title: Atovaquone/proguanil: a review of its use for the prophylaxis of Plasmodium falciparum malaria.
abstract: 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).
  
  
  CONCLUSIONS
  Atovaquone/proguanil is a fixed-dose combination antimalarial tablet that provides effective prophylaxis of P. falciparum malaria, including drug-resistant strains. Both atovaquone and proguanil are effective against hepatic stages of P. falciparum, which means that treatment need only continue for 7 days after leaving a malaria-endemic region. Atovaquone/proguanil was generally well tolerated and was associated with fewer gastrointestinal adverse events than chloroquine plus proguanil, and fewer neuropsychiatric adverse events than mefloquine. Thus, atovaquone/proguanil provides effective prophylaxis of P. falciparum malaria and compared with other commonly used antimalarial agents has an improved tolerability profile, and, overall, a more convenient dosage regimen, particularly in the post-travel period.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: Kate
authors.initials: K
authors.lastname: McKeage
authors.forename: Lesley
authors.initials: L
authors.lastname: Scott
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control*; D009285:Naphthoquinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002727:Proguanil / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014195:Travel
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D009285:Naphthoquinones; D002727:Proguanil; D053626:Atovaquone