ANTIBACTERIALS›SULFONAMIDES
Co-trimoxazole
lDRUG ACTIONSulfamethoxazole 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).lINDICATIONS AND DOSE
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
▶BY INTRAVENOUS INFUSION
▶Child 6 weeks–17 years: 18 mg/kg every 12 hours;
increased to 27 mg/kg every 12 hours (max. per dose
1. 44 g), increased dose used in severe infection
Treatment ofPneumocystis 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
Prophylaxis ofPneumocystis jirovecii(Pneumocystis
carinii) infections
▶BY MOUTH
▶Child: 450 mg/m^2 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
DOSE EQUIVALENCE AND CONVERSION
▶ 480 mg of co-trimoxazole consists of sulfamethoxazole
400 mg and trimethoprim 80 mg.lUNLICENSED USENot licensed forBurkholderia cepacia
infections in cysticfibrosis. Not licensed for
Stenotrophomonas maltophiliainfections. Not licensed for
use in children under 6 weeks.IMPORTANT SAFETY INFORMATION
RESTRICTIONS ON THE USE OF CO-TRIMOXAZOLE
Co-trimoxazole is the drug of choice in the prophylaxis
and treatment ofPneumocystis jirovecii(Pneumocystis
carinii) pneumonia; it is also indicated for nocardiasis,
Stenotrophomonas maltophiliainfection [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 byBurkholderia cepaciain
cysticfibrosis [unlicensed indication].lCONTRA-INDICATIONSAcute porphyrias p. 603
lCAUTIONSAsthma.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.G6PD
deficiency (risk of haemolytic anaemia).maintain
adequatefluid intake.predisposition to folate deficiencylINTERACTIONS→Appendix 1 : sulfonamides.trimethoprim
lSIDE-EFFECTS
▶Common or very commonDiarrhoea.electrolyte imbalance
.fungal overgrowth.headache.nausea.skin reactions
▶UncommonVomiting
▶Rare or very rareAgranulocytosis.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
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 INFORMATIONCo-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, toxic
epidermal necrolysis) develop.
lPREGNANCYTeratogenic risk infirst trimester
(trimethoprim a folate antagonist). Neonatal haemolysis
and methaemoglobinaemia in third trimester; fear of
increased risk of kernicterus in neonates appears to be
unfounded.
lBREAST FEEDINGSmall risk of kernicterus in jaundiced
infants and of haemolysis in G 6 PD-deficient infants (due
to sulfamethoxazole).
lHEPATIC IMPAIRMENTManufacturer advises avoid in
severe liver disease.
lRENAL IMPAIRMENTAvoid if estimated glomerular
filtration rate less than 15 mL/minute/ 1. 73 m^2 and if
plasma-sulfamethoxazole concentration cannot be
monitored.
Dose adjustmentsUse half normal dose if estimated
glomerularfiltration rate 15 – 30 mL/minute/ 1. 73 m^2.
MonitoringPlasma concentration monitoring may be
required in patients with moderate to severe renal
impairment; seek expert advice.
lMONITORING REQUIREMENTS
▶Plasma concentration monitoring may be required with
high doses; seek expert advice.
▶Monitor blood counts on prolonged treatment.
lDIRECTIONS FOR ADMINISTRATIONFor 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); iffluid 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
severefluid restriction may be given undiluted via a
central venous line.
lPRESCRIBING AND DISPENSING INFORMATION
Co-trimoxazole is a mixture of trimethoprim and
sulfamethoxazole (sulphamethoxazole) in the proportions
of 1 part to 5 parts.
Flavours of oral liquid formulations may include banana,
or vanilla.350 Bacterial infection BNFC 2018 – 2019
Infection5