Co-trimoxazole is a combination of sulfamethoxazole and trimethoprim that blocks two sequential steps in bacterial folate synthesis. It is widely used for urinary tract infections, respiratory infections, and PCP prophylaxis.
Also known as: Cotrimoxazol, Bactrim, Septra, Co-trimoxazole
Sulfonamide + anticoagulant: anticoagulant effect potentiated. Dual mechanism: CYP2C9 inhibition + protein binding displacement.
Sulfamethoxazole moderately inhibits CYP2C9 and displaces warfarin from plasma proteins (~99% bound). Trimethoprim contributes little to this interaction. INR increase is usually 1.5-2-fold, significant but rarely catastrophic. Higher risk in the elderly (comorbidities, polypharmacy) and patients with CYP2C9 variant (poor metabolisers). Monitoring: INR 2-3 times/week in the first week, then weekly.
Sulfonamide + anticoagulant: CYP2C9 inhibited + protein displacement. INR 1.5-2-fold.
Sulfamethoxazole moderately inhibits CYP2C9 and displaces warfarin from plasma proteins. Trimethoprim contributes little. INR may increase 1.5-2-fold. Haemorrhage risk, especially in the elderly.
INR, signs of bleeding.
Monitor INR closely (2-3 times/week) during the first week. Consider reducing warfarin dose 10-20%. No routine alteration required.
DailyMed/FDA (NIH/NLM) — approved Bactrim label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62
Sulfonamide + biguanide: risk of hypoglycaemia and lactic acidosis. Trimethoprim may reduce GFR and electrolytes.
The combination presents three risk mechanisms: (1) Hypoglycaemia — trimethoprim may sensitise pancreatic beta cells (partially elucidated mechanism). (2) Hyperkalaemia — trimethoprim blocks renal ENaC channels (similar to amiloride effect). (3) Reduced GFR — dehydration from additive diuretic effect. Particularly elevated risk in: the elderly, baseline eGFR <60, concomitant ACE inhibitor/ARB/potassium-sparing diuretic use. Strategy: monitor blood glucose (twice daily in the first week), potassium (weekly), and creatinine (fortnightly).
Sulfonamide + biguanide: hypoglycaemia, hyperkalaemia, reduced GFR. Monitor.
The combination may cause: (1) hypoglycaemia (mechanism not fully elucidated — possibly beta-cell sensitisation), (2) hyperkalaemia (trimethoprim blocks potassium channels), (3) reduced GFR (dehydration). Higher risk in the elderly and renal impairment.
Blood glucose, potassium, GFR, electrolytes.
Monitor blood glucose, electrolytes, and GFR. Maintain adequate hydration. Consider reducing metformin dose if eGFR <45.
DailyMed/FDA (NIH/NLM) — approved Bactrim label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62
Trimethoprim blocks potassium channels — K+-rich foods may worsen hyperkalaemia.
Avoid excess potassium-rich foods (banana, orange, potato) during prolonged treatment.
Renal excretion — accumulation at eGFR <30. Trimethoprim blocks potassium channels (hyperkalaemia). Sulfamethoxazole precipitates in acidic urine.
eGFR 15-30: 50% dose reduction. eGFR <15: avoid. Alkalinise urine to prevent crystalluria.
DailyMed/FDA (NIH/NLM) — approved Bactrim label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62
CONTRAINDICATED in 3rd trimester (kernicterus). Avoid in 1st trimester (folate). May consider in 2nd trimester for PCP.
3rd trimester: CONTRAINDICATED. 1st trimester: avoid. 2nd trimester: only for serious indications.
Excreted in breast milk. CONTRAINDICATED during breastfeeding.
Effects on fertility in animals. Inadequate human data.
DailyMed/FDA (NIH/NLM) — approved Bactrim label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal (synergistic): blocks two steps in folate synthesis. Sulfamethoxazole inhibits DHPS, trimethoprim inhibits DHFR. Additive/bactericidal effect in combination.
Sulfamethoxazole: structural analogue of PABA — competes with PABA for dihydropteroate synthase. Trimethoprim: selectively inhibits bacterial DHFR (50,000x more potent against bacterial vs. human DHFR).
Sulfamethoxazole: complete oral absorption (~90%), peaks in 1-4 h. Trimethoprim: rapid and complete oral absorption, peaks in 1-4 h.
Sulfamethoxazole: hepatic acetylation (N-acetyltransferase). Trimethoprim: partial hepatic metabolism (CYP2C8). Both renally excreted.
Sulfamethoxazole: 10 h. Trimethoprim: 8-10 h. Combination: synergistic effect maintained throughout the interval.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
