Atovaquone

Atovaquone is a quinone antimicrobial drug [see Clinical Pharmacology ( 12.4 )] .

• Atovaquone oral suspension is a quinone antimicrobial drug indicated for: Prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents aged 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). ( 1.1 ) Treatment of mild-to-moderate PCP in adults and adolescents aged 13 years and older who cannot tolerate TMP-SMX.ICD-10: J18.9

• Atovaquone oral suspension is contraindicated in patients who develop or have a history of hypersensitivity reactions (e.g., angioedema, bronchospasm, throat tightness, urticaria) to atovaquone or any of the components of atovaquone oral suspension. Known serious allergic/hypersensitivity reaction (e.g., angioedema, bronchospasm, throat tightness, urticaria) to atovaquone or any of the components of atovaquone oral suspension.contraindicated

Prevention of PCP: 1,500 mg (10 mL) once daily with food ( 2.1 ) Treatment of PCP: 750 mg (5 mL) twice daily with food for 21 days ( 2.2 ) Supplied in Bottles: Shake bottle gently before use. ( 2.3 ) 2.1 Dosage for the Prevention of P. jirovecii Pneumonia The recommended oral dosage is 1,500 mg (10 mL) once daily administered with food. 2.2 Dosage for the Treatment of Mild-to-Moderate P. jirovecii Pneumonia The recommended oral dosage is 750 mg (5 mL) twice daily (total daily dose = 1,500 mg) administered with food for 21 days. 2.3 Important Administration Instructions Administer atovaquone oral suspension with food to avoid lower plasma atovaquone concentrations that may limit response to therapy [see Warnings and Precautions ( 5.1), Clinical Pharmacology ( 12.3 )] . Atovaquone Oral Suspension Bottle Shake bottle gently before administering the recommended dosage.

Failure to administer atovaquone oral suspension with food may result in lower plasma atovaquone concentrations and may limit response to therapy. Patients with gastrointestinal disorders may have limited absorption resulting in suboptimal atovaquone concentrations. ( 5.1 ) Hepatotoxicity: Elevated liver chemistry tests and cases of hepatitis and fatal liver failure have been reported. ( 5.2 ) 5.1 Risk of Limited Oral Absorption Absorption of orally administered atovaquone oral suspension is limited but can be significantly increased when the drug is taken with food. Failure to administer atovaquone oral suspension with food may result in lower plasma atovaquone concentrations and may limit response to therapy. Consider therapy with other agents in patients who have difficulty taking atovaquone oral suspension with food or in patients who have gastrointestinal disorders that may limit absorption of oral medications [see Clinical Pharmacology ( 12.3 )]. 5.2 Hepatotoxicity Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure have been reported in patients treated with atovaquone [see Adverse Reactions ( 6.2 )]. If treating patients with severe hepatic impairment, closely monitor patients following administration of atovaquone oral suspension.

The following adverse reactions are discussed in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions ( 5.2 )] . PCP Prevention: The most frequent adverse reactions (≥25% that required discontinuation) were diarrhea, rash, headache, nausea, and fever. ( 6.1 ) PCP Treatment: The most frequent adverse reactions (≥14% that required discontinuation) were rash (including maculopapular), nausea, diarrhea, headache, vomiting, and fever. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Additionally, because many subjects who participated in clinical trials with atovaquone had complications of advanced human immunodeficiency virus (HIV) disease, it was often difficult to distinguish adverse reactions caused by atovaquone from those caused by underlying medical conditions. PCP Prevention Trials In 2 clinical trials, atovaquone oral suspension was compared with dapsone or aerosolized pentamidine in HIV-1-infected adolescent (13 to 18 years) and adult subjects at risk of PCP (CD4 count <200 cells/mm 3 or a prior episode of PCP) and unable to tolerate TMP-SMX.

