Atovaquone

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Atovaquone
Systematic (IUPAC) name
3-[4-(4-chlorophenyl)cyclohexyl]- 4-hydroxy-naphthalene-1,2-dione
Identifiers
CAS number	95233-18-4
ATC code	P01AX06
PubChem	74989
DrugBank	APRD00805
Chemical data
Formula	C22H19ClO3
Mol. weight	366.837 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	2.2 to 3.2 days
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	PoM (UK), Rx [US]
Routes	oral only

Atovaquone 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.

Atovaquone is a medication used to treat or prevent:

1. Pneumocystis carinii 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. (Source)^[1]

Trimotheoprim-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.

Contents 1 Malaria 1.1 Treatment 1.2 Prevention 1.3 Resistance 2 See also 3 References

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

[edit] Treatment

The adult treatment dose is four "standard" tablets once a day for three days. In children, the drug is prescribed by body weight:

• 11 to 20kg: 1 "standard" tablet once daily for 3 days;
• 21 to 30kg: 2 "standard" tablets once daily for 3 days;
• 31 to 40kg: 3 "standard" tablets once daily for 3 days;
• 41kg and above: use adult dose.

Malarone is not licensed for use in children weighing 10kg or less. The "pediatric" tablets are not used in malaria treatment.

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 artemesinin in the UK; quinidine in the US) should be used instead.

[edit] Prevention

Medical advice should always be taken before choosing a drug for malaria prevention. Malarone is not effective for malaria prevention in all parts of the world.

The adult dose is one "standard" tablet daily starting one or two days before travelling, and continuing for one week after returning from the malarious area.

The child dose is prescribed according to body weight:

• 11–20kg: 1 "pediatric" tablet once daily;
• 21–30kg: 2 "pediatric" tablets once daily;
• 31–40kg: 3 "pediatric" tablets once daily;
• 41kg and above use adult dose.

The duration of treatment is the same as for adults.

[edit] 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,^[2][3][4] but there are other mechanisms of resistance that remain unknown.^[5]

[edit] See also

• Molecular Basis for Atovaquone Resistance in Pneumocystis jirovecii
• Atovaquone (Meprone)
• British National Formulary

[edit] References

1. ^ (Source)
2. ^ Färnet A, Lindberg J, Gil P, et al. (2003). "Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguoanil hydrochloride: case reports". Brit Med J 326: 628–29.
3. ^ Fivelman QL, Butcher GA, Adagu IS, et al. (2002). "Malarone treatment failure and in-vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria". Malaria J 1: 1.
4. ^ Schwartz E, Bujanover S, Kain KC (2003). "Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveller to east Africa". Clin Infect Dis 37: 450–51.
5. ^ Wichmann O, Muehlen M, Gruss H, et al. (2004). "Malarone treatment failure not associated with previously described mutations in the cytochrome b gene". Malaria J 3: 14.