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Pyrimethamine

Pronunciation: pihr-ih-METH-ah-meen
Class: Folic acid antagonist

Trade Names

Daraprim
- Tablets 25 mg

Pharmacology

Pyrimethamine is a folic acid antagonist, and the therapeutic action is based on differential requirements between host and parasite for nucleic acid precursors involved in growth.

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Pharmacokinetics

Absorption

Well absorbed, reaching C max in 2 to 6 h.

Distribution

Plasma protein binding is 87%.

Elimination

Plasma t ½ is approximately 96 h.

Indications and Usage

Treatment of toxoplasmosis (in conjunction with a sulfonamide); treatment of acute malaria (in conjunction with a schizonticide [eg, chloroquine, quinine] but a sulfonamide [eg, sulfadoxine] will initiate transmission control and suppression of susceptible strains of plasmodia); chemoprophylaxis of malaria.

Contraindications

Patients with documented megaloblastic anemia caused by folate deficiency; hypersensitivity to any component of the product.

Dosage and Administration

Acute Malaria
Adults and Children older than 10 yr of age

PO 50 mg/day for 2 days.

Children 4 to 10 yr of age

PO 25 mg/day for 2 days. Follow with the once weekly chemoprophylaxis regimen described below. Regimens that include suppression should be extended through any characteristic periods of early recrudescence and late relapse (for at least 10 wk).

Chemoprophylaxis of Malaria
Adults and Children older than 10 yr of age

PO 25 mg once/wk.

Children 4 to 10 yr of age

PO 12.5 mg once/wk.

Infants and Children younger than 4 yr of age

PO 6.25 mg once/wk.

Toxoplasmosis
Adults

PO Start with 50 to 75 mg/day, together with 1 to 4 g of a sulfapyrimidine type sulfonamide (eg, sulfadoxine). Continue for 1 to 3 wk, depending on response and tolerance. Dosage may then be reduced to about one-half that previously given for each drug and continued for an additional 4 to 5 wk.

Children

PO 1 mg/kg/day in 2 equally divided doses; after 2 to 4 days, reduce dose to one-half and continue for about 1 mo. Coadminister the usual pediatric sulfonamide dosage with pyrimethamine.

General Advice

Administer prescribed dose with food to minimize anorexia and vomiting.

Storage/Stability

Store tablets at controlled room temperature (59° to 77°F). Protect from light and moisture.

Drug Interactions

Antifolate drugs or agents associated with myelosuppression (eg, cytostatic agents [eg, methotrexate], sulfonamides, trimethoprim-sulfamethoxazole, proguanil, zidovudine)

May increase risk of bone marrow suppression.

Lorazepam

Mild hepatotoxicity has been reported.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Rhythm disorders.

GI

Anorexia; vomiting (with large doses); atrophic glossitis.

Hematologic

Megaloblastic anemia; leukopenia; thrombocytopenia; pancytopenia; hematuria.

Miscellaneous

Hypersensitivity (may include Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, anaphylaxis); pulmonary eosinophilia (rare).

Precautions

Monitor

CBC

Asses CBC, including platelet count, before starting therapy and semi-weekly thereafter in patient being treated for toxoplasmosis. If signs of folate deficiency develop (eg, megaloblastic changes, glossitis), discontinue pyrimethamine and administer folinic acid (leucovorin) until normal hematopoiesis is restored.


Pregnancy

Category C .

Lactation

Excretion in breast milk.

Children

See Route/Dosage section.

Elderly

Use with caution, usually starting at the low end of the dosing range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Accidental ingestion

Keep out of the reach of infants and children as they are extremely susceptible to adverse reactions from an overdose; death may occur.

Folic acid deficiency

The dose of pyrimethamine required to treat toxoplasmosis approaches the toxic level. Use with caution in possible folate deficiency.

Hemolytic anemia

Large doses may precipitate hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.

Resistance

Resistance to pyrimethamine is prevalent worldwide; it is not considered suitable as a prophylactic agent for travelers to most areas.

Overdosage

Symptoms

Convulsions, abdominal pain, nausea, severe and repeated vomiting (including hematemesis), CNS toxicity (manifested as excitability), generalized and prolonged convulsions, respiratory depression, circulatory collapse, death.

Patient Information

  • Advise patient to continue to take any concurrently prescribed therapy (eg, folinic acid, sulfonamide) in order to achieve max benefit and reduce risk of adverse reactions.
  • Advise patient to take each dose with food to reduce chances of appetite loss and vomiting.
  • Advise patient that protective clothing, insect repellants, and bednets are important components of malaria prophylaxis.
  • Advise patient to stop using and contact health care provider immediately if skin rash, sore throat, paleness, red or inflamed tongue or mouth, or small purple spots under skin develop.
  • Advise women of childbearing potential to use effective contraception while taking pyrimethamine.
  • Advise patient that if a febrile illness develops during or after return from a malaria-endemic area, to seek health care and inform health care provider of possible malaria exposure.

Copyright © 2009 Wolters Kluwer Health.

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