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Sulphonamide + Folate Synthesis Inhibitor Combination Pregnancy: Verbatim (section 4.6): '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... Folate supplementation should be considered if Co-Trimoxazole for Infusion 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 for Infusion is administered to the mother near the time of delivery.' This summary may be incomplete — check the full SPC.

Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

Brand names: Septrin

Used in: Urinary Tract Infection

Co-trimoxazole (trimethoprim with sulfamethoxazole) is used for specific infections, notably Pneumocystis jirovecii pneumonia (treatment and prophylaxis), and for some urinary, respiratory and other infections.

Adult dose

Dose: 2 ampoules (10 mL) of Co-Trimoxazole 16 mg/80 mg per mL for Infusion - i.e. trimethoprim 16 mg + sulfamethoxazole 80 mg per mL, 10 mL per dose
Route: Intravenous infusion only, after dilution. Verbatim (section 4.2): 'Co-Trimoxazole for Infusion is for administration only by the intravenous route and must be diluted before administration.' The page also lists an oral route - the bundle contains no oral SPC, so no oral dose is given here.
Frequency: Every 12 hours (adults and children over 12 years) - standard dosage for acute infections
SCOPE: intravenous co-trimoxazole only; the indication is the SPC's own 'Standard dosage recommendations for acute infections', plus the Pneumocystis jirovecii regimens quoted below, which are the page's stated primary uses. || VERBATIM (section 4.2): 'Adults and children over 12 years: STANDARD DOSAGE: 2 ampoules (10 ml) every 12 hours'. The count is publishable because the product name pins the strength - 'Co-Trimoxazole 16 mg/80 mg per ml for Infusion' - so both components of this fixed combination are quantified: trimethoprim 16 mg and sulfamethoxazole 80 mg in every mL, 10 mL per dose. One ampoule is 5 mL. || SEVERE INFECTION, verbatim: 'For severe infections in all age groups, dosage may be increased by 50%.' This is a permitted increase, not a labelled ceiling, so maxDose is left blank - no explicit maximum dose appears anywhere in this SPC. || DURATION, verbatim: 'Treatment should be continued until the patient has been symptom free for two days; the majority will require treatment for at least 5 days.' || PNEUMOCYSTIS JIROVECII PNEUMONITIS - TREATMENT, verbatim: '15-20 mg trimethoprim and 75-100 mg sulfamethoxazole per kg of bodyweight per day in two or more divided doses. Therapy should be changed to the oral route as soon as possible and continued for a total treatment period of two weeks. The aim is to obtain peak plasma or serum levels of trimethoprim of greater than or equal to 5 microgram/ml (verified in patients receiving 1-hour infusions of intravenous Co-Trimoxazole).' || PNEUMOCYSTIS PREVENTION, verbatim: 'Standard dosage as described under acute infections for the duration of the period at risk.' || NOCARDIOSIS, verbatim: '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 (one tablet contains 400 mg sulfamethoxazole and 80 mg trimethoprim).' (Tablet strength pinned by the SPC itself.) || TOXOPLASMOSIS, verbatim: 'There is no consensus on the most appropriate dosage for the treatment or prophylaxis of this condition. The decision should be based on clinical experience. For prophylaxis, however, the dosages suggested for prevention of Pneumocystis jirovecii pneumonitis may be appropriate.' || ROUTE CHOICE, verbatim: 'It is intended that Co-Trimoxazole for Infusion should be used only during such a period as the patient is unable to accept oral therapy, where initiation of treatment is particularly urgent or for convenience if the patient is already receiving intravenous fluids. Although Co-Trimoxazole for Infusion is useful in critically ill patients, there may be no therapeutic advantage over the oral preparation.'

