Atovaquone 2869000 221290012 2008-06-23T21:44:59Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{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&nbsp;mg of proguanil hydrochloride and 250&nbsp;mg of atovaquone. A "pediatric" tablet of Malarone contains 25&nbsp;mg of proguanil hydrochloride and 62.5&nbsp;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&nbsp;kg: 1 "standard" tablet once daily for 3 days; *21 to 30&nbsp;kg: 2 "standard" tablets once daily for 3 days; *31 to 40&nbsp;kg: 3 "standard" tablets once daily for 3 days; *41&nbsp;kg and above: use adult dose. Malarone is not licensed for use in children weighing 10&nbsp;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&ndash;20&nbsp;kg: 1 "pediatric" tablet once daily; *21&ndash;30&nbsp;kg: 2 "pediatric" tablets once daily; *31&ndash;40&nbsp;kg: 3 "pediatric" tablets once daily; *41&nbsp;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&ndash;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&ndash;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]] [[de:Atovaquon]] [[fr:Atovaquone]] [[pl:Atowakwon]]