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Atovaquone/Proguanil (By mouth)

Treats and prevents malaria.

What works?

Learn more about the effects of these drugs. The most reliable research is summed up for you in our featured article.

Brand names include
Malarone, Malarone Pediatric
Other forms
Oral route
Drug classes About this
Ubiquinone/Biguanide Combination

What works? Research summarized

Evidence reviews

Atovaquone‐proguanil appears to be more effective than individual drugs for treating uncomplicated malaria, but there are few data comparing atovaquone‐proguanil to other combination therapies

Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. This can be reduced by treating people with combination drugs such as atovaquone‐proguanil. The review found 10 trials, most of low methodological quality and most funded by a single pharmaceutical company. In addition, trials were small and had few participants thus evidence suggesting atovaquone‐proguanil as more effective than a number of single drug treatments at eliminating the Plasmodium falciparum malaria parasite from the blood was limited. There were few good quality data comparing atovaquone‐proguanil with other new combination therapies. There were not enough data to assess adverse events, but all trials recorded some adverse events.

A systematic review and meta-analysis of the effectiveness and safety of atovaquone-proguanil (Malarone) for chemoprophylaxis against malaria

The authors concluded that atovaquone-proguanil (Malarone) is a highly effective agent for malaria prophylaxis, which is well tolerated compared with other antimalarials. This was a generally well-conducted review and, despite considerable clinical differences between the studies, the conclusions are likely to be reliable.

Azithromycin is not useful as monotherapy for uncomplicated malaria. In combinations with other antimalarials, it may need to be used at high doses, potentially affecting tolerability.

To help prevent the malaria parasite from developing resistance to antimalarial medicines, the WHO recommends the use of combination therapy, where malaria infections are treated with more than one drug simultaneously. As azithromycin is an antibiotic that also has an effect on the malaria parasite, we assessed its efficacy and tolerability as an antimalarial when used alone or as part of combination therapy with other antimalarials. Our review of studies conducted over the past 14 years suggests that azithromycin is a relatively weak antimalarial whose efficacy depends on the drug dose and the partner drug in the combination therapy. The data suggest that, among adults, the higher doses needed to achieve an acceptable level of treatment success with malaria may be less well tolerated. Unless the ongoing product and dose optimisation process results in a universally efficacious product or identifies a specific niche application that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future as an antimalarial does not look promising.

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Summaries for consumers

Atovaquone‐proguanil appears to be more effective than individual drugs for treating uncomplicated malaria, but there are few data comparing atovaquone‐proguanil to other combination therapies

Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. This can be reduced by treating people with combination drugs such as atovaquone‐proguanil. The review found 10 trials, most of low methodological quality and most funded by a single pharmaceutical company. In addition, trials were small and had few participants thus evidence suggesting atovaquone‐proguanil as more effective than a number of single drug treatments at eliminating the Plasmodium falciparum malaria parasite from the blood was limited. There were few good quality data comparing atovaquone‐proguanil with other new combination therapies. There were not enough data to assess adverse events, but all trials recorded some adverse events.

Azithromycin is not useful as monotherapy for uncomplicated malaria. In combinations with other antimalarials, it may need to be used at high doses, potentially affecting tolerability.

To help prevent the malaria parasite from developing resistance to antimalarial medicines, the WHO recommends the use of combination therapy, where malaria infections are treated with more than one drug simultaneously. As azithromycin is an antibiotic that also has an effect on the malaria parasite, we assessed its efficacy and tolerability as an antimalarial when used alone or as part of combination therapy with other antimalarials. Our review of studies conducted over the past 14 years suggests that azithromycin is a relatively weak antimalarial whose efficacy depends on the drug dose and the partner drug in the combination therapy. The data suggest that, among adults, the higher doses needed to achieve an acceptable level of treatment success with malaria may be less well tolerated. Unless the ongoing product and dose optimisation process results in a universally efficacious product or identifies a specific niche application that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future as an antimalarial does not look promising.

Reliable research about the benefits and harms of treatments for malaria in pregnant women is scarce

Women are more vulnerable to malaria during pregnancy, and malaria may have harmful effects on the baby. Treatment options are becoming more limited because the malaria parasite is developing resistance to existing drugs and due to concerns about whether drugs may harm the baby. Evidence from randomized controlled trials is limited, with few drugs and drug combinations being evaluated.

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