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OVERDOSE
Tablets and Suspensions
Acute
The amount of a single dose of sulfamethoxazole; trimethoprim that
is either associated with symptoms of overdosage or is likely to
be life-threatening has not been reported. Signs and symptoms of
overdosage reported with sulfonamides include anorexia, colic, nausea,
vomiting, dizziness, headache, drowsiness, and unconsciousness.
Pyrexia, hematuria, and crystalluria may be noted. Blood dyscrasias
and jaundice are potential late manifestations of overdosage. Signs
of acute overdosage with trimethoprim include nausea, vomiting,
dizziness, headache, mental depression, confusion and bone marrow
depression.
General principles of treatment include the institution of gastric
lavage or emesis; forcing oral fluids; and the administration of
intravenous fluids if urine output is low and renal function is
normal. Acidification of the urine will increase renal elimination
of trimethoprim. The patient should be monitored with blood counts
and appropriate blood chemistries, including electrolytes. If a
significant blood dyscrasia or jaundice occurs, specific therapy
should be instituted for these complications. Peritoneal dialysis
is not effective and hemodialysis is only moderately effective in
eliminating sulfamethoxazole; trimethoprim.
Chronic
Use of sulfamethoxazole; trimethoprim at high doses and/or for
extended periods of time may cause bone marrow depression manifested
as thrombocytopenia, leukopenia, and/or megaloblastic anemia. If
signs of bone marrow depression occur, the patient should be given
leucovorin; 5 to 15 mg leucovorin daily has been recommended by
some investigators.
IV Infusion
Acute
Since there has been no extensive experience in humans with single
doses of sulfamethoxazole; trimethoprim IV infusion in excess of
25 ml (400 mg trimethoprim and 2000 mg sulfamethoxazole), the maximum
tolerated dos in humans is unknown. Signs and symptoms of overdosage
reported with sulfonamides include anorexia, colic, nausea, vomiting,
dizziness, headache, drowsiness, and unconsciousness. Pyrexia, hematuria,
and crystalluria may be noted. Blood dyscrasias and jaundice are
potential late manifestations of overdosage. Signs of acute overdosage
with trimethoprim include nausea, vomiting, dizziness, headache,
mental depression, confusion, and bone marrow depression.
General principles of treament include the administration of intravenous
fluids if urine output is low and renal function is normal. Acidification
of the urine will increase renal elimination of treimethoprim.
The patient should be monitored with blood counts and appropriate
blood chemistries, including electrolytes. If a significant blood
dyscrasia or jaundice occurs, specific therapy should be instituted
for these complications. Peritoneal dialysis is not effective and
hemodialysis is only moderately effective in eliminating sulfamethoxazole;
trimethoprim.
Chronic
Use of sulfamethoxazole; trimethoprim IV infusion at high doses
and/or for extended periods of any time may cause bone marrow depression
manifested as thrombocytopenia,leukopenia and/or megaloblastic amenia.
If signs of bone marrow depression occur, the patient should be
given leucovorin; 5 to 15 mg leucovorin daily has been recommended
by some investigators.
Animal Toxicity
The LD50 of sulfamethoxazole; trimethoprim IV infusion in mice
is 700 mg/kg or 7.3 ml/kg; in rats and rabbits the LD50 is >500
mg/kg or >5.2 ml/kg. The vehicle produced the same LD50 in each
of these species as the active drug.
The signs and symptoms noted in mice, rats and rabbits with sulfamethoxazole;
trimethroprim IV infusion or its vehicle at the high IV doses used
in acute toxicity studies included ataxia, decreased motor activity,
loss of righting reflex, tremors or convulsions, and/or respiratory
depression.
CONTRAINDICATIONS
Sulfamethoxazole; trimethoprim is contraindicated in patients with
a known hypersensitivity to trimethoprim or sulfonamides and in
patients with documented megaloblastic anemia due to folate deficiency.
Sulfamethoxazole; trimethoprim is also contraindicated in pregnant
patients at term and in nursing mothers, because sulfonamides pass
the placenta and are excreted in the milk and may cause kernicterus.
Sulfamethoxazole; trimethoprim is contraindicated in pediatric patients
less than 2 months of age.
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