This
page is from a campaign
by award-winning investigative journalist Brian Deer in The
Sunday Times of London over
risks and side-effects
from this antibiotic, marketed
under many names, such as Bactrim,
Bactrim DS, Septra, Septra DS,
Septrin, Sulfatrim, SMZ/TMP,
Septran and co-trimoxazole | The investigation | Symptom searcher | Tell Brian & help others
With trimethoprim, sulfamethoxazole
is one of two ingredients in this drug -
and the one considered most responsible
for adverse events. Below is information
on sulfamethoxazole side-effects given by
Martindale, the authoritative reference
work from the Pharmaceutical Society of
Great Britain (33rd edition, April 2002).
You can read personal stories in letters to The Sunday
Times and in emails to this website
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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.
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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.
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| 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.
Pharmaceutical
Society of Great Britain, April 2002.
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