Generic
Pyrimethamine
1 brands available in the market
At a glance
Pyrimethamine is a folic acid antagonist used for acute malaria (in combination with sulfonamide), malaria prophylaxis, and toxoplasmosis.
Description
Pyrimethamine is a folic acid antagonist structurally similar to trimethoprim. It inhibits parasitic dihydrofolate reductase, thus inhibiting vital tetrahydrofolic acid synthesis. It is active against pre-erythrocytic forms and is also a slow-acting schizontocide.
Indications
- Acute malaria (in combination with sulfonamide)
- Malaria prophylaxis
- Toxoplasmosis
Therapeutic class
Anti-malarial drugs
Pharmacological class
Folic Acid Antagonist
Pharmacology
Pyrimethamine inhibits parasitic dihydrofolate reductase, preventing tetrahydrofolic acid synthesis essential for parasite growth and replication. It is active against pre-erythrocytic forms and is a slow-acting schizontocide.
Mechanism of action
Prevents malaria parasite growth by inhibiting parasitic dihydrofolate reductase.
Dosage
Adult Dose (Oral):
- Acute malaria: 75 mg pyrimethamine + 1.5 g sulfadoxine (single dose)
- Malaria prophylaxis: 25 mg once weekly; start 1-2 days before arrival in endemic area, continue for 4-6 weeks after leaving
- Toxoplasmosis: 50-75 mg/day + 1-4 g sulfadiazine/day (1-3 weeks); then half dose for 4-5 weeks
Pediatric Dose (Oral):
- Acute malaria (7-13 years): 50 mg + 1 g sulfadoxine; (1-6 years): 25 mg + 500 mg sulfadoxine; (5-11 months): 12.5 mg + 250 mg sulfadoxine
- Malaria prophylaxis (<4 years): 6.25 mg/week; (4-10 years): 12.5 mg/week; (>10 years): 25 mg/week
- Congenital toxoplasmosis (>2 months): Loading 2 mg/kg/day for 2 days; Maintenance 1 mg/kg/day (2-6 months) then 1 mg/kg 3 times/week
Administration
- Take with food
- Take at the same time each day
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Side Effects:
- Skin rash
- Macrocytic anemia (high dose)
- Leukopenia
- Thrombocytopenia
- Megaloblastic anemia
- Pancytopenia
- Abdominal pain
- Vomiting
- Atrophic glossitis
- Depression, fever, insomnia, lightheadedness
- Potentially fatal: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (with sulfadoxine at large doses)
Precautions & warnings
- Caution in renal or hepatic impairment
- Folate deficiency
- Monitor blood and platelet counts every 2 weeks with prolonged treatment and large doses
- Discontinue use if skin reactions, sore throat, or shortness of breath occurs
- Do not use during pregnancy
- Do not use during lactation
Contraindications
- Hypersensitivity to pyrimethamine or sulfonamides
- Resistant malaria
- Megaloblastic anemia secondary to folate deficiency
- Pregnancy and lactation
Drug interactions
- Lorazepam: May induce hepatotoxicity
- Proguanil, sulfonamides, zidovudine, cytostatic agents: Increased risk of bone marrow suppression
- Co-trimoxazole or other sulfonamides: Increased risk of serious pancytopenia and megaloblastic anemia
Food interactions
It is not known whether it is safe to consume alcohol with Pyrimethamine.
Use in pregnancy
Use in Pregnancy: Unsafe during pregnancy; evidence of risk to the fetus; consult your doctor.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Not safe during breastfeeding; enters breast milk; do not nurse.
Pediatric use
Pediatric dose based on age and weight; consult your doctor.
Geriatric use
Caution required in elderly patients; dose adjustment may be needed.
Renal / hepatic impairment
Renal Impairment: Caution in kidney disease; dose adjustment may be needed; consult your doctor.
Hepatic Impairment: Caution in liver disease; dose adjustment may be needed; consult your doctor.
Overdose effects
Overdose: Folate deficiency symptoms (megaloblastic anemia, pancytopenia); treatment: folic acid or leucovorin, symptomatic supportive care.
Storage conditions
Store in a cool and dry place, away from light; keep out of reach of children.
Chemical structure
Pyrimethamine