• Used in combination with other antimalarials in the treatment of chloroquine-resistant malaria.
• Used in combination with a sulfonamide in the treatment of toxoplasmosis.

Unlabeled Uses:

• Used in combination with other agents (sulfonamides, dapsone) in the treatment of Pneumocystis jirovecii pneumonia.

Contraindicated in:

• Hypersensitivity
• OB: First 14–16 wk of pregnancy
• Megaloblastic anemia caused by folate deficiency
• Concurrent folate antagonist therapy (because of risk of megaloblastic anemia)
• Tablets contain lactose and potato starch and should be avoided in patients with known hypersensitivity/intolerance.

Use Cautiously in:

• History of seizures (high doses)
• Underlying anemia or bone marrow depression
• Hepatic impairment
• G6PD deficiency
• OB: Pregnancy >16 wk (may require concurrent leucovorin)
• Lactation: Large doses to mother may cause folic acid deficiency in infant.

CNS: SEIZURES (HIGH DOSES), headache, insomnia, light-headedness, malaise, mental depression.

Resp: dry throat, pulmonary eosinophilia.

CV: ARRHYTHMIAS (LARGE DOSES).

GI: atrophic glossitis (high doses), anorexia, diarrhea, nausea.

GU: hematuria.

Derm: abnormal pigmentation, dermatitis.

Hemat: megaloblastic anemia (high doses), neutropenia, pancytopenia, thrombocytopenia.
Misc: fever.

Drug-Drug:

• ↑risk of bone marrow depression with other bone marrow depressants, including antineoplastics, proguanil, or radiation therapy.
• ↑risk of megaloblastic anemia with folate antagonists (methotrexate); concurrent use should be avoided.

• Tablets: 25 mg;

Treatment of Malaria

• PO (Adults and Children >10 yr): 50 mg/day for 2 days, then 25 mg once weekly in combination with other agents.
• PO (Children 4–10 yr): 25 mg daily for 2 days, then 12.5 mg once weekly in combination with other agents.

Toxoplasmosis

• PO (Adults): 50–200 mg/day for 1–2 days, followed by 25–50 mg/day for 2–6 wk; given with a sulfonamide.
• PO (Children): 1 mg/kg/day for 1–3 days, then 0.5 mg/kg/day for 4–6 wk; given with a sulfonamide.

Toxoplasmosis in AIDS Patients

• PO (Adults): 100–200 mg/day for 1–2 days, followed by 50–100 mg/day for 3–6 wk, then 25–50 mg/day for life; given with clindamycin or sulfadiazine.

Daraprim

• Binds to an enzyme in the protozoa, which results in depletion of folic acid.

• Death and arrested growth of susceptible organisms (protozoa).

Therapeutic Classification: antimalarials, antiprotozoals

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed with high concentrations achieved in blood cells, kidneys, lungs, liver, and spleen. Some enters CSF (13–26% of serum levels). Crosses the placenta and enters breast milk.

Metabolism/Excretion: Mostly metabolized by the liver. 20–30% excreted unchanged by the kidneys.

Half-life: 4 days (↓ in patients with AIDS).

(blood levels)

†Suppressive levels.

• Instruct patient to take medication as directed on a regular schedule and continue full course of therapy, even if feeling better. Take missed doses as soon as remembered unless almost time for next dose; do not double doses.
• Advise patient to notify health care professional promptly if sore throat, pallor, purpura, or glossitis occurs. Instruct patient to stop taking pyrimethamine and notify health care professional immediately at the first sign of a skin rash or if no improvement is seen within a few days.
• Emphasize the importance of lab tests at scheduled intervals, especially in patients taking high doses. Tests should not be delayed or missed.

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