Atovaquone: Difference between revisions
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==Overview== | |||
'''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''' (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> | ||
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[[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]]. | [[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]]. | ||
==Category== | |||
==US Brand Names== | |||
==FDA Package Insert== | |||
''' [[XXXXX description|Description]]''' | |||
'''| [[XXXXX clinical pharmacology|Clinical Pharmacology]]''' | |||
'''| [[XXXXX microbiology|Microbiology]]''' | |||
'''| [[XXXXX indications and usage|Indications and Usage]]''' | |||
'''| [[XXXXX contraindications|Contraindications]]''' | |||
'''| [[XXXXX warnings and precautions|Warnings and Precautions]]''' | |||
'''| [[XXXXX adverse reactions|Adverse Reactions]]''' | |||
'''| [[XXXXX drug interactions|Drug Interactions]]''' | |||
'''| [[XXXXX overdosage|Overdosage]]''' | |||
'''| [[XXXXX clinical studies|Clinical Studies]]''' | |||
'''| [[XXXXX dosage and administration|Dosage and Administration]]''' | |||
'''| [[XXXXX how supplied|How Supplied]]''' | |||
'''| [[XXXXX labels and packages|Labels and Packages]]''' | |||
==Mechanism of Action== | |||
==Malaria== | ==Malaria== | ||
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===Treatment=== | ===Treatment=== | ||
The adult treatment dose is four "standard" tablets once a day for three days. In children, the drug is prescribed by body weight: | 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; | *11 to 20 kg: 1 "standard" tablet once daily for 3 days; | ||
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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. | 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. | 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. | ||
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The duration of treatment is the same as for adults. | 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 [[Duodenal cytochrome B|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 }}</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 }}</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 }}</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 }}</ref> | Proguanil acts as a [[mitochondrion|mitochondrial]] sensitiser and synergizes with atovaquone; also, there is a high natural frequency of [[Duodenal cytochrome B|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 }}</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 }}</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 }}</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 }}</ref> | ||
==References== | ==References== | ||
{{ | {{Reflist|2}} | ||
[[Category:Antibiotics]] | |||
[[Category:Wikinfect]] | |||
Revision as of 00:57, 7 January 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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.[1] It is also manufactured in the US in the liquid form, or oral suspension, under the brand name Mepron.[2]
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.[3]
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.
Category
US Brand Names
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages
Mechanism of Action
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 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,[4][5][6] but there are other mechanisms of resistance that remain unknown.[7]
References
- ↑ (ATN) Atovaquone (Mepron; 566C80) Approved for Pneumocystis; Drug Development, Activism Success
- ↑ Mepron
- ↑ Malarone: New Malaria Medication With Fewer Side-effects
- ↑ 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&ndash, 29.
- ↑ 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.
- ↑ 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&ndash, 51.
- ↑ 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.