pyrimethamine (Daraprim)

Introduction

Tradename: Daraprim.

Indications

• treatment of toxoplasmosis in combination with a sulfonamide or clindamycin for synergy
• malaria
  • prophylaxis for malaria
  • used in conjunction with quinine & sulfadiazine to treatment of uncomplicated chloroquine-resistant Plasmodium falciparum
• Pneumocystis pneumonia
  • prophylaxis for pneumocystis pneumonia

Dosage

• toxoplasmosis:
  • 50-75 mg/day in combination with 1-4 g of a sulfonamide (sulfadiazine) for 1-3 weeks, then
  • 25-50 mg/day for 3-5 weeks
  • prophylaxis: 50 mg/week plus dapsone 50 mg QD
• malarial prophylaxis:
  • 25 mg PO weekly
  • begin 1 week prior to entering endemic area
  • continue at least 6-10 weeks after leaving endemic areas
• chloroquine-resistance Plasmodium falciparum
  • adults & children > 40 kg: 25 mg PO BID for 3 days
  • children 20-40 kg: 25 mg PO QD for 3 days
  • children 10-20 kg: 12.5 mg PO QD for 3 days
  • children < 10 kg: 6.25 mg PO QD for 3 days
• use in conjunction with folinic acid 5-10 mg/day
• take with meals to minimize nausea/vomiting

Tabs: 25 mg

Pharmacokinetics

• well absorbed after oral administration
• time to peak serum concentration after oral administration: 1.5-8 hours
• protein binding 80%
• widely distributed: Vd 2.9 L/kg; appears in breast milk
• 1/2life is 80-95 hours
• metabolized by the liver

elimination via liver

protein binding = 80 %

Adverse effects

• not common (1-10%)
  • megaloblastic anemia, leukopenia, thrombocytopenia,cagranulocytosis
• uncommon (< 1%)
  • rash, insomnia, diarrhea, lightheadedness, dry mouth, fever, malaise, dermatitis, abnormal skin pigmentation, depression, seizures, pulmonary eosinophilia, atrophic glossitis
• other
  • abdominal cramps

• drug adverse effects of antimalarials

Drug interactions

• sulfonamides, methotrexate, Bactrim increases folic acid deprivation & risk of bone marrow suppression

• drug interaction(s) of antibiotics with warfarin

Laboratory

• pyrimethamine in serum/plasma

Mechanism of action

• inhibits dihydrofolate reductase in parasites

Notes

• 1st generic approved Feb 2020

More general terms

• antimalarial

Component of

• pyrimethamine/sulfadiazine
• pyrimethamine/sulfadoxine (Fansidar, Sudox)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4993
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=161085