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{{Short description|Chemical compound}}
{{Use dmy dates|date=April 2023}}
{{Drugbox {{Drugbox
| Verifiedfields = changed
| verifiedrevid = 458781507
⚫ | type = combo


<!--Combo data--> <!--Combo data-->
⚫ | type = combo
| component1 = Atovaquone | component1 = Atovaquone
| class1 = ] | class1 = ]
Line 9: Line 13:


<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename = Malarone, Malanil, others
| Drugs.com = {{drugs.com|monograph|atovaquone-and-proguanil-hydrochloride}} | Drugs.com = {{drugs.com|monograph|atovaquone-and-proguanil-hydrochloride}}
| licence_EU = <!-- EMEA requires brand name --> | licence_EU = <!-- EMEA requires brand name -->
| DailyMedID = Atovaquone_and_proguanil
| licence_US = Malarone
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU = B2<!-- A / B1 / B2 / B3 / C / D / X -->
⚫ | routes_of_administration = ]
| pregnancy_US =
⚫ | ATC_prefix = P01
| pregnancy_category =
⚫ | ATC_suffix = BB51
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| ATC_supplemental =

| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Atovaquopro Lupin (Generic Health Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=28 September 2022 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/atovaquopro-lupin-generic-health-pty-ltd | access-date=29 April 2023 |archive-date=12 October 2022 |archive-url=https://web.archive.org/web/20221012060341/https://www.tga.gov.au/resources/prescription-medicines-registrations/atovaquopro-lupin-generic-health-pty-ltd |url-status=live }}</ref>
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = POM | legal_UK = POM
| legal_US = | legal_US = Rx-only
| legal_status = Rx | legal_status = Rx-only
| dependency_liability =
⚫ | routes_of_administration = ]


<!--Identifiers--> <!--Identifiers-->
| CAS_number = 156879-69-5
⚫ | ATC_prefix = P01
⚫ | ATC_suffix = BB51
| StdInChI = 1S/C22H19ClO3.C11H16ClN5.ClH/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26;1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9;/h1-4,9-13,15,26H,5-8H2;3-7H,1-2H3,(H5,13,14,15,16,17);1H/t13-,15-;;
| StdInChIKey = VLGMAGFZQDMEGN-BKRMEZGBSA-N
| PubChem = 11954242 | PubChem = 11954242
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21230364 | ChemSpiderID = 21230364
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = <!-- blanked - oldvalue: D02472 -->
| KEGG = D02472
<!--Chemical data-->
}} }}
<!-- Definition and medical uses -->
⚫ ]
'''Atovaquone/proguanil''', sold under the brand name '''Malarone''' among others, is a ] medication used to treat and prevent ], including ]-resistant malaria.<ref>{{cite journal | vauthors = Nakato H, Vivancos R, Hunter PR | title = A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria | journal = The Journal of Antimicrobial Chemotherapy | volume = 60 | issue = 5 | pages = 929–936 | date = November 2007 | pmid = 17848375 | doi = 10.1093/jac/dkm337 | doi-access = free }}</ref><ref name=AHSF2019>{{cite web |title=Atovaquone and Proguanil Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/atovaquone-and-proguanil-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=12 September 2019 |language=en |archive-date=20 December 2016 |archive-url=https://web.archive.org/web/20161220223925/https://www.drugs.com/monograph/atovaquone-and-proguanil-hydrochloride.html |url-status=live }}</ref> It contains ] and ].<ref name=AHSF2019/> It is not recommended for severe or complicated malaria.<ref name=AHSF2019/> It is taken by mouth.<ref name=AHSF2019/>


