PYRIMETHAMINE
(peer-i-meth'a-meen)
Daraprim
Classifications: antiinfective; antimalarial
Prototype: Chloroquine
Pregnancy Category: C

Availability

25 mg tablets

Actions

Long-acting folic acid antagonist chemically related to metabolite of chloroguanide. Selectively inhibits action of dehydrofolic reductate in parasites with resulting blockade of folic acid metabolism.

Therapeutic Effects

No gametocidal activity but prevents development of fertilized gametes in the mosquito and thus helps to prevent transmission of malaria. Exhibits little value as single agent in treatment of acute primary malarial attack because action against blood-borne schizonts is slow in onset. Cross-resistance with chloroguanide may occur.

Uses

Prophylaxis of malaria due to susceptible strains of plasmodia. May be used conjointly with fast-acting antimalarial (e.g., chloroquine, quinacrine, quinine) to initiate transmission control and suppressive cure. Used with a sulfonamide to provide synergistic action in treatment of toxoplasmosis.

Contraindications

Chloroguanide-resistant malaria; hypersensitivity to sulfonamides; megaloblastic anemia caused by folate deficiency; lactation; children <2 mo; pregnancy (category C).

Cautious Use

Patients with convulsive disorders receiving high doses of an anticonvulsant (e.g., phenytoin).

Route & Dosage

Malaria Chemoprophylaxis
Adult: PO 25 mg once/wk
Child: PO <4 y, 6.25 mg once/wk; 4–10 y, 12.5 mg once/wk; >10 y, 25 mg once/wk

Toxoplasmosis
Adult: PO 50–75 mg/d with a sulfonamide for 1–3 wk, then decrease dose by half and continue for 1 mo
Child: PO 1 mg/kg/d divided into 2 doses with a sulfonamide for 1–3 wk, then decrease to 0.5 mg/kg/d for 1 mo (max: 25 mg/d)

Administration

Oral

Minimize GI distress by giving with meals. If symptoms persist, dosage reduction may be necessary.
Give on same day each week for malaria prophylaxis. Begin when individual enters malarious area and continue for 10 wk after leaving the area.

Adverse Effects (1%)

GI: Anorexia, vomiting, atrophic glossitis, abdominal cramps, diarrhea. Skin: Skin rashes. Hematologic: Folic acid deficiency (megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, diarrhea). CNS: CNS stimulation including convulsions, respiratory failure.

Interactions

Drug: Folic acid, para -aminobenzoic acid (PABA) may decrease effectiveness against toxoplasmosis.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 2 h. Distribution: Concentrates in kidneys, lungs, liver, and spleen; distributed into breast milk. Elimination: Excreted slowly in urine; excretion may extend over 30 d or longer. Half-Life: 54–148 h.

Nursing Implications

Assessment & Drug Effects

Monitor patient response closely. Dosages required for treatment of toxoplasmosis approach toxic levels.
Lab tests: Perform blood counts, including platelets, twice weekly during therapy.
Withhold drug and notify physician if hematologic abnormalities appear.

Patient & Family Education

Be aware that folic acid deficiency may occur with long-term use of pyrimethamine. Report to physician weakness, and pallor (from anemia), ulcerations of oral mucosa, superinfections, glossitis; GI disturbances such as diarrhea and poor fat absorption, fever. Folate (folinic acid) replacement may be prescribed. Increase food sources of folates (if allowed) in diet.
Do not breast feed while taking this drug.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug