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Combination of
AtovaquoneAntimalarial medication
ProguanilAntimalarial medication
Trade namesMalarone, Malanil, others
Clinical data
Main usesTreat and prevent malaria[1][2]
Side effectsAbdominal pain, vomiting, diarrhea, cough, itchiness[2]
  • US: C (Risk not ruled out)
Routes of
By mouth
Defined daily dosenot established[3]
External links
License data
Legal status
  • UK: POM (Prescription only)
  • In general: ℞ (Prescription only)

Atovaquone/proguanil, sold under the trade names Malarone among others, is a combination of two antimalarial medication atovaquone and proguanil.[2] It is used to treat and prevent malaria, including chloroquine-resistant malaria.[1][2] It is not recommended for severe or complicated malaria.[2] It is taken by mouth.[2]

Common side effects include abdominal pain, vomiting, diarrhea, cough, and itchiness.[2] Serious side effects may include anaphylaxis, Stevens–Johnson syndrome, hallucinations, and liver problems.[2][5] It is unclear if use during pregnancy or breastfeeding is safe for the baby.[6] It is not recommended to prevent malaria in those with poor kidney function.[5] Atovaquone works by interfering with the function of mitochondria in malaria while proguanil by blocking dihydrofolate reductase.[2]

Atovaquone/proguanil was approved for medical use in the United States in 2000.[2] It has been available as a generic medication since 2011.[7] In the United Kingdom it costs £2.10 per dose as of 2019.[5] The wholesale cost in the United States is $US 2.82 per dose as of 2019.[8]

Medical use

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. Also, stomach irritation may occur if one lies down within a half hour after taking this medicine.


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.[9] Specific mutations (Y268S, Y268C) have been shown to confer resistance in vivo,[10][11][12] but the other mechanisms of resistance remain unknown.[13]


The defined daily dose is not established.[3]

Side effects

Side effects are generally mild.[14] Some people experience coughing, diarrhea, dizziness, headache, loss of appetite, mouth sores, nausea, stomach pain, or weakness, the majority have none or few of these.[14]

Mechanism of action

Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasitic electron transport chain, collapsing the mitochondrial membrane potential.[15] 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.[16]

Proguanil, via its metabolite cycloguanil, functions as a dihydrofolate reductase inhibitor, halting parasitic deoxythymidylate synthesis.[17]


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.


Glaxo Wellcome patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013.[18] The U.S. Food and Drug Administration (FDA) approved a generic formulation from Glenmark Generics in 2011.[19] 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.[20]


  1. 1.0 1.1 Nakato, Halima; Vivancos, Roberto; Hunter, Paul R. (2007-11-01). "A systematic review and meta-analysis of the effectiveness and safety of atovaquone–proguanil (Malarone) for chemoprophylaxis against malaria". Journal of Antimicrobial Chemotherapy. 60 (5): 929–936. doi:10.1093/jac/dkm337. ISSN 0305-7453. PMID 17848375. Archived from the original on 2021-08-29. Retrieved 2016-05-03.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Atovaquone and Proguanil Hydrochloride Monograph for Professionals". American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 12 September 2019.
  3. 3.0 3.1 "WHOCC - ATC/DDD Index". Archived from the original on 1 July 2021. Retrieved 10 September 2020.
  4. "Glaxo Smith Kline monograph on MALARONE". Archived from the original on 2016-03-24. Retrieved 2012-08-03.
  5. 5.0 5.1 5.2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 604. ISBN 9780857113382.
  6. "Atovaquone / proguanil Use During Pregnancy". Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  7. "Generic Malarone Availability". Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  8. "NADAC as of 2019-09-11 |". Centers for Medicare and Medicaid Services. Archived from the original on 2019-12-30. Retrieved 12 September 2019.
  9. Srivastava, Indresh K.; Vaidya, Akhil B. (1999-06-01). "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. ISSN 0066-4804. PMC 89274. PMID 10348748.
  10. Färnet A, Lindberg J, Gil P, et al. (2003). "Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguoanil hydrochloride: case reports". Br Med J. 326 (7390): 628–29. doi:10.1136/bmj.326.7390.628. PMC 151974. PMID 12649236.
  11. 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 Journal. 1: 1. doi:10.1186/1475-2875-1-1. PMC 111499. PMID 12057021.
  12. 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 (3): 450–51. doi:10.1086/375599. PMID 12884171.
  13. Wichmann O, Muehlen M, Gruss H, et al. (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.
  14. 14.0 14.1 "Malarone Side Effects: Common, Severe, Long Term". Archived from the original on 16 August 2019. Retrieved 12 September 2019.
  15. Fry, Mitchell; Pudney, Mary (1992-04-01). "Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3- hydroxy-1,4-naphthoquinone (566C80)". Biochemical Pharmacology. 43 (7): 1545–1553. doi:10.1016/0006-2952(92)90213-3. PMID 1314606.
  16. Srivastava, Indresh K.; Rottenberg, Hagai; Vaidya, Akhil B. (1997-02-14). "Atovaquone, a Broad Spectrum Antiparasitic Drug, Collapses Mitochondrial Membrane Potential in a Malarial Parasite". Journal of Biological Chemistry. 272 (7): 3961–3966. doi:10.1074/jbc.272.7.3961. ISSN 0021-9258. PMID 9020100.
  17. "Archive copy" (PDF). Archived (PDF) from the original on 2011-09-04. Retrieved 2011-09-28.{{cite web}}: CS1 maint: archived copy as title (link)
  18. "Generic Malarone Availability". Archived from the original on 2019-08-16. Retrieved 2018-01-23.
  19. "Drug Details". Archived from the original on 2021-08-27. Retrieved 2013-05-01.
  20. "Atovaquone Proguanil (Malarone) Patent Revoked & Glenmark Launches First UK Generic". Archived from the original on 2013-04-16. Retrieved 2013-05-01.

External links