Section 15 · Monograph
Trimethoprim-sulfamethoxazole
Reviewed Nov 2026FDA label
Bactrim / SeptraSulfonamide / folate-pathway antibiotic
- Forms
- IV: 16mg/mL TMP | Tab: 80/400, 160/800mg | Susp: 40/200mg per 5mL
- Dose
- Toxoplasmosis alternative: TMP 5mg/kg + SMX 25mg/kg every 12h | Listeria or Nocardia: TMP 15-20mg/kg/day divided every 6-12h
- MOA
- Sequential blockade of bacterial folate synthesis
Indications
- Urinary tract infection, Pneumocystis pneumonia, shigellosis and other susceptible infectionsFDA-labeled
Off-Label Uses
- Alternative therapy for cerebral toxoplasmosisOff-label
- Listeria meningitis (penicillin allergy) and Nocardia CNS infectionOff-label
Mechanism of Action
- Sequential blockade of folate synthesis — sulfamethoxazole inhibits dihydropteroate synthase and trimethoprim inhibits dihydrofolate reductase
Full Dosing
Adult / usual
- Toxoplasmosis alternative: trimethoprim 5mg/kg with sulfamethoxazole 25mg/kg PO/IV every 12 hours
- Listeria meningitis alternative: trimethoprim 15-20mg/kg/day IV divided every 6-8 hours
- Nocardia CNS disease: trimethoprim 15mg/kg/day divided every 6-12 hours (often with imipenem)
Renal
- Adjust for CrCl below 30mL/min
Contraindications
- Hypersensitivity to trimethoprim or sulfonamides
- Megaloblastic anemia due to folate deficiency
- Infants under 2 months; marked hepatic damage or severe renal insufficiency when monitoring is unavailable
Drug Interactions
- Warfarin: increased INR
- Phenytoin levels rise
- ACE inhibitors, ARBs, spironolactone: hyperkalemia
- Methotrexate and dofetilide: toxicity
Adverse Effects
- Rash and Stevens-Johnson syndrome
- Hyperkalemia, creatinine elevation
- Cytopenias, hepatitis
- Aseptic meningitis, hypoglycemia
Monitoring Parameters
- Potassium and serum creatinine
- CBC
- Liver function and rash
Pregnancy & Lactation
- Avoid in first trimester (folate antagonism) and near term (kernicterus) unless benefit justifies
- Avoid in nursing infants under 2 months and those with G6PD deficiency