Pyrimethamine (Page 2 of 2)

ADVERSE REACTIONS

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.

To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

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.

DOSAGE AND ADMINISTRATION

For Treatment of Toxoplasmosis: The dosage of pyrimethamine tablets for the treatment of toxoplasmosis must be carefully adjusted so as to provide maximum therapeutic effect and a minimum of side effects. At the dosage required, there is a marked variation in the tolerance to the drug. Young patients may tolerate higher doses than older individuals. Concurrent administration of folinic acid is strongly recommended in all patients.

The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g. sulfadoxine. This dosage is ordinarily continued for 1 to 3 weeks, depending on the response of the patient and tolerance to therapy. The dosage may then be reduced to about one half that previously given for each drug and continued for an additional 4 to 5 weeks.

The pediatric dosage of pyrimethamine tablets is 1 mg/kg/day divided into 2 equal daily doses; after 2 to 4 days this dose may be reduced to one half and continued for approximately 1 month. The usual pediatric sulfonamide dosage is used in conjunction with pyrimethamine tablets.

HOW SUPPLIED

Pyrimethamine Tablets, USP are available as following:

25 mg — White, round, scored tablets debossed with “2P” and “T” on one side and plain on the other side in bottles of 30 (NDC 0480-3720-56) and 100 (NDC 0480-3720-01).

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

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.

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

Manufactured For:

Teva Pharmaceuticals

Parsippany, NJ 07054

Iss. 8/2021

Packaging Label Principal Display Panel

NDC 0480-3720-56

Pyrimethamine Tablets, USP 25 mg

Rx only

30 Tablets

PYRIMETHAMINE pyrimethamine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0480-3720 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PYRIMETHAMINE (PYRIMETHAMINE) PYRIMETHAMINE 25 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN MAGNESIUM STEARATE MANNITOL

Product Characteristics Color white Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code 2P;T Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:0480-3720-56 30 TABLET in 1 BOTTLE, PLASTIC None 2 NDC:0480-3720-01 100 TABLET in 1 BOTTLE, PLASTIC None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA215506 12/15/2021

Labeler — Teva Pharmaceuticals, Inc. (022629579)

Revised: 08/2021 Teva Pharmaceuticals, Inc.