Pyrimethamine+ sulfadoxine, prevention

In an open prospective study in 95 HIV-infected patients with successfully treated Pneumocystis proved pneumonia, pyrimethamine + sulfadoxine (25/500 mg) was given twice weekly to prevent relapse (159). There were allergic skin reactions in 16 patients, resulting in permanent withdrawal in six. Two patients developed serious adverse reactions (Stevens-Johnson syndrome), both of whom had continued to take prophylaxis despite progressive hypersensitivity reactions. 

Schurmann D, Bergmann F, Albrecht H, Padberg J, Grunewald T, Behnsch M, Grobusch M, Vallee M, Wunsche T, Ruf B, Suttorp N. Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS. J Infect 2001 42(1) 8-15. 

Chloroquine-resistant P falciparum is endemic in many regions of Africa, including Kenya, and the prophylactic use of chloroquine as a sole agent will not prevent infection. While pyrimethamine-sulfadoxine has been used prophylactically. it is not the drug of choice. Weekly doses of mefloquine one week before entering an endemic area, during the sojourn, and for 4 weeks after leaving, is the preferred method. 

A study in patients with AIDS found that zidovudine 250 mg four times daily did not adversely affeet the prevention of toxoplasma eneephalitis with pyrimethamine/sulfadoxine (Fansidar), one tablet twice weekly for up to 8 months. /w vitro and animal data have shown that the combination of zidovudine and pyrimethamine caused synergistic decreases in lymphocyte and neutrophil numbers. ... 

Sulfadoxine-pyrimethamine (Fansidar) Folate antagonist combination Treatment of infections with some chloroquine-resistant P falciparum, including combination with artesunate intermittent preventive therapy in endemic areas... 

In many areas, resistance to folate antagonists and sulfonamides is common for P falciparum and less common for P vlvax. Resistance is due primarily to mutations in dihydrofolate reductase and dihydropteroate synthase, with increasing numbers of mutations leading to increasing levels of resistance. At present, resistance seriously limits the efficacy of sulfadoxine-pyrimethamine (Fansidar) for the treatment of malaria in most areas, but in Africa most parasites exhibit only moderate resistance, such that antifolates appear to continue to offer preventive efficacy against malaria. Because different mutations may mediate resistance to different agents, cross-resistance is not uniformly seen. 

In addition, sulfadoxine and pyrimethamine (Fansidar) are indicated in prophylaxis of malaria in individuals traveling to areas where chloroquine-resistant P. falciparum malaria is endemic. However, resistant strains may be encountered. Regardless of the prophylactic regimen used, it is still possible to contract malaria. Moreover, this combination has been used as a prophylactic agent in the prevention of Pneumocystis carinii pneumonia in patients with AIDS. 

Sulfadoxine (1500 mg) and pyrimethamine (75 mg) orally as a single dosage is indicated for the treatment of P. falciparum malaria in patients in whom chloroquine resistance is suspected. However, chloroquine remains the drug of choice for travelers to malarious areas, hi addition, sulfadoxine-pyrimethamine has been used as a prophylactic agent for the prevention of Pneumocystis carinii pneumonia in patients with AIDS, usually as a second-tine agent. 

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