Drug reference
Sulfamethoxazole and trimethoprim are used in combination (as co-trimoxazole) because of their synergistic activity (the importance of the sulfonamides has decreased as a result of increasing bacterial resistance and their replacement by antibacterials which are generally more active and less toxic).
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Treatment of susceptible infections ▶BY MOUTH ▶Child 6 weeks–5 months: 120 mg twice daily, alternatively 24 mg/kg twice daily ▶Child 6 months–5 years: 240 mg twice daily, alternatively 24 mg/kg twice daily ▶Child 6–11 years: 480 mg twice daily, alternatively 24 mg/kg twice daily ▶Child 12–17 years: 960 mg twice daily ▶Adult: 960 mg twice daily ▶BY INTRAVENOUS INFUSION ▶Adult: 960 mg every 12 hours, increased to 1.44 g every 12 hours, increased dose used in severe infection Moderate diabetic foot infection | Severe diabetic foot infection ▶BY MOUTH ▶Adult: 960 mg twice daily ▶BY INTRAVENOUS INFUSION ▶Adult: 960 mg every 12 hours, increased if necessary to 1.44 g every 12 hours Leg ulcer infection ▶BY MOUTH ▶Adult: 960 mg twice daily for 7 days ▶BY INTRAVENOUS INFUSION ▶Adult: 960 mg every 12 hours, increased to 1.44 g every 12 hours, increased dose used in severe infection Hospital-acquired pneumonia ▶BY MOUTH ▶Adult: 960 mg twice daily for 5 days then review Acute exacerbation of chronic obstructive pulmonary disease ▶BY MOUTH ▶Adult: 960 mg twice daily for 5 days ▶BY INTRAVENOUS INFUSION ▶Adult: 960 mg every 12 hours, increased if necessary to 1.44 g every 12 hours, increased dose used in severe infection Treatment of Pneumocystis jirovecii (Pneumocystis carinii) infections (undertaken where facilities for appropriate monitoring available—consult microbiologist and product literature) ▶BY MOUTH, OR BY INTRAVENOUS INFUSION ▶Child: 120 mg/kg daily in 2–4 divided doses for 14–21 days, oral route preferred for children ▶Adult: 120 mg/kg daily in 2–4 divided doses for 14–21 days Prophylaxis of Pneumocystis jirovecii (Pneumocystis carinii) infections ▶BY MOUTH ▶Child: 450 mg/m2 twice daily (max. per dose 960 mg twice daily) for 3 days of the week (either consecutively or on alternate days), dose regimens may vary, consult local guidelines ▶Adult: 960 mg once daily, reduced if not tolerated to 480 mg once daily, alternatively 960 mg once daily on alternate days, alternate day dose to be given 3 times weekly, alternatively 960 mg twice a day on alternate days, alternate day dose to be given 3 times weekly Acute prostatitis (initiated under specialist supervision) ▶BY MOUTH ▶Adult: 960 mg twice daily for 14 or 28 days based on clinical assessment DOSE EQUIVALENCE AND CONVERSION ▶480 mg of co-trimoxazole consists of sulfamethoxazole 400 mg and trimethoprim 80 mg. l UNLICENSED USE Co-trimoxazole may be used as detailed below, although these situations are considered unlicensed: . treatment of Burkholderia cepacia infections in cystic fibrosis . treatment of Stenotrophomonas maltophilia infections . g treatment of hospital-acquired pneumonia . treatment of moderate diabetic foot infection . treatment of severe diabetic foot infection . treatment of leg ulcer infection h ▶In children Not licensed for use in children under 6 weeks.
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Acute porphyrias p. 1120
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Asthma. avoid in blood disorders (unless under specialist supervision). avoid in infants under 6 weeks (except for treatment or prophylaxis of pneumocystis pneumonia) because of the risk of kernicterus. elderly (increased risk of serious side-effects). G6PD deficiency (risk of haemolytic anaemia). maintain adequate fluid intake. predisposition to folate deficiency. predisposition to hyperkalaemia
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Co- trimoxazole is a mixture of trimethoprim and sulfamethoxazole (sulphamethoxazole) in the proportions of 1 part to 5 parts. For choice of antibacterial therapy, see Diabetic foot infections, antibacterial therapy p. 533, Pneumocystis pneumonia p. 637, Respiratory system infections, antibacterial therapy p. 538, Skin infections, antibacterial therapy p. 540, Urinary-tract infections p. 622.
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RESTRICTIONS ON THE USE OF CO-TRIMOXAZOLE Co-trimoxazole is the drug of choice in the prophylaxis and treatment of Pneumocystis jirovecii (Pneumocystis carinii) pneumonia; it is also indicated for nocardiasis, Stenotrophomonas maltophilia infection [unlicensed indication], and toxoplasmosis. It should only be considered for use in acute exacerbations of chronic bronchitis and infections of the urinary tract when there is bacteriological evidence of sensitivity to co- trimoxazole and good reason to prefer this combination to a single antibacterial; similarly it should only be used in acute otitis media in children when there is good reason to prefer it. Co-trimoxazole is also used for the treatment of infections caused by Burkholderia cepacia in cystic fibrosis [unlicensed indication].