<!-- Side effects and mechanism -->
The ] combination ''']/]''' (], trade name '''Malarone''') is an ] used in both the treatment and prevention of ], commercially available from ] since 2000. Atovaquone alone is not indicated for treatment or prevention of malaria as ] (i.e. without proguanil).
Common side effects include abdominal pain, vomiting, diarrhea, cough, and itchiness.<ref name=AHSF2019/> Serious side effects may include ], ], ], and liver problems.<ref name=AHSF2019/><ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=604|edition=76}}</ref> Side effects are generally mild.<ref name=Drug2019Side/> It is unclear if use during pregnancy or breastfeeding is safe for the baby.<ref>{{cite web |title=Atovaquone / proguanil Use During Pregnancy |url=https://www.drugs.com/pregnancy/atovaquone-proguanil.html |website=Drugs.com |access-date=12 September 2019 |language=en |archive-date=16 August 2019 |archive-url=https://web.archive.org/web/20190816072546/https://www.drugs.com/pregnancy/atovaquone-proguanil.html |url-status=live }}</ref> It is not recommended to prevent malaria in those with poor kidney function.<ref name=BNF76/> Atovaquone works by interfering with the function of ] in malaria while proguanil blocks ].<ref name=AHSF2019/>


<!-- History and culture -->
⚫ 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.
Atovaquone/proguanil was approved for medical use in the United States in 2000.<ref name=AHSF2019/> It has been available as a ] since 2011.<ref>{{cite web |title=Generic Malarone Availability |url=https://www.drugs.com/availability/generic-malarone.html |website=Drugs.com |access-date=12 September 2019 |language=en |archive-date=16 August 2019 |archive-url=https://web.archive.org/web/20190816072535/https://www.drugs.com/availability/generic-malarone.html |url-status=live }}</ref>


==Medical use== ==Medical uses==
⚫ ]
===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.


===Malaria treatment===
Malarone is not licensed for use in children weighing 10&nbsp;kg or less. The "pediatric" tablets are ''not'' used in malaria treatment.
Atovaquone/proguanil is not normally used to treat severe malaria, when an injectable drug such as ] is used instead.{{cn|date=December 2022}}


===Malaria prevention===
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 (] or ] in the UK; ] in the US) should be used instead.
Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil frequently causes if taken without food. {{cn|date=December 2022}}


===Prevention=== ===Resistance===
⚫ Proguanil acts as a ] sensitiser and synergizes with atovaquone. When atovaquone is used as a sole agent, a high natural frequency of ] mutants leads to a high failure rate. This is potentially due to the high lipophilicity and slow uptake of atovaquone, which results in a relatively prolonged period of parasite exposure at ineffective concentrations.<ref>{{cite journal | vauthors = Srivastava IK, Vaidya AB | title = A mechanism for the synergistic antimalarial action of atovaquone and proguanil | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 6 | pages = 1334–1339 | date = June 1999 | pmid = 10348748 | pmc = 89274 | doi = 10.1128/AAC.43.6.1334 }}</ref> Specific mutations (''Y268S'', ''Y268C'') have been shown to confer resistance ''in vivo'',<ref>{{cite journal | vauthors = Färnert A, Lindberg J, Gil P, Swedberg G, Berqvist Y, Thapar MM, Lindegårdh N, Berezcky S, Björkman A | display-authors = 6 | title = Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports | journal = BMJ | volume = 326 | issue = 7390 | pages = 628–629 | date = March 2003 | pmid = 12649236 | pmc = 151974 | doi = 10.1136/bmj.326.7390.628 }}</ref><ref>{{cite journal | vauthors = Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G | title = Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria | journal = Malaria Journal | volume = 1 | pages = 1 | date = February 2002 | pmid = 12057021 | pmc = 111499 | doi = 10.1186/1475-2875-1-1 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schwartz E, Bujanover S, Kain KC | title = Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa | journal = Clinical Infectious Diseases | volume = 37 | issue = 3 | pages = 450–451 | date = August 2003 | pmid = 12884171 | doi = 10.1086/375599 | doi-access = free }}</ref> but the other mechanisms of resistance remain unknown.<ref>{{cite journal | vauthors = Wichmann O, Muehlen M, Gruss H, Mockenhaupt FP, Suttorp N, Jelinek T | title = Malarone treatment failure not associated with previously described mutations in the cytochrome b gene | journal = Malaria Journal | volume = 3 | pages = 14 | date = June 2004 | pmid = 15186499 | pmc = 425592 | doi = 10.1186/1475-2875-3-14 | doi-access = free }}</ref>
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 ] sensitiser and synergizes with atovaquone; also, there is a high natural frequency of ] 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 | issue=7390 | pmc=151974 }}</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 | pmid=12884171 | issue=3 }}</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 | pmid=15186499 | pmc=425592 }}</ref>


