Drug reference

Pyrimethamine

Antimetabolite · Antiprotozoal, Antimalarial

AntimetaboliteAntiprotozoal, AntimalarialATC null

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

5 major

SEVERE in our sources

PREGNANCY

Best avoided during pregnancy (when used in combination with sulfadoxine) until more information is available; specialist advice should be sought.

FDA category + note

Top interactionssee all 8 →

SulfonamidesSevereTextbookG&G 14e · p1295
AuranofinSevereDatabaseDDInter
AurothioglucoseSevereDatabaseDDInter
DeferiproneSevereDatabaseDDInter

Mechanism

Pyrimethamine is a folate antagonist. It works by inhibiting dihydrofolate reductase, an enzyme critical for the synthesis of tetrahydrofolic acid. This disruption ultimately impairs DNA synthesis, thereby inhibiting the growth of susceptible protozoa.

Indications

Toxoplasmosis (in combination with sulfadiazine, clindamycin, clarithromycin, or azithromycin), particularly toxoplasma choroidoretinitis, in immunosuppressed patients, and for toxoplasmic encephalitis in AIDS patients.Treatment of falciparum malaria (in combination with sulfadoxine and/or quinine) when parasites are likely to be sensitive (unlicensed).used in combination (sp) for prevention in malaria-endemic areasmonthly during pregnancy starting in the second trimesterpaired with amodiaquine for monthly administration to children for seasonal malaria chemopreventionAcute toxoplasmosisCongenital toxoplasmosistoxoplasmosis (with other agents)intermittent preventive therapy in pregnancy (IPTp)uncomplicated CQ-resistant falciparum malaria (in combination with artesunate and sulfadoxine)Treatment of falciparum malaria (only in combination with a sulfonamide or dapsone)Treatment of toxoplasmosis (in combination with sulfadoxine, first choice for immunocompromised patients)CNS toxoplasmosis (in combination with sulfadiazine and folinic acid)

Dosing

Adult: l INDICATIONS AND DOSE Visceral leishmaniasis (specialist use only) ▶ BY INTRAVENOUS INJECTION, OR BY INTRAMUSCULAR INJECTION Adult: 20 mg/kg daily for 28 days Cutaneous leishmaniasis (specialist use only) ▶ ▶ BY INTRAVENOUS INJECTION, OR BY INTRAMUSCULAR INJECTION ▶ Adult: 20 mg/kg daily for 20 days Heart disease (withdraw if conduction disturbances occur) . mucocutaneous disease .…

Pharmacokinetics

Onset

2 to 6 h

Duration

long

Half-life

85 to 100 h

Bioavailability

well absorbed

Protein binding

about 90% bound to plasma proteins

Metabolism

Metabolized

Contraindications

Pregnancy (when used in combination with sulfadoxine, due to lack of information and recommendation to avoid).
individuals with previous reactions to sulfonamides (when combined as sp)
lactating mothers
infants less than 2 months of age

Side effects

Common

occasional skin rashesreduced hematopoiesisMarrow suppressionOccasional nauseaRashesfolate deficiencyrash

Serious

megaloblastic anemia
severe cutaneous reactions
fatal cutaneous reactions
erythema multiforme
stevens-johnson syndrome
toxic epidermal necrolysis
serum sickness–type reactions
urticaria
exfoliative dermatitis
hepatitis
Megaloblastic anaemia (with higher doses, especially with marginal folate stores)
Granulocytopenia (with higher doses, especially with marginal folate stores)
Folate deficiency (rare)
seizures
severe skin reactions (toxic epidermal necrolysis, erythema multiforme, stevens-johnson syndrome)
blood dyscrasias
bone marrow suppression

Pregnancy & lactation

Pregnancy

Best avoided during pregnancy (when used in combination with sulfadoxine) until more information is available; specialist advice should be sought.

Lactation

contraindicated in lactating mothers

Drug interactions

Sulfonamides

Severe

Textbook

severe and even fatal cutaneous reactions (erythema multiforme, stevens-johnson syndrome, toxic epidermal necrolysis), serum sickness–type reactions, urticaria, exfoliative dermatitis, and hepatitis

Contraindicated for individuals with previous reactions to sulfonamides.

Source: G&G 14e · p1295

Auranofin

Severe

Database

Clinical effect not specified

Source: DDInter

Aurothioglucose

Severe

Database

Clinical effect not specified

Source: DDInter