Sulfamethoxazole (as in
Bactrim, Septra, Septrin etc)
Adverse effects and
treatment
Nausea, vomiting, anorexia, and
diarrhoea are relatively common following the
administration of sulfamethoxazole
and other sulfonamides.
Hypersensitivity reactions to
sulfonamides have proved a problem. Fever is
relatively common, and reactions involving
the skin may include rashes, pruritis,
photosensitivity reactions, exfoliative
dermatitis, and erythema nodosum. Severe,
potentially fatal, skin reactions including
toxic epidermal necrolysis and the
Stevens-Johnson syndrome have occurred in
patients treated with sulfonamides.
Dermatitis may also occur from contact of
sulfonamides with the skin. Systemic lupus
erythematosus, particularly exacerbation of
pre-existing disease, has also been reported.
Nephrotoxic reactions including
interstitial nephritis and tubular necrosis,
which may result in renal failure, have been
attributed to hypersensitivity to sulfamethoxazole.
Lumbar pain, haematuria, oliguria, and anuria
may also occur due to crystallisation in the
urine of sulfamethoxazole or its
less soluble acetylated metabolite. The risk
of crystalluria can be reduced by the
administration of fluids to maintain a high
urine output. If necessary, alkalinisation of
the urine by administration of sodium
bicarbonate may increase solubility and aid
the elimination of sulfonamides.
Blood disorders have
occasionally occurred during treatment with
the sulfonamides including sulfamethoxazole,
and include agranulocytosis, aplastic
anaemia, thrombocytopenia, leucopenia,
hypothrombinaemia, and eosinophilia. Many of
these effects on the blood may result from
hypersensitivity reactions. Sulfonamides may
rarely cause cyanosis due to
methaemoglobinaemia. Acute haemolytic anaemia
is a rare complication which may be
associated with glucose-6-phosphate
dehydrogenase deficiency.
Other adverse effects which may
be manifestations of a generalised
hypersensitivity reaction to sulfonamides
include a syndrome resembling serum sickness,
liver necrosis, hepatomegaly and jaundice,
myocarditis, pulmonary eosinophilia and
fibrosing alveolitis, and vasculitis
including polyarteritis nodosa. Anaphylaxis
has been reported only very rarely.
Other adverse reactions that
have been reported after the administration
of sulfamethoxazole or other
sulfonamides include hypoglycaemia,
hypothyrodism, neurological reactions
including aseptic meningitis, ataxia, benign
intracranial hypertension, convulsions,
dizziness. drowsiness, fatigue, headache,
insomnia, mental depression, peripheral or
optic neuropathies, psychoses, tinnitus,
vertigo, and pancreatitis.
Sulfonamides may displace
serum-bound biluribin, resulting in jaundice
and kernicterus in premature neonates.
As with other antimicrobials, sulfamethoxazole
may cause alterations of the bacterial flora
in the gastrointestinal tract. There is,
therefore, the possibility, although it
appears to be small, that pseudomembranous
colitis may occur.
Slow acetylators of sulfamethoxazole
may be at greater risk of adverse reactions
than fast acetylators.
Precautions
In patients receiving sulfamethoxazole,
adequate fluid intake is necessary to reduce
the risk of crystalluria; the daily urine
output should be 1200 to 1500 mL or more. The
administration of compounds which render the
urine acidic may increase the risk of
crystalluria; the risk may be reduced with
alkaline urine.
Treatment with sulfonamides
should be discontinued immediately a rash
appears because of the danger of severe
allergic reactions such as the
Stevens-Johnson syndrome.
Sulfamethoxazole should
be given with care to patients with renal or
hepatic impairment and is contra-indicated in
patients with severe renal or hepatic failure
or with blood disorders. Dosage reduction may
be necessary in renal impairment. Complete
blood counts and urinalyses with microscopic
examination should be carried out
particularly during prolonged therapy. Sulfamethoxazole
should not be given to patients with a
history of hypersensitivity to sulfonamides
as cross-sensitivity may occur between drugs
of this group. Care is generally advisable in
patients with a history of allergy or asthma.
Caution is also needed in the elderly, who
may be more likely to have other risk factors
for reactions. Some authorities consider sulfamethoxazole
to be contra-indicated in lupus erythematosus
as it may exacerbate the condition. Patients
with glucose 6-phosphate dehydrogenase
deficiency may be at risk of haemolytic
reactions.
Sulfamethoxazole and
other sulfonamides are not usually given to
infants within 1 to 2 months of birth because
of the risk of kernicterus; for the same
reason, they are generally contra-indicated
in women prior to delivery, and in
breast-feeding mothers.
Patients with Aids may be
particularly prone to adverse reactions,
especially when sulfamethoxazole is
given in combination with trimethoprim as
co-trimoxazole.
Sulfonamides have been reported
to interfere with some diagnostic tests,
including those for urea, creatinine, and
urinary glucose and urobilinogen.