pyrimethamine

REMS

Toxoplasmosis (in combination with a sulfonamide).

Unlabeled Use:

Pneumocystis jiroveciipneumonia (in combination with sulfonamides or dapsone).

Action ⬆ ⬇

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

Therapeutic effects:

Death and arrested growth of susceptible organisms (protozoa).

Pharmacokinetics ⬆ ⬇

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).

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

Half-Life: 4 days (↓ in patients with HIV).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	2 wk‡

‡Suppressive levels.

Contraind./Precautions ⬆ ⬇

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;
Lactation: Lactation.

Use Cautiously in:

History of seizures (high doses);
Underlying anemia or bone marrow depression;
Hepatic impairment;
OB: Pregnancy >16 wk (may require concurrent leucovorin).

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS (LARGE DOSES)

Derm: abnormal pigmentation, dermatitis

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

GU: hematuria

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

Resp: dry throat, pulmonary eosinophilia

Misc: fever

Interactions ⬆ ⬇

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.

Route/Dosage ⬆ ⬇

Toxoplasmosis (in Patients without HIV)

PO (Adults ): 50–200 mg once daily for 1–2 days, followed by 25–50 mg once daily for 2–6 wk.
PO (Children ): 1 mg/kg once daily for 1–3 days, then 0.5 mg/kg once daily for 4–6 wk.

Toxoplasmosis (in Patients with HIV)

PO (Adults ): 100–200 mg once daily for 1–2 days, followed by 50–100 mg once daily for 3–6 wk, then 25–50 mg once daily for life.

Availability ⬆ ⬇

(Generic available)

Tablets: 25 mg

Assessment ⬆ ⬇

Assess patient for improvement in signs and symptoms of infection daily during therapy.

Lab Test Considerations:

Monitor CBC and platelet count periodically during therapy and semiweekly in patients with toxoplasmosis. May cause ↓ WBC and platelet counts.

Implementation ⬆ ⬇

Leucovorin may be administered concurrently to prevent folic acid deficiency and restore normal hematopoiesis.
PO: Administer with milk or meals to minimize GI distress.
- Tablets may be crushed and mixed with saline or with other vehicles by pharmacist for patients with difficulty swallowing.

Patient/Family Teaching ⬆ ⬇

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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding.
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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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