Paediatric dose

Dose: 6 mg/kg/day (trimethoprim component)
Route: Intravenous infusion, after dilution
Frequency: Given in two equally divided doses (every 12 hours)
VERBATIM (section 4.2): 'Children aged 12 years and under: The standard dosage for children is equivalent to approximately 6 mg trimethoprim and 30 mg sulfamethoxazole per kg body weight per day, given in two equally divided doses.' || DAILY TOTAL, NOT A SINGLE DOSE: dosePerKg is 6 mg/kg/DAY of trimethoprim. Halve the calculated daily amount for each 12-hourly dose. || FIXED COMBINATION - BOTH COMPONENTS: the same regimen delivers sulfamethoxazole 30 mg/kg/day, which must not be omitted when prescribing. dosePerKg carries the trimethoprim component only because the field takes a single number. || AGE-BANDED VOLUMES given in the SPC alongside the per-kg rule, verbatim: '6 weeks to 5 months 1.25 ml every 12 hours. 6 months to 5 years 2.5 ml every 12 hours. 6 to 12 years 5.0 ml every 12 hours.' These are age bands, not weight bands. || CONCENTRATION DELIBERATELY NULL. The product is 16 mg trimethoprim and 80 mg sulfamethoxazole per mL, but because dosePerKg above is a DAILY total, any volume the calculator derived would be a daily volume and could be mistaken for a single dose. The strength is recorded here in words instead: 16 mg trimethoprim + 80 mg sulfamethoxazole per mL; one ampoule is 5 mL. || AGE LIMIT, verbatim (section 4.3): co-trimoxazole 'should not be given to infants during the first 6 weeks of life'. || SEVERE INFECTION, verbatim: 'For severe infections in all age groups, dosage may be increased by 50%.' || PNEUMOCYSTIS TREATMENT in children uses the same per-kg regimen as adults, verbatim: '15-20 mg trimethoprim and 75-100 mg sulfamethoxazole per kg of bodyweight per day in two or more divided doses.' || RENAL, verbatim: 'No information available for children aged 12 years and under with renal failure.' || Paediatric safety: verify this dose against a children's formulary before prescribing.

Dose adjustments

Renal

Verbatim (section 4.2, adults and children over 12 years): 'Creatinine Clearance (ml/min) Recommended Dosage. > than 30: 2 ampoules (10 ml) every 12 hours. 15-30: 1 ampoule (5 ml) every 12 hours. < 15: Not recommended.' Verbatim: 'No information available for children aged 12 years and under with renal failure.' Section 4.3 also contraindicates the product 'in severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed.'

Hepatic

Verbatim (section 4.2): 'Impaired hepatic function: No data are available relating to dosage in patients with impaired hepatic function.' and 'Caution should be exercised when treating patients with severe hepatic impairment as there may be changes in the absorption and biotransformation of trimethoprim and sulfamethoxazole.' Section 4.3 contraindicates the product 'in patients with severe impairment of liver function'. No numeric dose reduction is given.

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.

Paediatric weight-based calculator

VERBATIM (section 4.2): 'Children aged 12 years and under: The standard dosage for children is equivalent to approximately 6 mg trimethoprim and 30 mg sulfamethoxazole per kg body weight per day, given in two equally divided doses.' || DAILY TOTAL, NOT A SINGLE DOSE: dosePerKg is 6 mg/kg/DAY of trimethoprim. Halve the calculated daily amount for each 12-hourly dose. || FIXED COMBINATION - BOTH COMPONENTS: the same regimen delivers sulfamethoxazole 30 mg/kg/day, which must not be omitted when prescribing. dosePerKg carries the trimethoprim component only because the field takes a single number. || AGE-BANDED VOLUMES given in the SPC alongside the per-kg rule, verbatim: '6 weeks to 5 months 1.25 ml every 12 hours. 6 months to 5 years 2.5 ml every 12 hours. 6 to 12 years 5.0 ml every 12 hours.' These are age bands, not weight bands. || CONCENTRATION DELIBERATELY NULL. The product is 16 mg trimethoprim and 80 mg sulfamethoxazole per mL, but because dosePerKg above is a DAILY total, any volume the calculator derived would be a daily volume and could be mistaken for a single dose. The strength is recorded here in words instead: 16 mg trimethoprim + 80 mg sulfamethoxazole per mL; one ampoule is 5 mL. || AGE LIMIT, verbatim (section 4.3): co-trimoxazole 'should not be given to infants during the first 6 weeks of life'. || SEVERE INFECTION, verbatim: 'For severe infections in all age groups, dosage may be increased by 50%.' || PNEUMOCYSTIS TREATMENT in children uses the same per-kg regimen as adults, verbatim: '15-20 mg trimethoprim and 75-100 mg sulfamethoxazole per kg of bodyweight per day in two or more divided doses.' || RENAL, verbatim: 'No information available for children aged 12 years and under with renal failure.' || Paediatric safety: verify this dose against a children's formulary before prescribing.

Verify in a children's formulary

Contraindications

  • Hypersensitivity to the active substance(s) sulphonamides, trimethoprim, co-trimoxazole or to any of the excipients listed in section 6.1 (section 4.3)
  • Severe impairment of liver function (section 4.3)
  • Severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed (section 4.3)
  • History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides (section 4.3)
  • Acute porphyria (section 4.3)
  • Infants during the first 6 weeks of life (section 4.3)
  • First trimester of pregnancy (section 4.3, see section 4.6)
  • Not a contraindication but an absolute bar on re-exposure (section 4.4): 'If the patient has developed SJS, TEN or DRESS with the use of Co-Trimoxazole, the treatment must not be re-started in this patient at any time.'
  • Not a contraindication but a bar on re-exposure (section 4.4): acute generalised exanthematous pustulosis 'requires cessation of treatment and contraindicates any new administration of Co-Trimoxazole alone or in combination with other drugs.'