==Adverse effects== ==Adverse effects==
Side effects are generally mild.<ref name=Drug2019Side/> While some people experience side effects, such as coughing, diarrhea, dizziness, headache, loss of appetite, mouth sores, nausea, stomach pain, vomiting, or weakness, the majority have none or few of these.<ref name=Drug2019Side>{{cite web |title=Malarone Side Effects: Common, Severe, Long Term |url=https://www.drugs.com/sfx/malarone-side-effects.html |website=Drugs.com |access-date=12 September 2019 |language=en |archive-date=16 August 2019 |archive-url=https://web.archive.org/web/20190816072534/https://www.drugs.com/sfx/malarone-side-effects.html |url-status=live }}</ref>
Some people have difficulty sleeping (nightmares, incoherent dreams) while taking Malarone. Headaches and stomach irritation have also been reported, though this can be helped by taking the drug with food or a milky drink. Muscle fatigue and hard stools have also been reported.


==Mechanism of action== ==Mechanism of action==
Atovaquone selectively inhibits the malarial cytochrome ''bc''<sub>1</sub> complex in the parasitic ], collapsing the mitochondrial membrane potential.<ref>{{cite journal | vauthors = Fry M, Pudney M | title = Site of action of the antimalarial hydroxynaphthoquinone, 2--3-hydroxy-1,4-naphthoquinone (566C80) | journal = Biochemical Pharmacology | volume = 43 | issue = 7 | pages = 1545–1553 | date = April 1992 | pmid = 1314606 | doi = 10.1016/0006-2952(92)90213-3 }}</ref> The malarial electron transport chain does not contribute significantly to ATP synthesis; thus, it is believed that parasite death is due to the indirect inhibition of dihydroorotate dehydrogenase, which requires transport chain function and is essential to pyrimidine biosynthesis.<ref>{{cite journal | vauthors = Srivastava IK, Rottenberg H, Vaidya AB | title = Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 3961–3966 | date = February 1997 | pmid = 9020100 | doi = 10.1074/jbc.272.7.3961 | doi-access = free }}</ref>
Atovaquone selectively inhibits the parasitic ].


Proguanil, via its metabolite ], functions as a ], halting parasitic ] synthesis.<ref>http://us.gsk.com/products/assets/us_malarone.pdf</ref> Proguanil, via its metabolite ], functions as a ], halting parasitic ] synthesis.<ref>{{Cite web|url=http://us.gsk.com/products/assets/us_malarone.pdf|title=Our prescription medicines &#124; GSK US|access-date=28 September 2011|archive-date=4 September 2011|archive-url=https://web.archive.org/web/20110904232305/http://us.gsk.com/products/assets/us_malarone.pdf|url-status=dead}}</ref>


==References== ===Chemistry===
⚫ A standard tablet of Malarone contains 100&nbsp;mg of proguanil hydrochloride and 250&nbsp;mg of atovaquone. A pediatric tablet contains 25&nbsp;mg of proguanil hydrochloride and 62.5&nbsp;mg of atovaquone.{{cn|date=December 2022}}

