Pyrimethamine

Pyrimethamine is an antiparasitic compound available in tablet form for oral administration. Each scored tablet contains 25 mg pyrimethamine and the inactive ingredients corn and potato starch, lactose, and magnesium stearate.

Pyrimethamine, known chemically as 5-(4- chlorophenyl)-6-ethyl-2, 4-pyrimidinediamine, has the following structural formula:

C₁₂H₁₃CIN₄          
Mol. Wt. 248.7
Structural Formula

Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins.

Use of pyrimethamine 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.

The dosage of pyrimethamine required for the treatment of toxoplasmosis has a narrow therapeutic window. If signs of folate deficiency develop (see ADVERSE REACTIONS), reduce the dosage or discontinue the drug according to the response of the patient. Folinic acid (leucovorin) should be administered in a dosage of 5 to 15 mg daily (orally, IV, or IM) until normal hematopoiesis is restored. Data in 2 humans indicate that pyrimethamine may be carcinogenic; a 51-year-old female who developed chronic granulocytic leukemia after taking pyrimethamine for 2 years for toxoplasmosis³ and a 56-year-old patient who developed reticulum cell sarcoma after 14 months of pyrimethamine for toxoplasmosis.⁴

Pyrimethamine has been reported to produce a significant increase in the number of lung tumors in mice when given intraperitoneally at doses of 25 mg/kg.⁵

Pyrimethamine should be kept out of the reach of infants and children as they are extremely susceptible to adverse effects from an overdose. Deaths in pediatric patients have been reported after accidental ingestion.

Hypersensitivity reactions, occasionally severe (such as Stevens- Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and anaphylaxis), and hyperphenylalaninemia, can occur particularly when pyrimethamine is administered concomitantly with a sulfonamide. Consult the complete prescribing information for the relevant sulfonamide for sulfonamide-associated adverse events. With doses of pyrimethamine used for the treatment of toxoplasmosis, anorexia and vomiting may occur. Vomiting may be minimized by giving the medication with meals; it usually disappears promptly upon reduction of dosage. Doses used in toxoplasmosis may produce megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, neutropenia, atrophic glossitis, hematuria, and disorders of cardiac rhythm

Hematologic effects, however, may also occur at low doses in certain individuals (see PRECAUTIONS; General).

Pulmonary eosinophilia has been reported rarely.

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 earned 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.

White, scored tablets containing 25 mg pyrimethamine, imprinted with “Daraprim” and “A3A" in bottles of 100 (NDC 72647-330-01) and bottles of 30 (NDC 72647-330-03).

Store at 15° to 25°C (59° to 77°F) in a dry place and protect from light.

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, Specter JKS, et al. Validation and characterization of the L5178Y/TK +/- mouse lymphoma mutagen assay system. Mut Res. 1979;59:61-108.

Distributed by:
Oakrum Pharma, LLC, St. Louis, MO 63127

005555-PI-001
022497
Rev. 01/2019

NDC 72647-330-01

OAKRUM PHARMA

Pyrimethamine Tablets, 25 mg

Each scored tablet contains 25 mg

Rx only

100 Tablets

Warning: Potent Drug - do not exceed recommended dosage.

Store at 15° to 25°C (59° to 77°F) in a dry place.
Dispense in tight, light-resistant container as defined in the USP.

Dosage: See accompanying prescribing information.

Distributed by:
Oakrum Pharma, LLC
St. Louis, MO 63127
Rev. 1/2019

022496

NDC 72647-330-03
 
OAKRUM PHARMA

Pyrimethamine Tablets, 25 mg

Each scored tablet contains 25 mg

Rx only
 
30 Tablets

Warning: Potent Drug - do not exceed recommended dosage.

Store at 15° to 25°C (59° to 77°F) in a dry place.
Dispense in tight, light-resistant container as defined in the USP.

Dosage: See accompanying prescribing information.

Distributed by:
Oakrum Pharma, LLC
St. Louis, MO 63127
Rev. 1/2019

022495