Side effects

  • Very common: hyperkalaemia (section 4.8)
  • Common: fungal overgrowth; headache; nausea; diarrhoea; rash
  • Uncommon: vomiting
  • Very rare: pseudomembranous colitis; leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anaemia, aplastic anaemia, haemolytic anaemia, methaemoglobinaemia, eosinophilia, purpura, haemolysis in certain susceptible G-6-PD deficient patients; serum sickness, anaphylactic reaction, allergic myocarditis, hypersensitivity vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus; hypoglycaemia, hyponatraemia, decreased appetite, metabolic acidosis; depression, hallucination; aseptic meningitis, seizure, peripheral neuropathy, ataxia, dizziness; vertigo, tinnitus; uveitis; cough, dyspnoea, lung infiltration; glossitis, stomatitis, pancreatitis; cholestatic jaundice, hepatic necrosis, increased transaminases, increased blood bilirubin; photosensitivity reaction, exfoliative dermatitis, angioedema, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
  • Not known: psychotic disorder; circulatory shock; acute generalised exanthematous pustulosis (AGEP); acute febrile neutrophilic dermatosis (Sweet's syndrome); DRESS
  • Section 4.8: 'Severe hypersensitivity reactions associated with PJP: rash, pyrexia, neutropenia, thrombocytopenia, hepatic enzyme increased, hyperkalaemia, hyponatraemia, rhabdomyolysis.'
  • Section 4.4: 'Fatalities, although very rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract.'
  • Section 4.4: haemophagocytic lymphohistiocytosis (HLH) has been reported very rarely
  • Section 4.4: 'Very rare, severe cases of respiratory toxicity, sometimes progressing to Acute Respiratory Distress Syndrome (ARDS), have been reported during co-trimoxazole treatment.'
  • Section 4.4: 'Fluid overload is possible, especially when very high doses are being administered to patients with underlying cardio-pulmonary disease.'

Monitoring

  • Plasma sulfamethoxazole concentration - section 4.2, verbatim: 'Measurements of plasma concentrations of sulfamethoxazole at intervals of 2 to 3 days are recommended in samples obtained 12 hours after administration... If the concentration of total sulfamethoxazole exceeds 150 micrograms/ml then treatment should be interrupted until the value falls below 120 micrograms/ml.'
  • In Pneumocystis treatment, trimethoprim levels - section 4.2, verbatim: 'The aim is to obtain peak plasma or serum levels of trimethoprim of greater than or equal to 5 microgram/ml.'
  • Skin - section 4.4, verbatim: 'Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.'
  • Signs of pathologic immune activation (HLH) - section 4.4: 'Patients who develop early manifestations of pathologic immune activation should be evaluated immediately.'
  • Respiratory status - section 4.4: cough, fever and dyspnoea with radiological pulmonary infiltrates and deteriorating pulmonary function may be preliminary signs of ARDS
  • Fluid balance on high doses in patients with cardio-pulmonary disease (section 4.4, fluid overload)
  • Urinary output - section 4.4 begins 'An adequate urinary output...'
  • Renal function, since dosing changes below CrCl 30 ml/min and the product is not recommended below CrCl 15 ml/min (section 4.2)
  • This list may be incomplete — check the full SPC.

Clinical monograph

How it works

The two components block sequential steps in bacterial folate synthesis, producing a synergistic effect.

Prescribing in practice

  • It carries sulfonamide risks — serious skin reactions (including Stevens-Johnson syndrome) — and can cause hyperkalaemia and bone-marrow suppression.
  • Avoid or use great caution with methotrexate (additive folate antagonism and marrow toxicity) and with other potassium-raising or marrow-suppressing drugs.
  • Reduce the dose in renal impairment and ensure good hydration; it is usually reserved for specific indications.

Monitoring

For longer courses monitor FBC, renal function and potassium, and review for rash.

Counselling the patient

  • Report any rash promptly, or a sore throat or fever.
  • Drink plenty of fluids.
  • Tell your clinician about other medicines, especially methotrexate.

Evidence & guidelines

First-line for Pneumocystis pneumonia treatment and prophylaxis, and used selectively for other infections per local guidance.

Reference: BHIVA HIV Guidelines 2023; NICE NG112 (UTI); NICE HIV Management Guidelines; 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.

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