==History==
] patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013.<ref name="generic">{{Cite web |url=https://www.drugs.com/availability/generic-malarone.html |title=Generic Malarone Availability |access-date=23 January 2018 |archive-date=16 August 2019 |archive-url=https://web.archive.org/web/20190816072535/https://www.drugs.com/availability/generic-malarone.html |url-status=live }}</ref> The U.S. ] (FDA) approved a generic formulation from ] in 2011.<ref name="fda_generic">{{Cite web |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=091211&DrugName=ATOVAQUONE%20AND%20PROGUANIL%20HYDROCHLORIDE&ActiveIngred=ATOVAQUONE%3B%20PROGUANIL%20HYDROCHLORIDE&SponsorApplicant=GLENMARK%20GENERICS&ProductMktStatus=1&goto=Search.DrugDetails |title=Drug Details |access-date=1 May 2013 |archive-date=27 August 2021 |archive-url=https://web.archive.org/web/20210827232613/https://www.accessdata.fda.gov/scripts/cder/daf/ |url-status=live }}</ref> In February 2013, the ] High Court revoked Glaxo's patent on grounds of obviousness, which clears the way for firms to sell generic versions there.<ref name="uk">{{Cite web |url=http://www.prnewswire.co.uk/news-releases/atovaquone-proguanil-malarone-patent-revoked--glenmark-launches-first-uk-generic-190203571.html |title=Atovaquone Proguanil (Malarone) Patent Revoked & Glenmark Launches First UK Generic |access-date=1 May 2013 |archive-date=16 April 2013 |archive-url=https://web.archive.org/web/20130416001054/http://www.prnewswire.co.uk/news-releases/atovaquone-proguanil-malarone-patent-revoked--glenmark-launches-first-uk-generic-190203571.html |url-status=live }}</ref>

== References ==
{{Reflist}} {{Reflist}}


{{Antimalarials|state=collapsed}}
⚫ ]
{{GlaxoSmithKline}}
{{Portal bar | Medicine}}

{{DEFAULTSORT:Atovaquone Proguanil}}
⚫ ]
] ]
] ]
]

]
]
]

Latest revision as of 20:52, 14 September 2024

Chemical compound

Pharmaceutical compound
Atovaquone/proguanil
Combination of
AtovaquoneAntimalarial medication
ProguanilAntimalarial medication
Clinical data
Trade namesMalarone, Malanil, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
KEGG
CompTox Dashboard (EPA)
  (what is this?)  (verify)

Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended for severe or complicated malaria. It is taken by mouth.

Common side effects include abdominal pain, vomiting, diarrhea, cough, and itchiness. Serious side effects may include anaphylaxis, Stevens–Johnson syndrome, hallucinations, and liver problems. Side effects are generally mild. It is unclear if use during pregnancy or breastfeeding is safe for the baby. It is not recommended to prevent malaria in those with poor kidney function. Atovaquone works by interfering with the function of mitochondria in malaria while proguanil blocks dihydrofolate reductase.

Atovaquone/proguanil was approved for medical use in the United States in 2000. It has been available as a generic medication since 2011.

Medical uses

Malarone tablets, as issued in the UK.

Malaria treatment

Atovaquone/proguanil is not normally used to treat severe malaria, when an injectable drug such as quinine is used instead.

Malaria prevention

Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil frequently causes if taken without food.

Resistance

Proguanil acts as a mitochondrial sensitiser and synergizes with atovaquone. When atovaquone is used as a sole agent, a high natural frequency of cytochrome b mutants leads to a high failure rate. This is potentially due to the high lipophilicity and slow uptake of atovaquone, which results in a relatively prolonged period of parasite exposure at ineffective concentrations. Specific mutations (Y268S, Y268C) have been shown to confer resistance in vivo, but the other mechanisms of resistance remain unknown.

Adverse effects

Side effects are generally mild. While some people experience side effects, such as coughing, diarrhea, dizziness, headache, loss of appetite, mouth sores, nausea, stomach pain, vomiting, or weakness, the majority have none or few of these.

