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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