Atovaquone/proguanil, sold under the trade names Malarone among others, is a combination of two antimalarial medication atovaquone and proguanil. It is used to treat and prevent malaria, including chloroquine-resistant malaria. It is not recommended for severe or complicated malaria. It is taken by mouth.
|Trade names||Malarone, Malanil, others|
Common side effects include abdominal pain, vomiting, diarrhea, cough, and itchiness. Serious side effects may include anaphylaxis, Stevens-Johnson syndrome, hallucinations, and liver problems. It is unclear if use during pregnancy or breastfeeding is safe for the baby. It is not recommended to prevent malaria in those with poor kidney function. Atovaquone works by interfering with the function of mitochondria in malaria while proguanil by blocking dihydrofolate reductase.
Atovaquone/proguanil was approved for medical use in the United States in 2000. It has been available as a generic medication since 2011. In the United Kingdom it costs £2.10 per dose as of 2019. The wholesale cost in the United States is $US 2.82 per dose as of 2019.
The adult treatment dose is four standard tablets once a day for three days. In children, the drug is prescribed by body weight:
- 11 to 20 kg: 1 standard tablet once daily for 3 days;
- 21 to 30 kg: 2 standard tablets once daily for 3 days;
- 31 to 40 kg: 3 standard tablets once daily for 3 days;
- 41 kg and above: use adult dose.
Atovaquone/proguanil is not licensed for use in children weighing 10 kg or less. The pediatric tablets are not used in malaria treatment, but are used for prophylaxis.
Atovaquone/proguanil is not normally used to treat severe malaria, when an injectable drug such as quinine is used instead.
Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil frequently causes if taken without food. Also, stomach irritation may occur if one lies down within a half hour after taking this medicine.
The adult dose is one standard tablet daily starting one or two days before traveling into a malaria-endemic area, and continuing throughout the stay and then for another seven days after returning from the area.
The child dose is prescribed according to body weight:
- 11–20 kg: 1 pediatric tablet once daily;
- 21–30 kg: 2 pediatric tablets once daily;
- 31–40 kg: 3 pediatric tablets once daily;
- 41 kg and above use adult dose.
The duration of treatment is the same as for adults.
Proguanil acts as a mitochondrial sensitiser and synergizes with atovaquone. When atovaquone is used as a sole agent, a high natural frequency of cytochrome b mutants leads to a high failure rate. This is potentially due to the high lipophilicity and slow uptake of atovaquone, which results in a relatively prolonged period of parasite exposure at ineffective concentrations. Specific mutations (Y268S, Y268C) have been shown to confer resistance in vivo, but the other mechanisms of resistance remain unknown.
Side effects are generally mild. While some people experience side effects, such as coughing, diarrhea, dizziness, headache, loss of appetite, mouth sores, nausea, stomach pain, vomiting, or weakness, the majority have none or few of these.
Mechanism of action
Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasitic electron transport chain, collapsing the mitochondrial membrane potential. The malarial electron transport chain does not contribute significantly to ATP synthesis; thus, it is believed that parasite death is due to the indirect inhibition of dihydroorotate dehydrogenase, which requires transport chain function and is essential to pyrimidine biosynthesis.
A standard tablet of Malarone contains 100 mg of proguanil hydrochloride and 250 mg of atovaquone. A pediatric tablet contains 25 mg of proguanil hydrochloride and 62.5 mg of atovaquone.
Glaxo Wellcome patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013. The U.S. Food and Drug Administration (FDA) approved a generic formulation from Glenmark Generics in 2011. In February 2013, the United Kingdom High Court revoked Glaxo's patent on grounds of obviousness, which clears the way for firms to sell generic versions there.
- Glaxo Smith Kline monograph on MALARONE
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- Generic Malarone Availability
- Drug Details
- Atovaquone Proguanil (Malarone) Patent Revoked & Glenmark Launches First UK Generic