Mechanism of action

Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasitic electron transport chain, collapsing the mitochondrial membrane potential. The malarial electron transport chain does not contribute significantly to ATP synthesis; thus, it is believed that parasite death is due to the indirect inhibition of dihydroorotate dehydrogenase, which requires transport chain function and is essential to pyrimidine biosynthesis.

Proguanil, via its metabolite cycloguanil, functions as a dihydrofolate reductase inhibitor, halting parasitic deoxythymidylate synthesis.

Chemistry

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

History

Glaxo Wellcome patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013. The U.S. Food and Drug Administration (FDA) approved a generic formulation from Glenmark Generics in 2011. In February 2013, the United Kingdom High Court revoked Glaxo's patent on grounds of obviousness, which clears the way for firms to sell generic versions there.

References

  1. "Atovaquopro Lupin (Generic Health Pty Ltd)". Therapeutic Goods Administration (TGA). 28 September 2022. Archived from the original on 12 October 2022. Retrieved 29 April 2023.
  2. Nakato H, Vivancos R, Hunter PR (November 2007). "A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria". The Journal of Antimicrobial Chemotherapy. 60 (5): 929–936. doi:10.1093/jac/dkm337. PMID 17848375.
  3. ^ "Atovaquone and Proguanil Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 12 September 2019.
  4. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 604. ISBN 9780857113382.
  5. ^ "Malarone Side Effects: Common, Severe, Long Term". Drugs.com. Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  6. "Atovaquone / proguanil Use During Pregnancy". Drugs.com. Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  7. "Generic Malarone Availability". Drugs.com. Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  8. Srivastava IK, Vaidya AB (June 1999). "A mechanism for the synergistic antimalarial action of atovaquone and proguanil". Antimicrobial Agents and Chemotherapy. 43 (6): 1334–1339. doi:10.1128/AAC.43.6.1334. PMC 89274. PMID 10348748.
  9. Färnert A, Lindberg J, Gil P, Swedberg G, Berqvist Y, Thapar MM, et al. (March 2003). "Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports". BMJ. 326 (7390): 628–629. doi:10.1136/bmj.326.7390.628. PMC 151974. PMID 12649236.
  10. Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G (February 2002). "Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria". Malaria Journal. 1: 1. doi:10.1186/1475-2875-1-1. PMC 111499. PMID 12057021.
  11. Schwartz E, Bujanover S, Kain KC (August 2003). "Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa". Clinical Infectious Diseases. 37 (3): 450–451. doi:10.1086/375599. PMID 12884171.
  12. Wichmann O, Muehlen M, Gruss H, Mockenhaupt FP, Suttorp N, Jelinek T (June 2004). "Malarone treatment failure not associated with previously described mutations in the cytochrome b gene". Malaria Journal. 3: 14. doi:10.1186/1475-2875-3-14. PMC 425592. PMID 15186499.
  13. Fry M, Pudney M (April 1992). "Site of action of the antimalarial hydroxynaphthoquinone, 2--3-hydroxy-1,4-naphthoquinone (566C80)". Biochemical Pharmacology. 43 (7): 1545–1553. doi:10.1016/0006-2952(92)90213-3. PMID 1314606.
  14. Srivastava IK, Rottenberg H, Vaidya AB (February 1997). "Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite". The Journal of Biological Chemistry. 272 (7): 3961–3966. doi:10.1074/jbc.272.7.3961. PMID 9020100.
  15. "Our prescription medicines | GSK US" (PDF). Archived from the original (PDF) on 4 September 2011. Retrieved 28 September 2011.
  16. "Generic Malarone Availability". Archived from the original on 16 August 2019. Retrieved 23 January 2018.
  17. "Drug Details". Archived from the original on 27 August 2021. Retrieved 1 May 2013.
  18. "Atovaquone Proguanil (Malarone) Patent Revoked & Glenmark Launches First UK Generic". Archived from the original on 16 April 2013. Retrieved 1 May 2013.
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