Atovaquone/proguanil

Malarone_tablets.jpg

Atovaquone/proguanil is a combination medication used for the treatment and prevention of malaria. It consists of two active ingredients: atovaquone and proguanil. This combination is marketed under the brand name Malarone among others.

Medical Uses

Atovaquone/proguanil is primarily used for:

• Malaria prophylaxis: It is taken to prevent malaria, especially in travelers to areas where malaria is prevalent.
• Malaria treatment: It is used to treat uncomplicated malaria caused by Plasmodium falciparum, a parasite known for its resistance to other antimalarial drugs.

Mechanism of Action

The two components of atovaquone/proguanil work synergistically to inhibit the growth of the malaria parasite:

• Atovaquone interferes with the parasite's mitochondrial electron transport chain, which is essential for energy production.
• Proguanil is a prodrug that is converted into its active form, cycloguanil, which inhibits the enzyme dihydrofolate reductase (DHFR), disrupting the parasite's ability to synthesize DNA and replicate.

Dosage and Administration

The dosage of atovaquone/proguanil varies depending on whether it is being used for prevention or treatment:

• For malaria prophylaxis, it is typically taken once daily, starting 1-2 days before entering a malaria-endemic area, continuing throughout the stay, and for 7 days after leaving the area.
• For malaria treatment, it is usually taken as a three-day course, with one dose taken daily.

Side Effects

Common side effects of atovaquone/proguanil include:

• Nausea
• Vomiting
• Abdominal pain
• Headache
• Diarrhea

Serious side effects are rare but can include:

• Severe allergic reactions
• Hepatotoxicity
• Anemia

Contraindications

Atovaquone/proguanil should not be used in individuals with:

• Severe renal impairment
• Known hypersensitivity to atovaquone, proguanil, or any component of the formulation

Interactions

Atovaquone/proguanil may interact with other medications, including:

• Rifampin and rifabutin, which can reduce the effectiveness of atovaquone.
• Tetracycline, which can also reduce the effectiveness of atovaquone.
• Metoclopramide, which can decrease the absorption of atovaquone.

Pharmacokinetics

• Atovaquone has a half-life of approximately 2-3 days and is primarily excreted unchanged in the feces.
• Proguanil has a half-life of about 12-21 hours and is metabolized in the liver to its active form, cycloguanil.

History

Atovaquone/proguanil was approved for medical use in the late 1990s and has since become a widely used option for both the prevention and treatment of malaria.

See Also

• Malaria
• Antimalarial medication
• Plasmodium falciparum
• Prophylaxis