Beschreibung
Trimethoprim and methotrexate both inhibit dihydrofolate reductase (DHFR), producing additive antifolate toxicity with potentially life-threatening pancytopenia and mucositis.
Mechanismus
Trimethoprim inhibits bacterial DHFR but also has measurable affinity for human DHFR; combined with methotrexate's DHFR inhibition and shared renal OCT2/OAT elimination pathways, both pharmacodynamic and pharmacokinetic synergism contribute to toxicity.
Klinische Bedeutung
Multiple case reports and cohort studies document severe pancytopenia, megaloblastic anaemia, and fatal outcomes when trimethoprim is added to methotrexate therapy.
Maßnahmen
Avoid the combination whenever possible, especially with high-dose or weekly low-dose methotrexate regimens; if unavoidable, closely monitor CBC, renal function, and provide folinic acid rescue.
Medizinischer Haftungsausschluss
This content is for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making medication decisions.