Folate Synthesis Inhibitor Combination — PCP / Toxoplasma / Nocardia / UTI Prophylaxis Pregnancy: Avoid in 1st trimester (folate antagonism — neural tube defects) and near term (neonatal kernicterus/methaemoglobinaemia); can be used in 2nd trimester with folate supplementation

Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

Brand names: Septrin

Adult dose

Dose: PCP treatment (severe): 120 mg/kg/day IV in 2–4 divided doses × 21 days; PCP prophylaxis (HIV): 960 mg once daily or 3x/week; Toxoplasma prophylaxis: 960 mg once daily; UTI (uncomplicated — increasing resistance): 960 mg BD × 7 days

Route: Oral or IV

Frequency: Twice daily (treatment) or once daily (prophylaxis)

Max: 120 mg/kg/day IV (PCP treatment)

960 mg co-trimoxazole = 160 mg trimethoprim + 800 mg sulfamethoxazole. High-dose PCP treatment: use IV; desensitisation protocols exist for sulfonamide-allergic HIV patients where PCP risk is high. Adjunctive corticosteroids (prednisolone 40 mg BD) indicated if PaO2 <70 mmHg or A-a gradient >35 mmHg in PCP.

Paediatric dose

Dose: PCP treatment: 6 mg/kg TMP component every 6 hours; PCP prophylaxis: 150 mg/m² TMP once daily (3 consecutive days/week) mg/kg

Route: Oral or IV

Frequency: Every 6 hours (treatment); once daily 3x/week (prophylaxis)

Max: Adult dose equivalent

BNFc: used extensively in paediatric HIV, immunocompromised oncology patients; suspension 480 mg/5 mL available (TMP component)

Dose adjustments

Renal

CrCl 15–30: half dose; CrCl <15: avoid (or specialist guidance); sulfonamide metabolites accumulate

Hepatic

Avoid in severe hepatic impairment

Paediatric weight-based calculator

Patient weight (kg)

BNFc: used extensively in paediatric HIV, immunocompromised oncology patients; suspension 480 mg/5 mL available (TMP component)

Clinical pearls

Trimethoprim hyperkalaemia: trimethoprim blocks ENaC sodium channels in distal nephron (same as amiloride) — reduces K+ excretion; high-dose PCP treatment causes clinically significant hyperkalaemia, especially with concurrent RAAS drugs — monitor K+ closely
PCP adjunctive steroids: prednisolone 40 mg BD days 1–5, 20 mg BD days 6–10, 20 mg OD days 11–21 — reduces mortality by ~50% in severe PCP (PaO2 <70 mmHg on room air)
Folinic acid (not folic acid) given concurrently in PCP treatment protects against TMP/SMX-induced bone marrow suppression without reducing anti-PCP efficacy
Desensitisation for sulfonamide allergy in HIV: gradual dose escalation over 2–11 days — achieves tolerance in most patients

Contraindications

Sulfonamide allergy
Megaloblastic anaemia due to folate deficiency
Severe renal or hepatic impairment
Neonates <6 weeks (kernicterus risk from sulfonamide displacing bilirubin)

Side effects

Rash (including Stevens-Johnson syndrome, TEN — sulfonamide class)
GI disturbance
Myelosuppression (especially in folate deficiency — give folinic acid in PCP treatment)
Hyperkalaemia (trimethoprim blocks distal tubular K excretion — especially significant in renal impairment or with other K-sparing drugs)
Nephrotoxicity (crystalluria at high doses)
Haemolytic anaemia (G6PD deficiency)
Photosensitivity

Interactions

Warfarin — enhanced INR (CYP2C9 inhibition)
Methotrexate — increased toxicity (folate pathway competition)
Phenytoin — increased phenytoin toxicity
ACE inhibitors/ARBs/potassium-sparing diuretics — hyperkalaemia (trimethoprim mechanism)
Ciclosporin — nephrotoxicity and increased creatinine (tubular secretion competition)

Monitoring

Renal function and electrolytes (especially potassium — CRITICAL in high-dose treatment)
FBC (myelosuppression)
LFTs
Rash monitoring (SJS/TEN early warning — mucous membrane involvement)
Blood gases (PCP treatment response)

Reference: BNFc; BNF 90; BHIVA HIV Guidelines 2019; NICE NG39 (HIV Testing and Prevention); IDSA PCP Guidelines; MHRA SPC Septrin. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways