Malarone

Atovaquone (Wellvone®, Mepron®) is a lipophilic hydroxynaphthoquinone. A related product (lapinone) was discovered 50 years ago, but at that time was abandoned since it could only be given parenterally. A fatty meal increases the absorption of atovaquone in the intestines. In the blood the molecule is highly protein bound, but there are probably no significant interactions with other protein-bound drugs. Atovaquone is eliminated by the liver and can therefore be used in renal impairment. Malarone® cannot, however, be used as prophylaxis in renal failure because the blood levels of proguanil/cycloguanil are much higher. Simultaneous use of Malarone® and rifampicin is not recommended (blood levels 50% lower). Its safety during pregnancy is not known.

Atovaquone is a powerful schizonticide for P. falciparum and P. vivax. It inhibits the mitochondria of the parasite (inhibition of the electron transport) and the de novo pyrimidine synthesis. It has a half-life of 2-3 days in adults and 1-2 days in children. On monotherapy recrudescence occurs very quickly. To avoid this problem it is combined with proguanil (brand name of the atovaquone + proguanil combination = Malarone®). These products are synergistic. The combination of atovaquone + doxycycline is also active. Absorption of Malarone® via the intestine improves if it is taken with food. The recommended curative dose is 1000 mg atovaquone + 400 mg proguanil, once daily for 3 days (adults). In practice the curative regimen for an adult is: four tablets once daily for three days. An adjusted dosage is used for children, e.g. children from 11-20 kg: 1 tablet per day for 3 days, children 21-30 kg: 2 tablets par day for 3 days, children 31-40 kg: 3 tablets per day for 3 days. Malarone is not given to children weighting less than 10kg. The combination (250 mg atovaquone + 100 mg proguanil daily) can also be used for malaria prophylaxis. The dose is then 1 tablet per day, beginning the day before travelling and then taken daily until 7 days after return. There is also a causal prophylactic effect. There is no known cross-resistance with other anti-malaria products. The first cases of Malarone resistance were reported in 2001, i.e. very soon after introduction of the drug. The product is also being studied in toxoplasmosis, babesiosis, leishmaniasis, microsporidiosis and in Pneumocystis carinii pneumonia. In the treatment of babesiosis it proved more active in some animal studies than the combination of clindamycin/quinine.

Category: Medicine Notes