Malarone (atovaquone; proguanil hydrochloride) Tablet

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved July 2000

Specific Treatments:

Malaria

Therapeutic Areas

General Information

Malarone is a fixed-dose combination of atovaquone and proguanil hydrochloride, antimalarial agents, in tablet formulation for prescription use only. Malarone comes in both adult and pediatric dosage tablets. The adult tablets contain 250mg of atovaquone and 100mg of proguanil hydrochloride, while the pediatric tablets contain 62.5mg of atovaquone and 25mg of proguanil hydrochloride.

Clinical 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%.

To see more clinical results for earlier studies go to Glaxo Wellcome

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

Treatment was discontinued prematurely due to side effects in only four of 436 adults. Greater occurrence of adverse effects were found with higher dosages of Malarone.

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

  • nausea
  • vomiting
  • pruritus

Treatment was discontinued prematurely due to side effects in one of 116 pediatric patients.

Malarone is contraindicated for all patients who have a history of hypersensitivity to atovaquone or proguanil hydrochloride. During clinical trials only one case of anaphylaxis was observed due to treatment with Malarone.

Patients should know that drug interactions occur with tetracycline, metoclopramide and rifampin, decreasing the effectiveness of Malarone.

While no conclusive studies have been done on humans related to pregnancy and the effects of Malarone, certain adverse effects were seen on the fetuses of rabbits and rats treated with Malarone and its components. Pregnant mothers should only take Malarone if the benefit from the drug equals or surpasses the risk to the fetus. It is also not known if Malarone is secreted in the milk of nursing mothers. Proguanil hydrochloride was found in the milk of rabbits and rats treated with the drug. It is not known if atovaquone is found in the milk of test animals treated with the drug.

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. (From FDA Label)

Additional Information

For additional information about Malarone go to: Glaxo Wellcome