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Trimethoprim + sulfamethoxazole Pregnancy: Trimethoprim is contraindicated during the first trimester of pregnancy (see section 4.3). Studies in animals have shown a teratogenic effect. Epidemiological studies have shown an increased risk of spontaneous abortion and congenital malformations, in particular neural tube defects, oral clefts and cardiovascular defects, in children of mothers treated with trimethoprim during the first trimester of pregnancy. The presumed mechanism of action is thought to be interference with folates. In the second and third trimesters, use should be avoided, unless clinically necessary. Trimethoprim and sulfamethoxazole cross the placenta and their safety in pregnant women has not been established. Case-control studies have shown that there may be an association between exposure to folate antagonists and birth defects in humans. Trimethoprim is a folate antagonist and, in animal studies, both agents have been shown to cause foetal abnormalities (see section 5.3). Folate supplementation should be considered if Co-Trimoxazole is used in pregnancy. Sulfamethoxazole competes with bilirubin for binding to plasma albumin. As significantly maternally derived drug levels persist for several days in the newborn, there may be a risk of precipitating or exacerbating neonatal hyperbilirubinaemia, with an associated theoretical risk of kernicterus, when Co-Trimoxazole is administered to the mother near the time of delivery. This theoretical risk is particularly relevant in infants at increased risk of hyperbilirubinaemia, such as those who are preterm and those with glucose-6-phosphate dehydrogenase deficiency. Breast-feeding: The components of Co-Trimoxazole (trimethoprim and sulfamethoxazole) are excreted in breast milk. Administration of Co-Trimoxazole should be avoided in late pregnancy and in lactating mothers where the mother or infant has, or is at particular risk of developing, hyperbilirubinaemia. Additionally, administration of Co-Trimoxazole should be avoided in infants younger than eight weeks in view of the predisposition of young infants to hyperbilirubinaemia.

Co-trimoxazole

Brand names: Septrin

Co-trimoxazole is a fixed combination of trimethoprim and sulfamethoxazole, used principally for the treatment and prevention of Pneumocystis jirovecii pneumonia and for selected other infections where it is the agent of choice.

Adult dose

Dose: Adults and children over 12 years, by mouth. Dose is expressed in the label's adult "tablet" = 80 mg trimethoprim + 400 mg sulfamethoxazole. Standard dosage for acute infections: 2 tablets every 12 hours. Pneumocystis jirovecii pneumonitis (PJP) treatment: 20 mg/kg/day trimethoprim and 100 mg/kg/day sulfamethoxazole (per kg body weight per day) in two or more divided doses for two weeks. PJP prevention (any one of these schedules): 160 mg trimethoprim/800 mg sulfamethoxazole daily 7 days per week; or 160 mg/800 mg three times per week on alternate days; or 320 mg/1600 mg per day in two divided doses three times per week on alternate days. Nocardiosis and toxoplasmosis: the label states there is no consensus on dosage (see notes).
Route: Oral (tablets, 80 mg trimethoprim/400 mg sulfamethoxazole)
Frequency: Standard dosage: every 12 hours. PJP treatment: two or more divided doses per day for two weeks. PJP prevention: daily, or three times per week on alternate days (see dose).
The pinned product 'Co-Trimoxazole 80 mg/400 mg Tablets' §4.1 covers treatment and prevention of PJP, toxoplasmosis, nocardiosis, and (where bacterial sensitivity is shown) acute uncomplicated urinary tract infection, acute otitis media and acute exacerbation of chronic bronchitis, in adults and children over 12 years. ROUTE: this card covers the ORAL tablet only. The page's intravenous route is NOT covered by this product and no IV dose is written. DURATION (standard dosage): "Treatment should be continued until the patient has been symptom free for two days; the majority will require treatment for at least 5 days." "If clinical improvement is not evident after 7 days therapy, the patient should be reassessed." Acute uncomplicated lower urinary tract infection: "short-term therapy of 1 to 3 days duration has been shown to be effective" as an alternative to the standard dosage. NO MAXIMUM DOSE is written: the only ceiling in §4.2 ("The total daily dose should not exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole") is printed in the PJP-prevention paragraph after the children's sentences and does not say whom it applies to, so it is not carried as an adult maxDose. NOCARDIOSIS (label): "There is no consensus on the most appropriate dosage." "Adult doses of 6 to 8 tablets daily for up to 3 months have been used." TOXOPLASMOSIS (label): "There is no consensus on the most appropriate dosage for the treatment or prophylaxis of this condition." "For prophylaxis, however, the dosages suggested for prevention of Pneumocystis jirovecii pneumonitis may be appropriate." Neither is published as a recommended dose. PAEDIATRIC: this tablet product's §4.1 covers adults and children over 12 years only, who take the adult doses above; paedDose is null (the label's per-kg 'standard dosage for children' is not carried: it is not the PJP dose, and a single calculable figure would understate PJP treatment). Use a children's formulary for children aged 12 years or under. ELDERLY: "Unless otherwise specified standard dosage applies"; §4.4 advises particular care. Some sections of the product information we used were incomplete — check the full SPC. Pregnancy: contraindicated in the first trimester (§4.3, §4.6).

Dose adjustments

Renal

SPC §4.2, impaired renal function, adults and children over 12 years, by creatinine clearance (ml/min): >30 — 2 tablets every 12 hours; 15 to 30 — 1 tablet every 12 hours; <15 — "Not recommended". "No information is available for children aged 12 years and under with renal failure." "Measurements of plasma concentration of sulfamethoxazole at intervals of 2 to 3 days are recommended in samples obtained 12 hours after administration of Co-Trimoxazole. If the concentration of total sulfamethoxazole exceeds 150 microgram/ml then treatment should be interrupted until the value falls below 120 microgram/ml." §4.3: "Contra-indicated in severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed." §4.4: "An adequate urinary output should be maintained at all times."