8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Atovaquone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Atovaquone was not teratogenic and did not cause reproductive toxicity in rats at plasma concentrations up to 2 to 3 times the estimated human exposure (dose of 1,000 mg/kg/day in rats). Atovaquone caused maternal toxicity in rabbits at plasma concentrations that were approximately one-half the estimated human exposure. Mean fetal body lengths and weights were decreased and there were higher numbers of early resorption and post-implantation loss per dam (dose of 1,200 mg/kg/day in rabbits). It is not clear whether these effects were caused by atovaquone directly or were secondary to maternal toxicity. Concentrations of atovaquone in rabbit fetuses averaged 30% of the concurrent maternal plasma concentrations. In a separate study in rats given a single 14 C-radiolabelled dose (1,000 mg/kg), concentrations of radiocarbon in rat fetuses were 18% (middle gestation) and 60% (late gestation) of concurrent maternal plasma concentrations. 8.3 Nursing Mothers It is not known whether atovaquone is excreted into human milk. Because many drugs are excreted into human milk, caution should be exercised when atovaquone is administered to a nursing woman.

Metabolism

Absorption Atovaquone is a highly lipophilic compound with low aqueous solubility. The bioavailability of atovaquone is highly dependent on formulation and diet.

In one patient who took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose. There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable.

• Feb 8, 1995NDANDA020500Glaxosmithkline Llc
• Jul 14, 2000NDANDA021078Glaxosmithkline
• Jan 12, 2011ANDAANDA091211Glenmark Pharms Ltd
• Mar 18, 2014ANDAANDA202960Amneal Pharms
• May 27, 2014ANDAANDA202362Mylan
• Apr 28, 2017ANDAANDA207833Chartwell Rx
• Oct 11, 2018ANDAANDA210692Hetero Labs Ltd Iii
• Nov 21, 2018ANDAANDA209685Glenmark Speclt

1. 1Off Label Use7898.0%
2. 2Pyrexia5825.9%
3. 3Diarrhoea5785.9%
4. 4Nausea5595.7%
5. 5Drug Ineffective5155.2%
6. 6Vomiting4064.1%
7. 7Fatigue4034.1%
8. 8Pneumonia3974.0%
9. 9Rash3463.5%
10. 10Dyspnoea3453.5%
11. 11Death3103.2%
12. 12Headache2983.0%
13. 13Thrombocytopenia2903.0%
14. 14Condition Aggravated2812.9%
15. 15Acute Kidney Injury2712.8%

Recent PubMed references pinned to Atovaquone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Ruthenium Complexes of Atovaquone Acting on Multiple Stages of the Plasmodium Life Cycle.
  Journal of medicinal chemistry · 2026 · Fabbri C, Marcon PHS, Santiago AS, et al.
  PMID 41964606DOI 10.1021/acs.jmedchem.5c02978
• Downregulation of TDP43 by atovaquone inhibits oxidative phosphorylation and enhances sensitivity of triple-negative breast cancer to EGFR-TKIs.
  Free radical biology & medicine · 2026 · Lin L, Ke H, Chen M, et al.
  PMID 41862009DOI 10.1016/j.freeradbiomed.2026.03.047
• Atovaquone/proguanil use and zoster vaccination are associated with reduced Alzheimer's disease risk in two cohorts: implications for a latent Toxoplasma gondii mechanism.
  Brain, behavior, and immunity · 2026 · Israel A, Weizman A, Israel S, et al.
  PMID 41619985DOI 10.1016/j.bbi.2026.106473
• Artesunate-pyronaridine-atovaquone-proguanil and artesunate-fosmidomycin-clindamycin compared with standard artesunate-pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana.
  The Lancet. Microbe · 2026 · Agobé JCD, Maïga-Ascofaré O, Adegnika AA, et al.
  PMID 41616788DOI 10.1016/j.lanmic.2025.101245
• Congenital babesiosis in China: first molecularly confirmed case of vertical transmission of Babesia microti.
  Emerging microbes & infections · 2026 · Liu J, Li D, Wang S, et al.
  PMID 41559018DOI 10.1080/22221751.2025.2608389
• Atovaquone-induced oxidative stress activates the pentose phosphate pathway and Immunogenic cell death in ovarian cancer.
  Scientific reports · 2025 · Betancourt Ponce M, Boonpattrawong N, Fagan AJ, et al.
  PMID 41286323DOI 10.1038/s41598-025-25704-y
• 4-nitrobenzoate inhibits 4-hydroxybenzoate polyprenyltransferase in malaria parasites and enhances atovaquone efficacy.
  FEBS letters · 2026 · Verdaguer IB, Santos MF, Filho MM, et al.
  PMID 41088842DOI 10.1002/1873-3468.70186
• Complete attenuation of Plasmodium falciparum sporozoites by atovaquone-proguanil.
  EMBO molecular medicine · 2025 · Borrmann S, Sulyok Z, Müller K, et al.
  PMID 41023197DOI 10.1038/s44321-025-00301-8

