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.