A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone/proguanil) for the prophylaxis of malaria in Zambia.

Abstract

Abstract. Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n ϭ 136), or one placebo tablet daily (n ϭ 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P Ͻ 0.001). The most commonly reported adverse events with at least a possible causal relationship to study medication were headache and abdominal pain, which occurred with a higher incidence in the placebo group. No subjects were withdrawn from the study due to a treatment-related adverse event. Thus, Malarone appears to have an excellent safety and efficacy profile for the chemoprophylaxis of P. falciparum infection.

Antiparasitic Agent Atovaquone

“…When A-P is taken for chemoprophylaxis for malaria, gastrointestinal side effects and headache predominate (49,74,92,114,125). In studies of the treatment of malaria with higher doses of A-P, elevations of liver transaminase and bilirubin levels are recorded in approximately 15% of treated patients (77,79).…”

“…In randomized, placebo-controlled trials, A-P demonstrated Ͼ95% protective efficacy in semi-immune adults in Kenya (113) and Zambia (125) and in children in Gabon (74).…”

An Ultraperformance LC-MS/MS Method for the Quantification of the Antimalarial Atovaquone in Plasma

“…ATQ drug concentrations may be lower if used prophylactically for prevention (10). For example, in a randomized controlled trial in which 250 mg ATQ was administered with 100 mg proguanil hydrochloride to healthy volunteers once daily, trough ATQ concentrations were 2000 ng/mL after up to 10 weeks of treatment (18). Thus, based on dosing characteristics, the low or high ATQ assay may be selected for drug quantification.…”

Malaria Chemoprophylaxis for the International Traveler, Current Options and Future Possibilities

“…Atovaquone/proquanal has demonstrated efficacy for malaria prophylaxis in areas with predominantly P. vivax (Soto et al, 2006). Atovaquone/proguanil's suppressive prophylaxis effectiveness has been shown in several clinical trials, three of which were among semi-immune populations in Gabon, Kenya, and Zambia and conducted as double-blinded, randomized, and placebo controlled trials, where overall efficacy of 98% in preventing malaria was observed in this population (Lell et al, 1998;Shanks et al, 1998;Sukwa et al, 1999;Kain et al, 2001). In two other large studies, in which non-immune travelers to malaria endemic regions were randomized to receive atovaquone/proguanil, mefloquine, or chloroquine plus proguanil, none of the patients in the atovaquone/proguanil arms who completed the study developed malaria (Hogh et al, 2000;Overbosch et al, 2001).…”