Atovaquone
2869000
221290012
2008-06-23T21:44:59Z
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{{drugbox
| IUPAC_name = 2-[4-(4-chlorophenyl)cyclohexyl]- 3-hydroxynaphthalene-1,4-dione
| image = Atovaquone structure.svg
| CAS_number = 95233-18-4
| ATC_prefix = P01
| ATC_suffix = AX06
| ATC_supplemental =
| PubChem = 74989
| DrugBank = APRD00805
| C=22 | H=19 | Cl=1 | O=3
| molecular_weight = 366.837 g/mol
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 2.2 to 3.2 days
| pregnancy_category =
| legal_status = PoM (UK), Rx [US]
| routes_of_administration = oral only
}}
[[Image:Malarone tablets.jpg|270px|right|thumb|Malarone anti-malaria tablets, as issued in the UK.]]
'''Atovaquone''' (alternative spelling: '''atavaquone''') is a chemical compound that belongs to the class of [[naphthalene]]s. 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.<ref>[http://www.aegis.com/pubs/atn/1992/ATN16401.html (ATN) Atovaquone (Mepron; 566C80) Approved for Pneumocystis; Drug Development, Activism Success]</ref> It is also manufactured in the US in the liquid form, or oral suspension, under the brand name Mepron.<ref>[http://www.drugs.com/pro/mepron.html Mepron]</ref>
Atovaquone is a medication used to treat or prevent:
# [[Pneumocystis pneumonia]] (PCP), although it is not approved for treatment of severe PCP.
# [[Toxoplasmosis]]. The medication has antiparasitic and therapeutic effects.
# [[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.<ref>[http://healthlink.mcw.edu/article/979237802.html Malarone: New Malaria Medication With Fewer Side-effects]</ref>
[[Co-trimoxazole|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:
*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.
Malarone is not licensed for use in children weighing 10 kg 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 [[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:
*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.
The duration of treatment is the same as for adults.
===Resistance===
Proguanil acts as a [[mitochondrion|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,''<ref>{{cite journal | author=Färnet A, Lindberg J, Gil P, ''et al.'' | title=Evidence of ''Plasmodium falciparum'' malaria resistant to atovaquone and proguoanil hydrochloride: case reports | year=2003 | journal=Brit Med J | volume=326 | pages=628–29 | doi=10.1136/bmj.326.7390.628 | pmid=12649236 }}</ref><ref>{{cite journal | author=Fivelman QL, Butcher GA, Adagu IS, ''et al.'' | title=Malarone treatment failure and in-vitro confirmation of resistance of ''Plasmodium falciparum'' isolate from Lagos, Nigeria | year=2002 | journal=Malaria J | volume=1 | pages=1 | doi=10.1186/1475-2875-1-1 }}</ref><ref>{{cite journal | author=Schwartz E, Bujanover S, Kain KC | title=Genetic confirmation of atovaquone-proguanil-resistant ''Plasmodium falciparum'' malaria acquired by a nonimmune traveller to east Africa | year=2003 | journal=Clin Infect Dis | volume=37 | pages=450–51 | doi=10.1086/375599 }}</ref> but there are other mechanisms of resistance that remain unknown.<ref>{{cite journal | author=Wichmann O, Muehlen M, Gruss H, ''et al.'' | title=Malarone treatment failure not associated with previously described mutations in the cytochrome b gene | year=2004 | journal=Malaria J | volume=3 | pages=14 | doi=10.1186/1475-2875-3-14 }}</ref>
==References==
{{reflist|2}}
==External links==
* [http://www.dartmouth.edu/~blt/Publications/JBC279,2817.pdf#search='Atovaquone' Molecular Basis for Atovaquone Resistance in Pneumocystis jirovecii]
* [http://www.lymenet.de/literatur/atovaquone.htm Atovaquone (Meprone)]
* [http://www.bnf.org British National Formulary]
{{Agents against amoebiasis and other protozoal diseases}}
[[Category:Antimalarial agents]]
[[Category:Organochlorides]]
[[Category:Quinones]]
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