Hepatic

§4.2: "No data are available relating to dosage in patients with impaired hepatic function." §4.3: "Co-Trimoxazole should not be given to patients with severe impairment of liver function."

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance(s) sulphonamides, trimethoprim, co-trimoxazole or to any of the excipients listed in section 6.1 (§4.3).
  • Severe impairment of liver function (§4.3).
  • Severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed (§4.3).
  • Infants during the first 6 weeks of life (§4.3).
  • History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides (§4.3).
  • Acute porphyria (§4.3).
  • First trimester of pregnancy (§4.3, §4.6).
  • Previous SJS, TEN or DRESS with co-trimoxazole: "the treatment must not be re-started in this patient at any time"; AGEP "contraindicates any new administration of Co-Trimoxazole alone or in combination with other drugs" (§4.4 warnings, not listed in §4.3).

Side effects

  • Very common: hyperkalaemia (§4.8).
  • Common: fungal overgrowth; headache; nausea, diarrhoea; rash. Uncommon: vomiting (§4.8).
  • Very rare: pseudomembranous colitis (§4.8).
  • Blood (very rare): leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anaemia, aplastic anaemia, haemolytic anaemia, methaemoglobinaemia, eosinophilia, purpura, haemolysis in susceptible G-6-PD deficient patients (§4.8).
  • Immune (very rare): serum sickness, anaphylactic reaction, allergic myocarditis, hypersensitivity vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus; severe hypersensitivity reactions associated with PJP (rash, pyrexia, neutropenia, thrombocytopenia, hepatic enzyme increased, hyperkalaemia, hyponatraemia, rhabdomyolysis) (§4.8).
  • Metabolic (very rare): hypoglycaemia, hyponatraemia, decreased appetite, metabolic acidosis (§4.8).
  • Psychiatric: depression, hallucination (very rare); psychotic disorder (not known) (§4.8).
  • Nervous system and sensory (very rare): aseptic meningitis, convulsions, peripheral neuropathy, ataxia, dizziness; vertigo, tinnitus; uveitis. Circulatory shock (not known) (§4.8).
  • Respiratory (very rare): cough, dyspnoea, lung infiltration; severe respiratory toxicity sometimes progressing to ARDS (§4.4).
  • Gastrointestinal (very rare): glossitis, stomatitis, pancreatitis (§4.8).
  • Hepatobiliary (very rare): transaminases increased, blood bilirubin increased, cholestatic jaundice, hepatic necrosis (§4.8).
  • Skin (very rare): photosensitivity reaction, angioedema, exfoliative dermatitis, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis (AGEP); (not known) Sweet's syndrome, DRESS (§4.8).
  • Haemophagocytic lymphohistiocytosis (very rare) (§4.4).
  • Fatalities, although very rare, have occurred from Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract (§4.4).
  • §4.8 is truncated at the source-fetch limit (musculoskeletal and later system-organ classes not retrieved).

Interactions

  • Folinic acid supplementation may be considered during treatment but "should be initiated with caution due to possible interference with antimicrobial efficacy" (§4.4; the full §4.5 interaction section was not retrieved).
  • Elderly patients are more likely to suffer serious effects when there is concomitant use of other drugs together with impaired kidney and/or liver function (§4.4).
  • Cytotoxic therapy: co-trimoxazole has been given to patients receiving it with "little or no additional effect on the bone marrow or peripheral blood" (§4.4).

Monitoring

  • Regular monthly blood counts when given for long periods, or to folate-deficient patients or the elderly (§4.4).
  • Plasma sulfamethoxazole every 2 to 3 days (sample 12 hours after dose) in impaired renal function; interrupt if total sulfamethoxazole exceeds 150 microgram/ml until it falls below 120 microgram/ml (§4.2).
  • PJP treatment: aim for peak plasma or serum trimethoprim of greater than or equal to 5 microgram/ml (§4.2).
  • Serum potassium: close monitoring in patients at risk of hyperkalaemia and hyponatraemia (§4.4).
  • Skin reactions: monitor closely; the highest risk of SJS or TEN is within the first weeks of treatment; discontinue if signs of SJS, TEN or DRESS appear (§4.4).
  • Metabolic acidosis: close monitoring when suspected (§4.4).
  • Maintain adequate urinary output at all times (§4.4).
  • If clinical improvement is not evident after 7 days of therapy, reassess the patient (§4.2).

Clinical monograph

How it works

The two components block sequential steps of bacterial folate synthesis — sulfamethoxazole inhibits dihydropteroate synthase and trimethoprim inhibits dihydrofolate reductase — giving a synergistic effect.

Prescribing in practice

  • It can cause life-threatening reactions including severe cutaneous reactions such as Stevens-Johnson syndrome, blood dyscrasias and hyperkalaemia, so use is restricted to specific indications.
  • It raises the risk of hyperkalaemia, particularly with renal impairment or alongside ACE inhibitors, angiotensin receptor blockers or potassium-sparing diuretics.
  • It potentiates warfarin and methotrexate and should be avoided with methotrexate because of additive antifolate marrow toxicity.

Monitoring

Monitor full blood count, renal function and serum potassium during prolonged or high-dose therapy.

Counselling the patient

  • Report any rash, mouth ulcers, sore throat, fever or unusual bruising immediately.
  • Maintain a good fluid intake during treatment.

Evidence & guidelines

MHRA guidance restricts co-trimoxazole to indications where benefit outweighs the risk of serious skin, blood and electrolyte reactions.

Reference: CSM advice; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Pathways