Brand Name: Malarone
Active Ingredient: atovaquone and proguanil hydrochloride
Indication: Treatment and prevention of P. falciparum malarial infection in adults and children
Company Name: Glaxo Wellcome Inc.
Availability: Approved by FDA on July 14, 2000
The antimalarial drug atovaquone was developed in the 1980s and was shown to be effective when used alone, but a recurrence of malaria was observed in some patients over time. However, when combined with proguanil, an older antimalarial drug, a 98% cure rate could be achieved.
On July 14, 2000, the FDA approved the combination of atovaquone and proguanil to prevent and treat malaria in adults and children. Produced under the trade name Malarone, the drug duo is manufactured by Glaxo Wellcome Inc., which expects Malarone to be available by mid-August 2000.
For adults using Malarone for malaria prevention, the recommended dosage is one tablet daily (250 mg atovaquone and 100 mg proguanil) starting one or two days prior to entering a malaria-endemic area, one tablet a day while in the area, and one tablet a day for only seven days after return. For children who weigh less than 88 pounds, a lower-dose pediatric tablet is available. For adult patients with acute malaria, four tablets are administered as a single dose once daily for three days. Pediatric dosages for the treatment of malaria are adjusted by body weight.
How It Works
Atovaquone and proguanil interfere with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of Plasmodium falciparum mitochondrial electron transport. Proguanil 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.
Malarone: Clinical Study Results
Clinical trials leading to U.S. approval of Malarone for prevention of malaria caused by P. falciparum involved more than 400 adults and children (children weighing at least 24 pounds) in malaria-endemic areas where subjects were treated for 10-12 weeks (refs. 1, 2). These studies showed that Malarone was 98% effective in preventing malaria. Clinical trials for the treatment of acute, uncomplicated P. falciparum malaria involved 521 adults and children (children weighing at least 24 pounds) (ref. 1). These studies showed Malarone was 98.7% effective.
What the Patient Should Know
The most common adverse events in people taking Malarone for prevention of malaria included headache and abdominal pain and occurred at rates comparable to placebo. The most common adverse events reported in over 10% of patients taking Malarone for treatment of malaria were abdominal pain, nausea, vomiting and headache in adults and vomiting in children.
Patients with severe malaria are not candidates for oral therapy. Malarone has not been evaluated for the treatment of severe malaria, including cerebral malaria.
Malarone should be taken at the same time each day with food or a milky drink.