). If TMP-SMX was given accidentally, check CBC urgently. Ensure folic acid supplementation.
Or browse the full interaction database (121,000+ pairs).