[e-drug] Effectiveness and safety of atovaquone-proguanil prophylaxis

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: Effectiveness and safety of atovaquone-proguanil prophylaxis
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Nakato H, Vivancos R, Hunter PR. A systematic review and meta-analysis
of the effectiveness and safety of atovaquone proguanil (Malarone) for
chemoprophylaxis against malaria. J Antimicrob Chemother. 2007
Nov;60(5):929-36. Epub 2007 Sep 10

School of Medicine, Health Policy and Practice, University of East
Anglia, Norwich NR4 7TJ, UK.

Objectives. A systematic review and meta-analysis of the effectiveness
of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against
malaria.

Methods. The data sources searched for this study included Cochrane
systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of
Knowledge and Annals of Tropical Medicine. All unconfounded randomized
controlled trials assessing the chemoprophylaxis against malaria with
atovaquone-proguanil were included in the review. Data on study design,
study sample, inclusion and exclusion criteria, allocation, blinding,
primary and secondary study end points were all extracted by one
reviewer and independently rechecked by the second reviewer. 
Results. In general, all 10 studies identified had excellent quality
with total scores of >/=4 using the Jadad criteria. Ten controlled
trials comprising 4539 participants were included for this review. A
meta-analysis of six of the ten studies found chemoprophylaxis with
atovaquone-proguanil, with a prophylaxis efficacy of 95.8% (95% CI =
91.5-97.9), to be superior to placebo. It was also considered safe and
better tolerated with fewer treatment-related adverse events that could
lead to premature discontinuation of prophylaxis than in controls.
Comparison with alternative chemoprophylaxis also showed
atovaquone-proguanil to be better tolerated with fewer treatment-related
self-reported adverse events (RR = 0.8234; 95% CI = 0.673164-1.01) or
severe adverse events (RR = 0.6140; 95% CI = 0.420055-0.8975).
Atovaquone-proguanil is well tolerated with no difference in
non-compliance with placebo (RR = 0.8804; 95% CI = 0.6964-1.113; I(2) =
31.4%). 

Conclusions. Evidence from this review shows that atovaquone-proguanil
is highly efficacious as a prophylactic agent against malaria infection
and is very well tolerated compared with other antimalarial agents.