Brands, Medical Use, Clinical Data
Drug Category
- Antiprotozoals
- Antimalarials
- Folic Acid Antagonists
Dosage Forms
Brands / Synonyms
CD; Chloridin; Chloridine; Chloridyn; Darachlor; Daraclor; Darapram; Daraprim; Daraprime; Diaminopyritamin; Disulone; Erbaprelina; Ethylpyrimidine; Fansidar; Khloridin; Malacid; Malocid; Malocide; Maloprim; Pirimecidan; Pirimetamin; Pirimetamina; Primethamine; Pyremethamine; Pyrimethamin; Pyrimethamine Hcl; Tindurin; Tinduring
Indications
For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
Pharmacology
Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.
Mechanism of Action
Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
Absorption
Well absorbed with peak levels occurring between 2 to 6 hours following administration
Toxicity
Not Available
Biotrnasformation / Drug Metabolism
Hepatic
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.
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 sulfon-amides or trimethoprim-sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents
(e.g., methotrex-ate) 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. Mild hepatotoxicity has been reported in some patients when
lorazepam and pyrimethamine were administered concomitantly.
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