2010/06/14

Pyrimethamine

International name:
Pyrimethamine (Pyrimethamine)

Group Affiliation:
Antimalarial

Description of the active substance (INN):
Pyrimethamine

Dosage form:
Tablets

Mode of action:
Protivoprotozoynoe means; has antimalarial and antitoksoplazmoidnoe action. Blocks folatreduktazu, transforming folic acid folinic. It is active against parasites (Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, respectively, causing a 3-day, tropical, and 4-day malaria) and the causative agent of toxoplasmosis (Toxoplasma gondii), has schizontocide action. Shows activity against both parasites are in the bloodstream (though somewhat weaker than the 4-aminohinoliny), and in respect of parasites located in hepatocytes. It has no effect on the sexual forms of Plasmodium falciparum in the human body (devoid gamontotsidnoy activity), but inhibits fertilization gamont in the body vector (gamontostaticheskoe action). It has a sporicidal action against Plasmodium falciparum and Plasmodium vivax, and may reduce the cyclical transmission with wide application. The activity against the causative agent of toxoplasmosis is largely enhanced when it is combined with a sulphonamide.

Indications:
Malaria, toxoplasmosis (congenital and acquired), uveitis (toxoplasmic or unknown etiology).

Contraindications:
Hypersensitivity, megaloblastic B12-deficient anemia associated with deficiency of folic kisloty.C caution. Hepatic and / or renal failure, folate-deficient state.

Adverse effects:
Allergic reactions, rashes, insomnia, nausea, abdominal pain spastic character, vomiting, diarrhea, arrhythmia, hematuria, megaloblastic B12-deficient anemia, depression kosnomozgovogo blood (thrombocytopenia, leukopenia), headache, dizziness, dry mouth or throat, fever, dermatitis, hyperpigmentation, depression, circulatory collapse, ulceration of the oral mucosa, large seizures (in the predisposition to epilepsy) in newborns - giperfenilalaninemiya; in elderly patients during prolonged therapy (1.5 and 2 years) - malignant disease (granulocytic leukemia, retikulyarnokletochnaya sarcoma). overdosage. Symptoms: nausea, vomiting, convulsions, circulatory disorders, depression of the respiratory center. Specific antidote exists. The minimum lethal dose - 250-300 mg (there are reports of recovery of children who swallowed a 375-625 mg). Treatment: symptomatic, early gastric lavage. Gastric lavage may have a positive effect only for 2 hours after ingestion. To combat a possible deficiency of folic need to take calcium folinat to the disappearance of symptoms of intoxication. Because the side effects associated with leukopenia, may occur with the maximum delay of 7-10 days, but calcium folinatom should continue throughout the period of greatest risk.

Dosage and administration:
Ext. Malaria prevention: adults and children over 10 years - 25 mg 1 time per week for children from 5 to 10 years - 12.5 mg 1 time per week. Prophylaxis should begin shortly before or immediately after arrival in the endemic area (1 time per week). Upon returning to the area where there is no danger of contracting malaria, taking the drug at this dose should be continued for the next 4 weeks. Malaria Treatment: appoint simultaneously with sulphonamide sverhdlitelnogo action - sulfalenom or sulfadoxine. Adults and children over 14 years - 50-75 mg pyrimethamine and 1-1.5 g sulfalena or sulfadoxine for 1 admission. Children: 1 reception for the scheme (pyrimethamine, or sulfadoxine sulfalen respectively): 9-14 years - 50 mg, 1 g; 4-8 years - 25 mg, 500 mg; under 4 years old - 12.5 mg, 250 mg. Treatment of toxoplasmosis: a comprehensive treatment sulphonamide long and sverhdlitelnogo action (sulfadiazine). Duration of treatment - 3-6 weeks, if you want to continue treatment should be done 2 weeks break between courses. Adults and children over 6 years - an initial dose of 50 mg / day, in the future - 25 mg / day, sulfadiazine - 150 mg / kg (maximum dose - 4 g / day) in 4 admission. Children 2-6 years: initial dose - 2 mg / kg (maximum dose - 50 mg), then - 1 mg / kg / day (maximum dose - 25 mg) sulfadiazine - 150 mg / kg (maximum dose - 2 grams ) in 4 admission. Children from 10 months to 2 years: pyrimethamine - 12.5 mg, sulfadiazine - 150 mg / kg (maximum dose - 1.5 g) in 4 admission. Uveitis: the first 3 days - 100 mg, then - at 50 mg / day.

Cautions:
In the treatment of toxoplasmosis should be additionally appoint folate to reduce the risk of bone marrow suppression. Each week during the treatment period and within 2 weeks of its completion should be a common blood test. If signs of folic deficit - the oppression of bone marrow hematopoiesis - treatment must be interrupted, and assign calcium folinat. Receiving sulfanilamidov must be accompanied by the consumption of adequate amounts of fluid to minimize the risk of crystalluria.

Interaction:
Compatible with sulfonamides, quinine. Intensifies antifolievye influence of inhibitors of folic exchange. Enhances mielosupressornoe action of cytostatics, especially methotrexate, which has antifolatnym effect, as well as all drugs which depress bone marrow hemopoiesis. Patients suffering from acute myelotoxicity anemia, a joint reception with daunorubicin and cytosine-arabinose causes a fatal bone marrow aplasia. Increases toxicity of quinidine, indirect anticoagulants (displaces from its association with proteins). Simultaneous reception lorazepam cause toxic liver damage. In children with leukemia and defeat CNS against the simultaneous administration of methotrexate may have convulsions.