Pyrimethamine

DARAPRIM

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What it isDihydrofolate reductase inhibitor selective for the parasite enzyme; toxoplasmosis.

Why this oneIt is first-line for toxoplasmic encephalitis, given with sulfadiazine.

What limits itMegaloblastic anemia and myelosuppression, so leucovorin is co-given throughout. It is teratogenic.

FDA-approved for

toxoplasmosis (~1953)

FDA label

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FDA dosing	Population	Start	Target	Max
Toxoplasmosis	Adults	50-75 mg QD with a sulfonamide	50-75 mg QD x1-3 wk, then reduce to ~half x4-5 wk
Toxoplasmosis	Pediatric	1 mg/kg/day divided BID	reduce to ~half after 2-4 days, continue ~1 month

Renal Undefined

Hepatic Undefined

Instructions

Give with meals to minimize vomiting
Co-administer folinic acid in all patients
Use with a sulfapyrimidine-type sulfonamide (e.g., sulfadoxine)
Younger patients may tolerate higher doses than older individuals

Contraindications

Documented megaloblastic anemia due to folate deficiency

Cautions

Hematologic effects (megaloblastic anemia, leukopenia, thrombocytopenia) can occur even at low doses in some patients
Risk of severe hypersensitivity, especially with concomitant sulfonamide

Adverse reactions

Severe hypersensitivity (Stevens-Johnson syndrome, TEN, erythema multiforme, anaphylaxis) and hyperphenylalaninemia, esp. with a sulfonamide
Anorexia, vomiting
Megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, neutropenia, atrophic glossitis, hematuria, cardiac rhythm disorders
Pulmonary eosinophilia (rare)

Pregnancy No adequate human studies; teratogenic in animals — use only if benefit justifies fetal risk; give folinic acid.

Lactation Undefined

NO BOXED WARNINGS

Principal riskMegaloblastic anemia; leucovorin must be co-given

Cost, est. cash$10–$500/month

Generic entry2020

Classes and tags

Clinical profile

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryUnknown / historical label unavailable

Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.