indication

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.

biotransformation

Hepatic

absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration

half life

96 hours

drug interactions

Artemether: Pyrimethamine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.

Lumefantrine: Pyrimethamine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Tamoxifen: Pyrimethamine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Pyrimethamine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pyrimethamine is initiated, discontinued, or dose changed.

Tramadol: Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production.