Pyrimethamine

Treatment of Toxoplasmosis : Pyrimethamine tablets are indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination.

• 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

See DOSAGE AND ADMINISTRATION section.

• Use of pyrimethamine tablets are 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

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 ). …

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, intravenous, or intramuscular) until normal hematopoiesis is restored. …

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. …

Pregnancy Teratogenic Effects : Pyrimethamine has been shown to be teratogenic in rats when given in oral doses 2.5 times the human dose for treatment of toxoplasmosis. At these doses in rats, there was a significant increase in abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia. …

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. …

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