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pyrimethamine (Daraprim)

Tradename: Daraprim. Indications: - treatment of toxoplasmosis in combination with a sulfonamide or clindamycin for synergy - malaria [5] - prophylaxis for malaria - used in conjunction with quinine & sulfadiazine to treatment of uncomplicated chloroquine-resistant Plasmodium falciparum - Pneumocystis pneumonia [5] - prophylaxis for pneumocystis pneumonia Dosage: 1) toxoplasmosis: a) 50-75 mg/day in combination with 1-4 g of a sulfonamide (sulfadiazine) for 1-3 weeks, then b) 25-50 mg/day for 3-5 weeks c) prophylaxis: 50 mg/week plus dapsone 50 mg QD 2) malarial prophylaxis: a) 25 mg PO weekly b) begin 1 week prior to entering endemic area c) continue at least 6-10 weeks after leaving endemic areas 3) chloroquine-resistance Plasmodium falciparum a) adults & children > 40 kg: 25 mg PO BID for 3 days b) children 20-40 kg: 25 mg PO QD for 3 days c) children 10-20 kg: 12.5 mg PO QD for 3 days d) children < 10 kg: 6.25 mg PO QD for 3 days 4) use in conjunction with folinic acid 5-10 mg/day 5) take with meals to minimize nausea/vomiting Tabs: 25 mg Pharmacokinetics: 1) well absorbed after oral administration 2) time to peak serum concentration after oral administration: 1.5-8 hours 3) protein binding 80% 4) widely distributed: Vd 2.9 L/kg; appears in breast milk 5) 1/2life is 80-95 hours 6) metabolized by the liver Adverse effects: 1) not common (1-10%) - megaloblastic anemia, leukopenia, thrombocytopenia,cagranulocytosis 2) uncommon (< 1%) - rash, insomnia, diarrhea, lightheadedness, dry mouth, fever, malaise, dermatitis, abnormal skin pigmentation, depression, seizures, pulmonary eosinophilia, atrophic glossitis 3) other - abdominal cramps Drug interactions: - sulfonamides, methotrexate, Bactrim increases folic acid deprivation & risk of bone marrow suppression Laboratory: - pyrimethamine in serum/plasma Mechanism of action: - inhibits dihydrofolate reductase in parasites Notes: - 1st generic approved Feb 2020 [6]

Interactions

drug interactions drug adverse effects of antimalarials

General

antimalarial

Properties

MISC-INFO: elimination route LIVER protein-binding 80% pregnancy-category C - safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  5. Deprecated Reference
  6. FDA News Release. Feb 28, 2020 FDA Approves First Generic of Daraprim. https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-daraprim

Component-of

pyrimethamine/sulfadiazine pyrimethamine/sulfadoxine (Fansidar, Sudox)