sulfamethoxazole + trimethoprim: clinical use

Prescribing considerations

• Reserve for susceptible infections where the combination's benefit outweighs its risks and, for the listed routine bacterial infections, where there is good reason to prefer it to a single agent.
• Assess renal and hepatic function, concurrent medicines, folate status, potassium risk and previous sulfonamide or trimethoprim reactions.
• Exercise particular caution in older people, G6PD deficiency, serious haematological disease, severe atopy or asthma, and patients at risk of electrolyte disturbance.
• Trimethoprim can inhibit tubular creatinine secretion, causing a modest apparent creatinine rise without an equivalent fall in glomerular filtration.

Contraindications and cautions

• Hypersensitivity to trimethoprim, sulfamethoxazole, sulfonamides, co-trimoxazole or relevant excipients.
• Severe hepatic impairment.
• Severe renal insufficiency when repeated plasma-concentration measurement is unavailable.
• Previous trimethoprim- or sulfonamide-induced immune thrombocytopenia.
• Acute porphyria.
• Infants during the first six weeks of life.
• First trimester of pregnancy.

Monitoring

• Monitor renal function and electrolytes, especially potassium, in patients at risk or receiving interacting medicines.
• For prolonged treatment, folate deficiency or older patients, undertake regular full blood counts; the SmPC advises monthly counts in these groups.
• Monitor liver function and blood counts when clinically indicated, particularly during prolonged or specialist treatment.
• Consider sulfamethoxazole concentrations in significant renal impairment where the product information specifies this capability.

Clinical pharmacology

The components inhibit sequential microbial folate-synthesis steps: sulfamethoxazole inhibits dihydrofolate formation, while trimethoprim inhibits microbial dihydrofolate reductase. Both are principally cleared through the kidneys, and elimination is prolonged by renal impairment.

Formulation and product differences

• Selected oral presentations include tablets and separate adult and paediatric suspensions.
• The tablet scoreline is for easier swallowing, not equal subdivision.
• The adult suspension contains sucrose; the paediatric suspension contains sorbitol. Both contain small amounts of ethanol and formulation-specific excipients.
• The infusion is a concentrate requiring dilution. It contains ethanol, sodium and sodium metabisulphite, which may rarely trigger hypersensitivity or bronchospasm.
• Intravenous treatment is intended when oral treatment is unsuitable or urgent parenteral treatment is needed; it offers no inherent therapeutic advantage over oral treatment.

Oral suspension

Route: Oral

Strengths: 40 mg + 200 mg/5 mL, 80 mg + 400 mg/5 mL

Tablet

Route: Oral

Strengths: 80 mg + 400 mg, 160 mg + 800 mg, 800 mg + 160 mg