General Information

Malarone is a fixed-dose combination of atovaquone and proguanil hydrochloride, antimalarial agents.

Malarone is specifically indicated for:

• prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported
• treatment of acute, uncomplicated P. falciparum malaria

Malarone is supplied as tablets. The daily dose should be taken at the same time each day with food or a milky drink. In the event of vomiting within 1 hour after dosing, a repeat dose should be taken. Malarone may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets.

Prevention of Malaria

Start prophylactic treatment with Malarone 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return.

• Adults: One Malarone tablet (adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day.
• Pediatric Patients: The dosage for prevention of malaria in pediatric patients is based upon body weight seen below:

Treatment of Acute Malaria

• Adults: Four Malarone tablets (adult strength; total daily dose 1 g atovaquone/400 mg proguanil hydrochloride) as a single daily dose for 3 consecutive days.
• Pediatric Patients: The dosage for treatment of acute malaria in pediatric patients is based upon body weight seen below:

Mechanism of Action

The constituents of Malarone, atovaquone and proguanil hydrochloride, interfere with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis.

Side Effects

Side effects which may occur in adult patients include, but are not limited to:

• abdominal pain
• nausea
• vomiting
• headache
• diarrhea
• asthenia
• dizziness
• anorexia

Side effects which may occur in pediatric patients include, but are not limited to:

• nausea
• vomiting
• pruritus

Clinical Trial Results

Three phase II clinical studies were conducted, one testing atovaquone alone, one testing proguanil hydrochloride alone and one testing the combination, for the treatment of acute, uncomplicated malaria. Malarone was tested in eight phase III controlled clinical trials for the same indication. 471 patients were treated with the equivalent of four Malarone tablets once daily for three days. 464 had a sensitive response (the elimination of parasitemia with no recurrent sign of parasitemia for up to 28 days) and seven patients had R1 resistance (the elimination of parasitemia, but with recurrence between 7 and 28 days following treatment). Treatment with Malarone was comparable with treatment with a comparator drug in four of the studies and better than treatment with a comparator drug in the other four studies. The overall efficacy in 521 patients was 98.7%.