Atovaquone/proguanil is a fixed-dose combination
tablet of two
antimalarial agents and is highly effective for the prevention of
Plasmodium falciparum malaria. In combination with
proguanil, the ability of
atovaquone to inhibit parasitic mitochondrial electron transport is markedly enhanced. Both
atovaquone and
proguanil are active against hepatic (pre-erythrocytic) stages of P. falciparum, thereby providing causal prophylaxis and eliminating the need to continue post-travel treatment beyond 7 days. Both agents are also active against erythrocytic stages of P. falciparum, thereby providing suppressive prophylaxis.
Atovaquone/proguanil is highly effective against
drug-resistant strains of P. falciparum, and cross-resistance has not been observed between
atovaquone and other
antimalarial agents. In comparative, randomised clinical trials, there were no cases of P.
falciparum malaria in nonimmune adults, adolescents and children (>/=11 kg) visiting
malaria-endemic regions for </=28 days and receiving
atovaquone/proguanil (250/100 mg in adults and dosage based on bodyweight in children <40 kg) once daily. The efficacy for the prevention of P.
falciparum malaria was estimated at 100% for
atovaquone/proguanil and for
mefloquine, and 70% for
chloroquine plus
proguanil. In individuals (>/=11 kg) from endemic regions who may carry some immunity to
malaria (semi-immune), the prophylactic efficacy rating for
atovaquone/proguanil based on placebo-controlled trials was 95-100%.
Atovaquone/proguanil is generally well tolerated by both adults and children. The most common treatment-related adverse events in placebo-controlled trials were
headache and
abdominal pain, which occurred at a rate similar to that observed with placebo.
Atovaquone/proguanil therapy was associated with significantly fewer gastrointestinal adverse events than
chloroquine plus
proguanil, and significantly fewer neuropsychiatric adverse events than
mefloquine in nonimmune individuals. Significantly fewer recipients of
atovaquone/proguanil discontinued treatment because of adverse events than individuals receiving
chloroquine plus
proguanil or
mefloquine (p < 0.05).
CONCLUSION: