Generic Name

Pyrimethamine

---

Classification

FDA Approved Indications

• Toxoplasmosis; Malaria (as part of combination therapy)

Mechanism of Action

Pyrimethamine inhibits dihydrofolate reductase, an enzyme involved in folic acid metabolism, thereby inhibiting DNA synthesis in protozoa.

Dosage and Administration

Adult: Varies based on indication; for toxoplasmosis, typical dosage is 75-100 mg initially, then maintenance doses of 25-50 mg daily for weeks to months.

Pediatric: Dose based on body weight; commonly 2.5 mg/kg per day, divided into doses.

Geriatric: Dose adjustments based on renal and hepatic function, increased monitoring recommended.

Renal Impairment: Use with caution; dose adjustments may be necessary.

Hepatic Impairment: Use with caution; monitor hepatic function.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Widely distributed, crosses blood-brain barrier.

Metabolism: Minimal hepatic metabolism.

Excretion: Renal excretion; active metabolites may be excreted via the kidneys.

Half Life: Approximately 3-4 days.

Contraindications

• Hypersensitivity to pyrimethamine or other sulfonamides.

Precautions

• Blood dyscrasias (e.g., anemia, leukopenia), folic acid deficiency, hepatic and renal impairment, pregnancy (category C).

Adverse Reactions - Common

• Nausea, vomiting (Common)
• Rash (Common)

Adverse Reactions - Serious

• Bone marrow suppression leading to anemia, leukopenia, thrombocytopenia (Rare but serious)
• Stevens-Johnson syndrome, toxic epidermal necrolysis (Rare)

Drug-Drug Interactions

• Sulfamethoxazole, other folate antagonists, drugs affecting bone marrow function.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed.
• Report signs of blood disorders, hypersensitivity, or skin reactions immediately.
• Maintain proper hydration.
• Use caution to avoid sun exposure due to photosensitivity.
• Complete entire course of therapy.

Special Considerations

Black Box Warnings:

• Bone marrow suppression and hypersensitivity reactions.

Genetic Factors: Individuals with G6PD deficiency may be at increased risk of hemolytic anemia.

Lab Test Interference: May cause false lab results in certain assays.

Overdose Management

Signs/Symptoms: Severe bone marrow suppression, gastrointestinal symptoms, neurological symptoms.

Treatment: Supportive care, folinic acid (leucovorin) may be administered to mitigate hematologic toxicity.

Storage and Handling

Storage: Store at room temperature (20-25°C); protect from moisture and light.

Stability: Stable under recommended conditions for the shelf life indicated.