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→Appendix 1: sulfonamides. trimethoprim
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▶Common or very common Diarrhoea. electrolyte imbalance . fungal overgrowth. headache. nausea. skin reactions ▶Uncommon Vomiting ▶Rare or very rare Agranulocytosis. angioedema. aplastic anaemia. appetite decreased. arthralgia. ataxia. cough. depression. dizziness. dyspnoea. eosinophilia. fever. haemolysis. haemolytic anaemia. hallucination. hepatic disorders. hypoglycaemia. leucopenia. lung infiltration. megaloblastic anaemia. meningitis aseptic. metabolic acidosis. methaemoglobinaemia. myalgia. myocarditis allergic. nephritis tubulointerstitial. neutropenia. oral Infection disorders. pancreatitis. peripheral neuritis. photosensitivity reaction. pseudomembranous enterocolitis. renal impairment. renal tubular acidosis. seizure. serum sickness. severe cutaneous adverse reactions (SCARs). systemic lupus erythematosus (SLE). thrombocytopenia. tinnitus. uveitis. vasculitis. vertigo SIDE-EFFECTS, FURTHER INFORMATION Co-trimoxazole is associated with rare but serious side effects. Discontinue immediately if blood disorders (including leucopenia, thrombocytopenia, megaloblastic anaemia, eosinophilia) or rash (including Stevens-Johnson syndrome or toxic epidermal necrolysis) develop.
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Teratogenic risk in first trimester (trimethoprim a folate antagonist). Neonatal haemolysis and methaemoglobinaemia in third trimester; fear of increased risk of kernicterus in neonates appears to be unfounded.
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Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants (due to sulfamethoxazole).
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Manufacturer advises avoid in severe liver disease.
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▶In adults Avoid if eGFR less than 15 mL/minute/1.73 m2 and if plasma-sulfamethoxazole concentration cannot be monitored. ▶In children Avoid if estimated glomerular filtration rate less than 15 mL/minute/1.73 m2 and if plasma- sulfamethoxazole concentration cannot be monitored. Dose adjustments ▶In adults Use half normal dose if eGFR 15–30 mL/minute/1.73 m2. ▶In children Use half normal dose if estimated glomerular filtration rate 15–30 mL/minute/1.73 m2.
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▶Monitor blood counts on prolonged treatment. ▶In children Plasma concentration monitoring may be required with high doses; seek expert advice.
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▶With intravenous use in children For intermittent intravenous infusion, may be further diluted in glucose 5% and 10% or sodium chloride 0.9%. Dilute contents of 1 ampoule (5 mL) to 125 mL, 2 ampoules (10 mL) to 250 mL or 3 ampoules (15 mL) to 500 mL; suggested duration of infusion 60–90 minutes (but may be adjusted according to fluid requirements); if fluid restriction necessary, 1 ampoule (5 mL) may be diluted with 75 mL glucose 5% and the required dose infused over max. 60 minutes; check container for haze or precipitant during administration. In severe fluid restriction may be given undiluted via a central venous line. ▶With intravenous use in adults For intravenous infusion (Septrin ® for infusion), give intermittently in Glucose 5% or 10% or Sodium chloride 0.9%. Dilute contents of 1 ampoule (5 mL) to 125 mL, 2 ampoules (10 mL) to 250 mL or 3 ampoules (15 mL) to 500 mL; suggested duration of infusion 60–90 minutes (but may be adjusted according to fluid requirements); if fluid restriction necessary, 1 ampoule (5 mL) may be diluted with 75 mL glucose 5% and infused over max. 60 minutes.
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There can be variation in the licensing of Infection different medicines containing the same drug. Solution for infusion EXCIPIENTS: May contain Alcohol, propylene glycol, sulfites ELECTROLYTES: May contain Sodium ▶Co-trimoxazole (Non-proprietary) Trimethoprim 16 mg per 1 ml, Sulfamethoxazole 80 mg per 1 ml Co-trimoxazole 80mg/400mg/5ml solution for infusion ampoules | 10 ampoule P £47.15 DT = £47.15 Oral suspension CAUTIONARY AND ADVISORY LABELS 9 ▶Co-trimoxazole (Non-proprietary) Trimethoprim 8 mg per 1 ml, Sulfamethoxazole 40 mg per 1 ml Co-trimoxazole 40mg/200mg/5ml oral suspension sugar-free | 100 ml P £9.96 DT = £9.96 Trimethoprim 16 mg per 1 ml, Sulfamethoxazole 80 mg per 1 ml Co-trimoxazole 80mg/400mg/5ml oral suspension | 100 ml P £10.95–£10.96 DT = £10.96 Tablet CAUTIONARY AND ADVISORY LABELS 9 ▶Co-trimoxazole (Non-proprietary) Trimethoprim 80 mg, Sulfamethoxazole 400 mg Co-trimoxazole 80mg/400mg tablets | 28 tablet P £15.50 DT = £1.96 | 100 tablet P £7.00–£10.91 Trimethoprim 160 mg, Sulfamethoxazole 800 mg Co-trimoxazole 160mg/800mg tablets | 100 tablet P £23.48 DT = £23.48
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120 mg twice daily,
First-line fragment. Read the complete Indications and Dose section above.
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240 mg twice daily, alternatively
First-line fragment. Read the complete Indications and Dose section above.
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480 mg twice daily, alternatively
First-line fragment. Read the complete Indications and Dose section above.
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960 mg twice daily
First-line fragment. Read the complete Indications and Dose section above.
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120 mg/kg daily in 2–4 divided doses for
First-line fragment. Read the complete Indications and Dose section above.
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450 mg/m2 twice daily (max. per dose 960 mg
First-line fragment. Read the complete Indications and Dose section above.
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