Atovaquone

Atovaquone (alternative spelling: atavaquone) is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about $2.13 per standard 250 mg. tablet. It is also manufactured in the US in the liquid form, or oral suspension, under the brand name Mepron.

Atovaquone is a medication used to treat or prevent:
 * 1) Pneumocystis pneumonia (PCP), although it is not approved for treatment of severe PCP.
 * 2) Toxoplasmosis. The medication has antiparasitic and therapeutic effects.
 * 3) Malaria. It is one of the two components (along with proguanil) in the drug Malarone. Malarone has fewer side effects than mefloquine, but can be more expensive because it's taken daily.

Trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim) is generally considered first line therapy for PCP or toxoplasmosis. However, atovaquone may be used in patients who cannot tolerate, or are allergic to, TMP-SMX. In addition, atovaquone has the advantage of not causing myelosuppression, which is an important issue in patients who have undergone bone marrow transplantation.

Malaria
Atovaquone is only available as a fixed preparation with proguanil that has been commercially available from GlaxoSmithKline since 2000 as Malarone® (sometimes abbreviated A+P). It can be used both to treat and to prevent malaria.

A "standard" tablet of Malarone contains 100 mg of proguanil hydrochloride and 250 mg of atovaquone. A "pediatric" tablet of Malarone contains 25 mg of proguanil hydrochloride and 62.5 mg of atovaquone.

Treatment
The adult treatment dose is four "standard" tablets once a day for three days. In children, the drug is prescribed by body weight: Malarone is not licensed for use in children weighing 10 kg or less. The "pediatric" tablets are not used in malaria treatment.
 * 11 to 20 kg: 1 "standard" tablet once daily for 3 days;
 * 21 to 30 kg: 2 "standard" tablets once daily for 3 days;
 * 31 to 40 kg: 3 "standard" tablets once daily for 3 days;
 * 41 kg and above: use adult dose.

The advice of a specialist should always be sought when starting malaria treatment. Malarone should not be used to treat severe malaria, when an injectable drug (quinine or artesunate in the UK; quinidine in the US) should be used instead.

Prevention
Medical advice should always be taken before choosing a drug for malaria prevention. Because some strains of malaria are resistant, Malarone is not effective for malaria prevention in all parts of the world. It must be taken with a fatty meal or at least some milk to be absorbed adequately.

The adult dose is one "standard" tablet daily starting one or two days before traveling into a malaria-endemic area, and continuing throughout the stay and then for another 7 days after returning from the malarious area.

The child dose is prescribed according to body weight: The duration of treatment is the same as for adults.
 * 11–20 kg: 1 "pediatric" tablet once daily;
 * 21–30 kg: 2 "pediatric" tablets once daily;
 * 31–40 kg: 3 "pediatric" tablets once daily;
 * 41 kg and above use adult dose.

Resistance
Proguanil acts as a mitochondrial sensitiser and synergizes with atovaquone; also, there is a high natural frequency of cytochrome B mutants which leads to a high failure rate if atovaquone is used on its own to treat malaria. Specific mutations (Y268S, Y268C) have been shown to confer resistance in vivo,  but there are other mechanisms of resistance that remain unknown.