No

Antimalarial Agent

Prophylaxis of malaria due to susceptible strains of plasmodia; used in conjunction with quinine and sulfadiazine for the treatment of uncomplicated attacks of chloroquine-resistant P. falciparum malaria; used in conjunction with fast-acting schizonticide to initiate transmission control and suppression cure; synergistic combination with sulfonamide in treatment of toxoplasmosis

C

Megaloblastic anemia secondary to folate deficiency; known hypersensitivity to pyrimethamine, chloroguanide; resistant malaria

When used for more than 3-4 days, it may be advisable to administer leucovorin to prevent hematologic complications; monitor CBC and platelet counts every 2 weeks; use with caution in patients with impaired renal or hepatic function or with possible G-6-PD

1% to 10%:

Gastrointestinal: Anorexia, abdominal cramps, vomiting

Hematologic: Megaloblastic anemia, leukopenia, thrombocytopenia, agranulocytosis

<1%: Insomnia, lightheadedness, fever, malaise, seizures, depression, rash, dermatitis, Stevens-Johnson syndrome, erythema multiforme, anaphylaxis, abnormal skin pigmentation, diarrhea, xerostomia, atrophic glossitis, pulmonary eosinophilia

Symptoms of overdose include megaloblastic anemia, leukopenia, thrombocytopenia, anorexia, CNS stimulation, seizures, nausea, vomiting, hematemesis

Following GI decontamination, leucovorin should be administered in a dosage of 5-15 mg/day I.M., I.V., or oral for 5-7 days or as required to reverse symptoms of folic acid deficiency; diazepam 0.1-0.25 mg/kg can be used to treat seizures

Decreased effect: Pyrimethamine effectiveness decreased by acid

Increased effect: Sulfonamides (synergy), methotrexate, TMP/SMX may increase the risk of bone marrow suppression; mild hepatotoxicity with lorazepam

Pyrimethamine tablets may be crushed to prepare oral suspensions of the drug in water, cherry syrup, or sucrose-containing solutions at a concentration of 1 mg/mL; stable at room temperature for 5-7 days

Inhibits parasitic dihydrofolate reductase, resulting in inhibition of vital tetrahydrofolic acid synthesis

Onset of action: Within 1 hour

Absorption: Oral: Well absorbed

Distribution: Widely distributed ; mainly concentrated in blood cells, kidneys, lungs, liver, and spleen; crosses into CSF; crosses placenta; appears in breast milk

Metabolism: Hepatic

Half-life: 80-95 hours

Time to peak serum concentration: Within 1.5-8 hours

Elimination: 20% to 30% excreted unchanged in urine

Malaria chemoprophylaxis (for areas where chloroquine-resistant P. falciparum exists): Begin prophylaxis 2 weeks before entering endemic area:

Children: 0.5 mg/kg once weekly; not to exceed 25 mg/dose

or

Children:

<4 years: 6.25 mg once weekly

4-10 years: 12.5 mg once weekly

Children >10 years and Adults: 25 mg once weekly

Dosage should be continued for all age groups for at least 6-10 weeks after leaving endemic areas

Chloroquine-resistant P. falciparum malaria (when used in conjunction with quinine and sulfadiazine):

Children:

<10 kg: 6.25 mg/day once daily for 3 days

10-20 kg: 12.5 mg/day once daily for 3 days

20-40 kg: 25 mg/day once daily for 3 days

Adults: 25 mg twice daily for 3 days

Toxoplasmosis:

Infants for congenital toxoplasmosis: Oral: 1 mg/kg once daily for 6 months with sulfadiazine then every other month with sulfa, alternating with spiramycin.

Children: Loading dose: 2 mg/kg/day divided into 2 equal daily doses for 1-3 days (maximum: 100 mg/day) followed by 1 mg/kg/day divided into 2 doses for 4 weeks; maximum: 25 mg/day

With sulfadiazine or trisulfapyrimidines: 2 mg/kg/day divided every 12 hours for 3 days followed by 1 mg/kg/day once daily or divided twice daily for 4 weeks given with trisulfapyrimidines or sulfadiazine

Adults: 50-75 mg/day together with 1-4 g of a sulfonamide for 1-3 weeks depending on patient's tolerance and response, then reduce dose by 50% and continue for 4-5 weeks or 25-50 mg/day for 3-4 weeks

In HIV, life-long suppression is necessary to prevent relapse; leucovorin (5-10 mg/day) is given concurrently

CBC, including platelet counts

May rarely cause drowsiness, insomnia, or depression

May cause leukopenia; use caution with clozapine and carbamazepine; mild hepatotoxicity associated with concurrent usage of lorazepam

No information available to require special precautions

Atrophic glossitis has been reported

Take on schedule as directed and take full course of therapy. If used for prophylaxis, begin 2 weeks before traveling to endemic areas, continue during travel period, and for 6-10 weeks following return. Regular blood tests will be necessary during therapy. You may experience GI distress (frequent small meals may help). You may experience dizziness, changes in mentation, insomnia, headache, or visual disturbances (use caution when driving or operating dangerous machinery). Report unresolved nausea or vomiting, anorexia, skin rash, fever, sore throat, unusual bleeding or bruising, yellowing of skin or eyes, and change in color of urine or stool. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Leucovorin may be administered in a dosage of 3-9 mg/day for 3 days or 5 mg every 3 days or as required to reverse symptoms or to prevent hematologic problems due to folic acid deficiency

Tablet: 25 mg

Pyrimethamine tablets may be crushed to prepare oral suspensions of the drug in water, cherry syrup or sucrose-containing solutions at a concentration of 1 mg/mL; stable at room temperature for 5-7 days

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