Proguanil

Atovaquone and proguanil hydrochloride tablets, a fixed-dose combination of atovaquone and proguanil hydrochloride, are an antimalarial agent [see Microbiology (12.4) ] .

• Atovaquone and proguanil hydrochloride tablets are an antimalarial indicated for: prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. ( 1.1 ) treatment of acute, uncomplicated P.ICD-10: B54

• Atovaquone and proguanil hydrochloride tablets are contraindicated in individuals with known hypersensitivity reactions (e.g., anaphylaxis, erythema multiforme or Stevens-Johnson syndrome, angioedema, vasculitis) to atovaquone or proguanil hydrochloride or any component of the formulation. Atovaquone and proguanil hydrochloride tablets are contraindicated for prophylaxis of P.contraindicated

The daily dose should be taken at the same time each day with food or a milky drink. In the event of vomiting within 1 hour after dosing, a repeat dose should be taken. Atovaquone and proguanil hydrochloride tablets may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets. Atovaquone and proguanil hydrochloride tablets should be taken with food or a milky drink. Prophylaxis ( 2.1 ) : Start prophylaxis 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return. Adults: One adult strength tablet per day. Pediatric Patients: Dosage based on body weight (see Table 1). Treatment ( 2.2 ) : Adults: Four adult strength tablets as a single daily dose for 3 days. Pediatric Patients: Dosage based on body weight (see Table 2). Renal Impairment ( 2.3 ) : Do not use for prophylaxis of malaria in patients with severe renal impairment. Use with caution for treatment of malaria in patients with severe renal impairment. 2.1 Prevention of Malaria Start prophylactic treatment with atovaquone and proguanil hydrochloride tablets 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return. Adults One atovaquone and proguanil hydrochloride tablet (adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day. Pediatric Patients The dosage for prevention of malaria in pediatric patients is based upon body weight (Table 1). Table 1.

Atovaquone absorption may be reduced in patients with diarrhea or vomiting. If used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required. ( 5.1 ) In mixed P. falciparum and Plasmodium vivax infection, P. vivax relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride tablets alone. ( 5.2 ) In the event of recrudescent P. falciparum infections after treatment or prophylaxis failure, patients should be treated with a different blood schizonticide. ( 5.2 ) Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use. ( 5.3 ) Atovaquone and proguanil hydrochloride tablets have not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria. Patients with severe malaria are not candidates for oral therapy. ( 5.4 ) 5.1 Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If atovaquone and proguanil hydrochloride tablets are used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered [see Dosage and Administration (2) ]. Vomiting occurred in up to 19% of pediatric patients given treatment doses of atovaquone and proguanil hydrochloride tablets.

Prophylaxis: Common adverse reactions (≥ 4%) in adults were diarrhea, dreams, oral ulcers, and headache; these events occurred in a similar or lower proportion of subjects receiving atovaquone and proguanil hydrochloride tablets than an active comparator. Common adverse reactions (≥ 5%) in pediatric patients included abdominal pain, headache, cough, and vomiting. ( 6.1 ) Treatment: Common adverse reactions (≥ 5%) in adolescents and adults were abdominal pain, nausea, vomiting, headache, diarrhea, asthenia, anorexia, and dizziness. Common adverse reactions (≥ 6%) in pediatric patients included vomiting, pruritus, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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. Because atovaquone and proguanil hydrochloride tablets contain atovaquone and proguanil hydrochloride, the type and severity of adverse reactions associated with each of the compounds may be expected. The lower prophylactic doses of atovaquone and proguanil hydrochloride tablets were better tolerated than the higher treatment doses.

