BNF for Children 2011-2012

BNFC 2011–2012 5.1.8 Sulfonamides and trimethoprim 2895.1.8 Sulfonamides andtrimethoprimThe importance of the sulfonamides has decreased as aresult of increasing bacterial resistance and their replacementby antibacterials which are generally moreactive and less toxic.Sulfamethoxazole and trimethoprim are used in combination(as co-trimoxazole) because of their synergisticactivity. However, co-trimoxazole is associated with rarebut serious side-effects e.g. Stevens-Johnson syndromeand blood dyscrasias, notably bone marrow depressionand agranulocytosis (see CSM recommendationsbelow). Co-trimoxazole should be avoided in childrenless than 6 weeks of age (except for treatment andprophylaxis of pneumocystis pneumonia) because ofthe risk of kernicterus. There is a risk of haemolyticanaemia if used in children with glucose-6-phosphatedehydrogenase (G6PD) deficiency (section 9.1.5).Restrictions on the use of co-trimoxazoleCo-trimoxazole should be limited to the role of drugof choice in Pneumocystis jirovecii (Pneumocystiscarinii) pneumonia; it is also indicated for toxoplasmosisand nocardiasis. It should now only beconsidered for use in acute exacerbations of chronicbronchitis and infections of the urinary tract whenthere is good bacteriological evidence of sensitivityto co-trimoxazole and good reason to prefer thiscombination to a single antibacterial; similarly itshould only be used in acute otitis media in childrenwhen there is good reason to prefer it.Trimethoprim can be used alone for urinary- and respiratory-tractinfections and for shigellosis and invasivesalmonella infections. Trimethoprim has side-effectssimilar to co-trimoxazole but they are less severe andoccur less frequently.For topical preparations of sulfonamides used in thetreatment of burns see section 13.10.1.1.CO-TRIMOXAZOLEA mixture of trimethoprim and sulfamethoxazole(sulphamethoxazole) in the proportions of 1 part to 5partsCautions maintain adequate fluid intake; avoid inblood disorders (unless under specialist supervision);monitor blood counts on prolonged treatment; discontinueimmediately if blood disorders or rashdevelop; predisposition to folate deficiency; asthma;G6PD deficiency (section 9.1.5); avoid in infants under6 weeks (except for treatment or prophylaxis ofpneumocystis pneumonia); interactions: Appendix 1(trimethoprim, sulfamethoxazole)Contra-indications acute porphyria (section 9.8.2)Hepatic impairment manufacturer advises avoid insevere liver diseaseRenal impairment use half normal dose if estimatedglomerular filtration rate 15–30 mL/minute/1.73 m 2 ;avoid if estimated glomerular filtration rate less than15 mL/minute/1.73 m 2 and if plasma-sulfamethoxazoleconcentration cannot be monitoredPregnancy teratogenic risk in first trimester (trimethoprima folate antagonist). Neonatal haemolysisand methaemoglobinaemia in third trimester; fear ofincreased risk of kernicterus in neonates appears tobe unfoundedBreast-feeding small risk of kernicterus in jaundicedinfants and of haemolysis in G6PD-deficient infants(due to sulfamethoxazole)Side-effects nausea, diarrhoea; headache, hyperkalaemia;rash (very rarely including Stevens-Johnsonsyndrome, toxic epidermal necrolysis, photosensitivity)—discontinueimmediately; less commonlyvomiting; very rarely glossitis, stomatitis, anorexia,liver damage (including jaundice and hepatic necrosis),pancreatitis, antibiotic-associated colitis, myocarditis,cough and shortness of breath, pulmonaryinfiltrates, aseptic meningitis, depression, convulsions,peripheral neuropathy, ataxia, tinnitus, vertigo, hallucinations,hypoglycaemia, blood disorders (includingleucopenia, thrombocytopenia, megaloblastic anaemia,eosinophilia), hyponatraemia, renal disordersincluding interstitial nephritis, arthralgia, myalgia,vasculitis, systemic lupus erythematosus, and uveitis;rhabdomyolysis reported in HIV-infected patientsPharmacokinetics plasma concentration monitoringmay be required with high doses or during moderateto severe renal impairment; seek expert adviceLicensed use not licensed for use in children under 6weeksIndication and doseTreatment of susceptible infections (but seenotes above) dose expressed as co-trimoxazole. By mouthChild 6 weeks–12 years 24 mg/kg twice dailyorChild 6 weeks–6 months 120 mg twice dailyChild 6 months–6 years 240 mg twice dailyChild 6–12 years 480 mg twice dailyChild 12–18 years 960 mg twice daily. By intravenous infusionChild 6 weeks–18 years 18 mg/kg every 12hours; increased in severe infection to 27 mg/kg(max. 1.44 g) every 12 hoursTreatment of Pneumocystis jirovecii (P. carinii)infections (undertaken where facilities forappropriate monitoring available—consultmicrobiologist and product literature). By mouth or by intravenous infusionChild 1 month–18 years 60 mg/kg every 12hours for 14–21 days; total daily dose may alternativelybe given in 3–4 divided dosesNote oral route preferredProphylaxis of Pneumocystis jirovecii (P. carinii)infections. By mouthChild 1 month–18 years 450 mg/m 2 (max960 mg) twice daily for three days of the week(either consecutively or on alternate days)Note dose regimens may vary, consult local guidelinesNote 480 mg of co-trimoxazole consists of sulfamethoxazole400 mg and trimethoprim 80 mgAdministration for intermittent intravenous infusionmay be further diluted in glucose 5% and 10% orsodium chloride 0.9%. Dilute contents of5 Infections