Trimethoprim (as
in Bactrim, Septra, Septrin etc)
Adverse effects
and treatment
Trimethoprim is
reasonably well tolerated in general,
and the most frequent adverse effects
at usual doses are pruritis and skin
rash (in about 3 to 7% of patients)
and mild gastrointestinal
disturbances including nausea,
vomiting, and sore mouth.
Rarely, more severe
effects have been reported.
Sulfonamide-like skin reactions,
including exfoliative dermatitis,
erythema multiforme, Stevens-Johnson
syndrome, and toxic epidermal
necrolysis have occurred.
Disturbances of liver enzyme values
and cholestatic jaundice have been
associated with trimethoprim. Rises
in serum creatinine and blood-urea
nitrogen have been reported although
it is unclear whether this represents
genuine renal dysfunction or
inhibition of tubular secretion of
creatinine. Photosensitivity has been
reported. Fever is not uncommon but
occasionally hypersensitivity
reactions may be severe and manifest
as anaphylaxis. Cases of aseptic
meningitis have also been reported.
Trimethoprim
may cause a depression of
haematopoiesis due to interference of
the drug in the metabolism of folic
acid, particularly when given over a
prolonged period or in high doses.
This may manifest as megaloblastic
anaemia, or as thrombocytopenia and
leucopenia; methaemoglobinaemia has
also been seen. Calcium folinate 5 to
15mg daily by mouth may be given to
counter this effect. Trimethoprim
is teratogenic in animals.
Hyperkalaemia. Trimethoprim
has been reported to induce
hyperkalaemia , particularly in
HIV-infected patients being treated
for Pneumocystis carinii
pneumonia or in the elderly. The
hyperkalaemia may be due to
amiloride-like potassium-sparing
properties of trimethoprim,
and may be potentiated by ACE
inhibitors.
Precautions
Trimethoprim
should not be given to patients with
a history of hypersensitivity to the
drug, and it should be discontinued
if a skin rash appears. Care is
necessary in administering trimethoprim
to patients with impaired renal
function to avoid accumulation and
toxicity: it should not be given in
severe renal impairment unless blood
concentrations can be monitored. It
should be used with caution in
patients with severe hepatic damage
as changes may occur in the
absorption and metabolism of trimethoprim.
It is suggested that
regular haematological examination
should be made during prolonged
courses of treatment;
trimethoprim should not usually
be given to patients with serious
haematological disorders and
particularly not in megaloblastic
anaemia secondary to folate
depletion. Caution should be taken in
patients with actual, or possible,
folate deficiency and administration
of folinic acid should be considered.
Trimethoprim should be
avoided during pregnancy.
Trimethoprim appears in breast
milt and care is required when it is
used in breast-feeding mothers.
Elderly patients may be more
susceptible to adverse effects and a
lower dosage may be advisable.
Trimethoprim
may interfere with some diagnostic
tests, including serum-methotrexate
assay where dihydrofolate reductase
is used and the Jaffe reaction for
creatinine.