co-trimoxazole
sulfonamide antibiotic· Brands: Bactrim, Septra, SeptrinIVPO
Mechanism of action
Co-trimoxazole combines sulfamethoxazole, which inhibits dihydropteroate synthase, and trimethoprim, which inhibits dihydrofolate reductase. This sequential blockade of bacterial folate synthesis prevents synthesis of purines and pyrimidines, and is bactericidal against sensitive organisms.
Pharmacokinetics
The two components have similar elimination half-lives (approximately 8 to 11 hours).
Indications & dosing
Uncomplicated urinary tract infection
Given as co-trimoxazole 160/800 mg; usual course 3 days.
- adult · PO: 160 mg (trimethoprim) twice daily · Given as co-trimoxazole 160/800 mg; usual course 3 days.
Pneumocystis jiroveci pneumonia (PCP) treatment
Combine with sulfamethoxazole 100 mg/kg/day; treat for 21 days.
- adult · PO: 20 mg/kg/day (TMP) every 6 hours · Combine with sulfamethoxazole 100 mg/kg/day; treat for 21 days.
Pneumocystis jiroveci pneumonia (PCP) prophylaxis
Alternative dosing: 160 mg three times weekly.
- adult · PO: 160 mg (trimethoprim) once daily · Alternative dosing: 160 mg three times weekly.
Acute exacerbations of chronic bronchitis
Given as co-trimoxazole 160/800 mg for 5 days; resistance common, check local guidance.
- adult · PO: 160 mg (trimethoprim) twice daily · Given as co-trimoxazole 160/800 mg for 5 days; resistance common, check local guidance.
Shigellosis
Given as co-trimoxazole 160/800 mg for 5 days.
- adult · PO: 160 mg (trimethoprim) twice daily · Given as co-trimoxazole 160/800 mg for 5 days.
Traveler's diarrhoeaoff-label
Off-label in many regions; given as co-trimoxazole 160/800 mg for 3 days.
- adult · PO: 160 mg (trimethoprim) twice daily · Off-label in many regions; given as co-trimoxazole 160/800 mg for 3 days.
Contraindications & precautions
- Hypersensitivity to sulfonamides, trimethoprim, or any component of co-trimoxazole · Includes previous severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or anaphylaxis.
- Severe hepatic damage or severe renal impairment (unless dialysis is available) · Co-trimoxazole is hepatotoxic and can accumulate in renal failure; dose adjustment is not sufficient in severe impairment.
- Blood dyscrasias (e.g., aplastic anaemia, agranulocytosis, thrombocytopenia) · May exacerbate the underlying condition and increase risk of serious haematological toxicity.
- Porphyria · Sulfonamides can precipitate acute porphyric attacks.
- Infants under 6 weeks of age · Risk of kernicterus due to displacement of bilirubin and immature hepatic metabolism.
- Pregnancy at term and breastfeeding of infants under 2 months · Sulfonamides cross the placenta and are excreted in breast milk; risk of kernicterus in the newborn.
- Monitor blood counts, especially in elderly patients or those with pre-existing haematological abnormalities; advise patients to report any signs of infection or bleeding.
- Monitor renal function and serum potassium, particularly in patients with renal impairment, the elderly, or those receiving potassium-sparing agents or ACE inhibitors.
- Ensure adequate fluid intake to prevent crystalluria in patients with impaired renal function or on prolonged high-dose therapy.
- Use with caution in patients with folate deficiency, as co-trimoxazole can precipitate megaloblastic anaemia; consider folinic acid supplementation.
- Avoid in patients with G6PD deficiency, as haemolysis may occur.
- Use with caution in patients with asthma or severe allergies, as sulfonamides may exacerbate bronchospasm.
Adverse effects
- Nausea, vomiting, diarrhoea
- Rash (maculopapular or urticarial)
- Stevens-Johnson syndrome and toxic epidermal necrolysisserious
- Blood dyscrasias: agranulocytosis, aplastic anaemia, thrombocytopenia, haemolytic anaemiaserious
- Hyperkalaemiaserious
- Hepatitis, cholestatic jaundice, hepatocellular necrosisserious
- Crystalluria and acute kidney injuryserious
- Hypersensitivity reactions including anaphylaxis, angioedema, and drug feverserious
Interactions
- methotrexatecontraindicatedCo-prescription is contraindicated. Avoid concurrent use. If absolutely necessary, use alternative antibiotics with no antifolate activity. Monitor full blood count and methotrexate levels frequently if co-administration is unavoidable.
Renal & hepatic adjustment
- eGFR 15–29: Use half the usual dose.
- eGFR 0–14: Avoid use; consider an alternative antibiotic. (avoid)
Monitoring, pregnancy & toxicity
- Full blood count · At baseline and periodically during prolonged therapy
- Serum potassium · At baseline and periodically, especially in elderly or those on potassium-sparing agents
- Renal function (serum creatinine, eGFR) · At baseline and periodically
- Liver function tests · At baseline and if hepatic symptoms develop
- Signs of skin hypersensitivity · Throughout therapy; advise patient to report rash immediately
- Pregnancy: Co-trimoxazole is contraindicated in pregnancy due to folate antagonism, which carries a risk of neural tube defects and other teratogenic effects, and the risk of kernicterus in the neonate. Use only if the potential benefit clearly outweighs the risk and no alternative is available.
- Toxicity: Hypersensitivity reactions including rash, Stevens-Johnson syndrome, and toxic epidermal necrolysis may occur. · Discontinue immediately and consider supportive care; seek urgent dermatological review for severe reactions.
- Toxicity: Bone marrow suppression: leukopenia, thrombocytopenia, and megaloblastic anaemia can occur, especially with high doses or prolonged use. · Discontinue therapy if severe; monitor blood counts and support haematopoiesis with folate if indicated.
- Toxicity: Hyperkalaemia, particularly in patients with renal impairment or taking potassium-sparing drugs. · Monitor serum potassium; discontinue drug and institute standard hyperkalaemia treatment if significant.
- Toxicity: Gastrointestinal upset: nausea, vomiting, and diarrhoea are common. · Symptomatic treatment, ensure hydration, and discontinue if severe.
Clinical notes
Used for urinary tract infections, respiratory tract infections, and as prophylaxis or treatment for Pneumocystis jirovecii pneumonia. Reserve for infections where resistance patterns and other options have been considered. Adverse effects include nausea, rash, and hypersensitivity reactions, and rarely blood dyscrasias. Caution in renal and hepatic impairment, folate deficiency, and pregnancy. Avoid in patients with sulphonamide allergy.
Log in to read the full co-trimoxazole monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary