Pyrimethamine adverse effects

INTERFERON ZIDOVUDINE t adverse effects with zidovudine Additive toxicity Monitor FBC and renal function closely. 1 doses as necessary. Use of pyrimethamine as prophylaxis seems to be tolerated... 

PYRIMETHAMINE H2 RECEPTOR BLOCKERS -CIMETIDINE t efficacy and adverse effects of antimalarials Inhibition of metabolism, some definitely via CYP3A4 Avoid co-administration... 

Two other agents show promise in treatment of ocular toxoplasmosis. Atovaquone, primarily used for mild to moderate episodes of Pneumocystis carinii pneumonia, has been effective in small series of patients with toxoplasmosis. It appears to have activity against both tachy-zoites and tissue cysts. More recent studies on atovaquone in toxoplasmosis are limited to murine models, and no further reports on this drug therapy in humans have been published. Azithromycin, a macrolide antibiotic, is efficacious against T. gondii and can also kill tissue cysts. A randomized study of 46 patients compared the combinations of azithromycin plus pyrimethamine versus pyrimethamine plus sulfadiazine in treatment of ocular toxoplasmosis efficacy was similar, but the azithromycin/ pyrimethamine regimen caused less adverse effects. 

The chemotherapeutic response of Plasmodium berghei to various combinations of mefloquine with other drugs (sulfadoxine + pyrimethamine, primaquine, floxacrine) have shown that the desired effects are purely additive (SEDA-13, 809), so the adverse effects too are probably only those of the individual compounds. Adverse reactions occurred in 46% of 400 patients treated with Fanimef (mefloquine + pyrimethamine + sulfadoxine) (SEDA-12, 693). Of note were dizziness (29%), nausea (9.5%), vomiting (7.3%), weakness/lassitude (5.8%), abdominal discomfort or pain (5.5%), diarrhea (3.8%), pruritus (3.0%), insomnia (2.0%), and headache (2.0%). 

In a prospective, randomized, open, multicenter trial of pyrimethamine -I- azithromycin versus pyrimethamine + snlfadiazine for the treatment of ocular toxoplasmosis in 46 patients with sight-threatening ocular toxoplasmosis, the two regimens had similar efficacy however, the adverse effects were significantly less common and severe with pyrimethamine + azithromycin (2). 

Pyrimethamine 50 mg/day has been nsed in combination with clindamycin for the treatment of Toxoplasma encephalitis in AIDS. Adverse effects were common (rash, diarrhea, nansea), bnt the incidence of hematological reactions was lower than with the combination of snlfadiazine and pyrimethamine (SEDA-16, 309). 

Pyrimethamine (25 mg), sulfadoxine (500 mg), and mefloquine (250 mg) are available in the combination formulation known as Fansimef. The adverse effects characteristic of aU three components can be expected. 

The hematological adverse effects of the combination of pyrimethamine plus sulfadoxine are largely those known from pyrimethamine, that is leukopenia, agranulocytosis, thrombocytopenia, and pancytopenia, but the literature gives the impression that when using this combination these effects are more marked, with lower cell counts (5). 

Intermittent iron supplementation with pyrimethamine + sulfadoxine has been investigated in 328 anemic but symptom-free Kenyan children, who were randomly given either iron (ferrous fumarate suspension 6.25 g/1 twice a week) or placebo and pyrimethamine + sulfadoxine (25 mg and 1.25 mg/kg once every 4 weeks) or placebo (82 in each group) (6). After 12 weeks, those who took iron and pyrimethamine + sulfadoxine, iron alone, or pyrimethamine + sulfadoxine alone had higher hemoglobin concentrations than those who took the double placebo. No adverse effects were reported. 

Hyperpigmentation is a very rare adverse effect of pyrimethamine. 

Pyrimethamine is an inhibitor of dihydrofolate reductase and causes tetrahydrofolate deficiency. It is teratogenic in animals in rats it produces limb defects, cleft palate, and brachygnathia, and in chick embryos micromelia. Fetal death has been seen in rats and hamsters. However, in toxoplasmosis, pyrimethamine, with or without a sulfonamide, has been given to pregnant women without evidence of subsequent abnormalities. Supplementation with folic acid has been advocated to prevent or reduce adverse effects (SEDA-13,812), but it is not known if this could impair efficacy. 

WR-243251 is a floxacrine analogue, a dihydroacridine-dione. It is active in vitro against chloroquine-resistant, mefloquine-resistant, and pyrimethamine-resistant strains of malaria (1). By analogy to quinacrine and floxacrine, there is concern about possible dermatological, cardiac, and neuropsychiatric toxicity and vascular adverse effects. 

Artemether raises pyrimethamine piasma levels, but this does not appear to cause an increase in adverse effects. 

Observational studies During a surveillance period of 2 years, 1552 patients with uncomplicated P. falciparum malaria who had received sulfadoxine 4- pyrimethamine with artesunate on the Northern coast of Peru were followed up 8.8% reported at least one adverse effect, the most common being vomiting, nausea, headache, abdominal pain, dizziness, and fever there were no severe adverse effects [13 ]. 

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