The 10 most recently updated of 58 ClinicalTrials.gov registrations naming Atovaquone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• First-in-Human PfSPZ-LARC2 Vaccination/CHMI
  Active not recruiting · Phase 1 · Interventional · 22 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06735209updated 2026-06-12
• Efficacy, Safety, and PK of M5717 in Combination With Pyronaridine as Chemoprevention in Adults and Adolescents With Asymptomatic Plasmodium Falciparum Infection (CAPTURE-2)
  Completed · Phase 2 · Interventional · 192 enrolled · Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  NCT05974267updated 2026-02-06
• Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC
  Completed · Phase 1 · Interventional · 21 enrolled · University of Oxford
  NCT04648033updated 2026-01-29
• Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML)
  Completed · Early phase 1 · Interventional · 26 enrolled · Baylor College of Medicine
  NCT03568994updated 2026-01-27
• Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives)
  Not yet recruiting · Phase 4 · Interventional · 416 enrolled · McGill University Health Centre/Research Institute of the McGill University Health Centre
  NCT07357103updated 2026-01-21
• Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer
  Recruiting · Phase 2 · Interventional · 28 enrolled · Emory University
  NCT05998135updated 2025-09-11
• Atovaquone Combined With Radiation in Children With Malignant Brain Tumors
  Recruiting · Phase 1 · Interventional · 18 enrolled · Emory University
  NCT06624371updated 2025-07-22
• A Study to Evaluate Antimalarial Activity and Safety of MK-7602 in Healthy Adults (MK-7602-003)
  Completed · Phase 1 · Interventional · 16 enrolled · Merck Sharp & Dohme LLC
  NCT06294912updated 2025-01-13
• Safety and Efficacy of NF135 CPS Immunization
  Terminated · Interventional · 43 enrolled · Radboud University Medical Center
  NCT03813108updated 2023-05-26
• Atoguanil BA Study
  Completed · Phase 1 · Interventional · 16 enrolled · Medicines for Malaria Venture
  NCT04866602updated 2022-05-05

Frequently asked questions

How does Atovaquone work?

Atovaquone is a quinone antimicrobial drug [see Clinical Pharmacology ( 12.4 )] .

What is Atovaquone used for?

According to FDA labeling, Atovaquone carries indications including: Atovaquone oral suspension is a quinone antimicrobial drug indicated for: Prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents aged 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). ( 1.1 ) Treatment of mild-to-moderate PCP in adults and adolescents aged 13 years and older who cannot tolerate TMP-SMX.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Atovaquone?

Atovaquone is classified as Other agents against amoebiasis and other protozoal diseases, Antimalarial, Antiprotozoal, Nucleic Acid Synthesis Inhibitors, Decreased Metabolic Rate.

What are the brand names for Atovaquone?

Atovaquone is marketed under brand names including Malarone, Mepron.

What are the contraindications for Atovaquone?

Atovaquone labeling lists contraindications including: Atovaquone oral suspension is contraindicated in patients who develop or have a history of hypersensitivity reactions (e.g., angioedema, bronchospasm, throat tightness, urticaria) to atovaquone or any of the components of atovaquone oral suspension. Known serious allergic/hypersensitivity reaction (e.g., angioedema, bronchospasm, throat tightness, urticaria) to atovaquone or any of the components of atovaquone oral suspension.. Always consult the full prescribing information and a clinician.