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DRUG INTERACTIONS
Drug Interactions: Pyrimethamine may be used with sulfonamides, quinine and
other antimalarials, and with other antibiotics. However, the
concomitant use of other antifolic drugs or agents associated
with myelosuppression including sulfonamides or
trimethoprim-sulfamethoxazole combinations, proguanil,
zidovudine, or cytostatic agents (e.g., methotrexate), while the
patient is receiving pyrimethamine, may increase the risk of
bone marrow suppression. If signs of folate deficiency develop,
pyrimethamine should be discontinued. Folinic acid (leucovorin)
should be administered until normal hematopoiesis is restored
(see WARNINGS). Mild hepatotoxicity has been reported in some
patients when lorazepam and pyrimethamine were administered
concomitantly.
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OVERDOSAGE
Following the ingestion of 300 mg or more of
pyrimethamine, gastrointestinal and/or central nervous system signs may
be present, including convulsions. The initial symptoms are usually
gastrointestinal and may include abdominal pain, nausea, severe and
repeated vomiting, possibly including hematemesis. Central nervous
system toxicity may be manifest by initial excitability, generalized and
prolonged convulsions which may be followed by respiratory depression,
circulatory collapse, and death within a few hours. Neurological
symptoms appear rapidly (30 minutes to 2 hours after
drug ingestion), suggesting that in gross overdosage pyrimethamine has a
direct toxic effect on the central nervous system.
The fatal dose is variable, with the smallest reported fatal
single dose being 375 mg. There are, however, reports of
pediatric patients who have recovered after taking 375 to
625 mg.
There is no specific antidote to acute pyrimethamine poisoning.
In the event of overdosage, symptomatic and supportive measures should
be employed. Gastric lavage is recommended and is effective if carried
out very soon after drug ingestion. Parenteral diazepam may be used to
control convulsions. Folinic acid should be administered within
2 hours of drug ingestion to be most effective in counteracting
the effects on the hematopoietic system (see WARNINGS). Due to the long half-life of pyrimethamine, daily
monitoring of peripheral blood counts is recommended for up to several
weeks after the overdose until normal hematologic values are
restored.
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CONTRAINDICATIONS
Use of DARAPRIM is contraindicated in patients with known
hypersensitivity to pyrimethamine or to any component of the
formulation. Use of the drug is also contraindicated in patients with
documented megaloblastic anemia due to folate deficiency.
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REFERENCES
1. Eyles DE,
Coleman N. Synergistic effect of sulfadiazine and Daraprim against
experimental toxoplasmosis in the mouse. Antibiot Chemother
1953;3:483-490.
2. Jacobs L,
Melton ML, Kaufman HE. Treatment of experimental ocular toxoplasmosis.
Arch Ophthalmol.
1964;71:111-118.
3. Jim RTS,
Elizaga FV. Development of chronic granulocytic leukemia in a patient
treated with pyrimethamine. Hawaii Med J. 1977;36:173-176.
4. Sadoff L.
Antimalarial drugs and Burkitt’s lymphoma. Lancet. 1973;2:1262-1263.
5. Bahna L.
Pyrimethamine. LARC Monogr Eval Carcinog
Risk Chem. 1977;13:233-242.
6. Clive
D, Johnson KO, Spector JKS, et al. Validation and characterization of
the L5178Y/TK +/- mouse lymphoma mutagen
assay system. Mut Res. 1979;59:61-108.
Distributed by:
Amedra Pharmaceuticals LLC
Horsham, PA 19044
LB# 801-03 Rev. 10-2014
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