Potentially Fatal Interaction!
Avoid combining TMP-SMX (Septrin) with even low-dose Methotrexate.
The combo increases MTX exposure (reduced clearance + higher free fraction) and adds antifolate toxicity → real risk of pancytopenia, mucositis, and AKI.
Use only if unavoidable, with minimal duration and critical monitoring.
Evidence level (GRADE): Moderate certainty, (based on consistent case series + pharmacologic data, limited RCT evidence).
