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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Pyrimethamine

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
12-01-2010

Zambia Specific Information

  • Available formulation in Zambia: 25 mg tablet 
  • Due to additive bone marrow suppression, co-administer AZT with caution or use other NRTI.
  • First line treatment of CNS toxoplasmosis: pyrimethamine + sulfadiazine (plus folinic acid)
Zambia Information Author: Paul A. Pham, Pharm.D.

INDICATIONS

FDA

  • Malaria (acute) in combination with sulfadoxine and quinine in treatment of chloroquine-resistant Plasmodium falciparum malaria. Resistance prevalent worldwide; not recommended as prophylactic agent for travelers to most areas.
  • Toxoplasmosis (in combination with sulfadiazine or clindamycin plus leucovorin).

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Daraprim PyrimethamineGlaxoSmithKlineoral
tablet
25 mg
$0.58
Fansidar Pyrimethamine/sulfadoxineRocheoral
tablet
Pyrimethamine 25 mg + sulfadoxine 500 mg
$4.14

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • CNS toxoplasmosis, induction therapy: 200 mg x1, then 50-75 mg once-daily (+ folinic acid 10-20 mg/d + sulfadiazine 1.5 gm q6h or clindamycin 600 mg IV q6h) x >6 wks.
  • CNS toxoplasmosis, maintenance therapy: 25-50 mg (+ folinic acid 15 mg + sulfadiazine 0.5-1 gm q6h or clindamycin 300-450 mg q6h) until immune reconstitution (CD4 >200 x 6 mos, induction therapy completed, and asymptomatic). Reintroduced maintenance therapy if CD4 count decreases to <200.
  • Toxoplasmosis prophylaxis: 50 mg/wk (+ folinic acid 25 mg/wk + dapsone 50-100 mg once-daily + leucovorin 25 mg/wk OR atovaquone 1500 mg/d +/- pyrimethamine 25 mg/d + leucovorin 10 mg/d). Note: TMP/SMX 1 DS daily preferred.
  • Toxoplasmosis primary prophylaxis can be discontinued in pts who have responded to ART with increase in CD4 count to >200 for >3 mos, but should be reintroduced if CD4 decreases to <100â??200.
  • Malaria prophylaxis: Fansidar 1 tab (pyrimethamine 25 mg/sulfadoxine 500 mg) weekly or OR 2 tabs every other week; start 1 to 2 days before arrival in endemic area and continue during stay and for 4 to 6 wk after leaving endemic area. Generally not recommended due to high incidence of rash.
  • Acute malaria, acute: Fansidar 2 to 3 tabs (pyrimethamine 50-75 mg/sufadoxine 1000-1500 mg) as single dose.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose; HD: no data, usual dose likely. dose post-HD on days of HD.

DOSING IN HEMODIALYSIS

No data, usual dose likely (dose post-HD on days of HD).

DOSING IN PERITONEAL DIALYSIS

47% removed after PD.

DOSING IN HEMOFILTRATION

No data. Usual dose likely.

ADVERSE DRUG REACTIONS

OCCASIONAL

  • Reversible pancytopenia (megaloblastic anemia, leucopenia, agranulocytosis, and thrombocytopenia) secondary to depletion of folic acid stores. Generally prevented with co-administration of leucovorin. Consider increasing leucovorin dose to 50â??100 mg/day if hematologic toxicity observed.
  • GI intolerance: abdominal pain and vomiting (improved by administration with meals).
  • Headache, dizziness, and insomnia.
  • With sulfonamide co-administration: rash, hepatitis.
RARE

  • Neurologic: tremors, ataxia, and seizure.
  • With sulfonamide co-administration: Stevens-Johnson syndrome, TEN, erythema multiforme and anaphylaxis can occur.

DRUG INTERACTIONS

SPECTRUM

P. falciparum, T. gondii

PHARMACOLOGY

Pharmacology

COMMENTS

Treatment of choice (with sulfadiazine and leucovorin) for CNS toxoplasmosis. Fansidar (pyrimethamine/sulfadoxine) is not first -line agent for malaria prophylaxis due to high incidence of rash and availability of better tolerated alternatives (e.g. atovaquone/proguanil, mefloquine, and doxycycline).

Basis for Recommendations

  • National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) ; Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents ; http://AIDSinfo.nih.gov/ ; 2008 ; Vol.
    Rating: Basis for recommendation
    Comments:Initial therapy of choice for CNS toxoplasmosis is pyrimethamine + sulfadiazine + leucovorin.

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