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INDICATIONS

• 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

*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 <100–200.
• 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

ADVERSE DRUG REACTIONS

• 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 50–100 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.

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

DRUG INTERACTIONS

• TMP/SMX, dapsone, ganciclovir, AZT, and interferon: Potential for additive bone marrow suppression.
• Lorazepam: May increase risk of hepatotoxicity

SPECTRUM

PHARMACOLOGY

Pharmacology

COMMENTS

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.
  
  

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Dapsone
• Pregnancy and perinatal transmission (Zambia specific)
• Sulfadiazine
• Toxoplasmosis
• leucovorin