Renal impairment: contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment. ( 8.6 ) 8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience with use of atovaquone and proguanil hydrochloride tablets in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. The proguanil component of atovaquone and proguanil hydrochloride tablets acts to inhibit parasitic dihydrofolate reductase; however, pregnant women and females of reproductive potential should continue folate supplementation to prevent neural tube defects [see Clinical Pharmacology (12.4) ] . Pregnant women with malaria are at increased risk for adverse pregnancy outcomes (see Clinical Considerations ) . Atovaquone administered by oral gavage to pregnant rats and rabbits during the period of organogenesis was not associated with fetal malformations at plasma exposures approximately 7 times and equal to, respectively, the estimated human exposure for the treatment of malaria based on AUC.

Metabolism

Absorption Atovaquone is a highly lipophilic compound with low aqueous solubility. The bioavailability of atovaquone shows considerable inter-individual variability.

There is no information on overdoses of atovaquone and proguanil hydrochloride tablets substantially higher than the doses recommended for treatment. There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable. Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose. Overdoses of proguanil hydrochloride as large as 1,500 mg have been followed by complete recovery, and doses as high as 700 mg twice daily have been taken for over 2 weeks without serious toxicity. Adverse experiences occasionally associated with proguanil hydrochloride doses of 100 to 200 mg/day, such as epigastric discomfort and vomiting, would be likely to occur with overdose. There are also reports of reversible hair loss and scaling of the skin on the palms and/or soles, reversible aphthous ulceration, and hematologic side effects.

• Jul 14, 2000NDANDA021078Glaxosmithkline
• Jan 12, 2011ANDAANDA091211Glenmark Pharms Ltd
• May 27, 2014ANDAANDA202362Mylan

1. 1Nausea1868.8%
2. 2Diarrhoea1708.0%
3. 3Pyrexia1497.1%
4. 4Vomiting1497.1%
5. 5Headache1306.2%
6. 6Malaria1235.8%
7. 7Drug Ineffective1205.7%
8. 8Dizziness1115.3%
9. 9Fatigue1075.1%
10. 10Malaise1024.8%
11. 11Rash823.9%
12. 12Hallucination763.6%
13. 13Insomnia703.3%
14. 14Abdominal Pain693.3%
15. 15Anxiety693.3%

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

• 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
• 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
• The impact of acacetin on proguanil metabolism: An in vitro and in vivo study.
  Biochemical pharmacology · 2026 · Fu H, Jiang S, Wang P, et al.
  PMID 41241020DOI 10.1016/j.bcp.2025.117539
• 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
• Atovaquone-proguanil and reduced digestive cancer risk: a Toxoplasma gondii connection.
  Gut microbes · 2025 · Israel A, Israel S, Weizman A, et al.
  PMID 40788706DOI 10.1080/19490976.2025.2545412
• Travellers' adherence to atovaquone/proguanil malaria chemoprophylaxis after return from endemic areas.
  Travel medicine and infectious disease · 2025 · Schnyder JL, Birkhoff DC, Jarings MC, et al.
  PMID 39892439DOI 10.1016/j.tmaid.2025.102812
• Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi-physiologic population pharmacokinetic approach.
  Clinical and translational science · 2024 · Khwarg J, Yang E, Park CS, et al.
  PMID 39668580DOI 10.1111/cts.70103
• Preparation, optimization, and evaluation of ligand-tethered atovaquone-proguanil-loaded nanoparticles for malaria treatment.
  Journal of biomaterials science. Polymer edition · 2025 · Patil A, Singh G, Dighe RD, et al.
  PMID 39522102DOI 10.1080/09205063.2024.2422704

The 10 most recently updated of 46 ClinicalTrials.gov registrations naming Proguanil 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
• 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
• Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE)
  Completed · Phase 4 · Interventional · 246 enrolled · Duke University
  NCT03178643updated 2024-04-23
• 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
• Study to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers
  Completed · Phase 1 · Interventional · 19 enrolled · Seoul National University Hospital
  NCT04568772updated 2021-09-27
• Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis.
  Completed · Phase 4 · Interventional · 103 enrolled · State University of New York - Upstate Medical University
  NCT02564471updated 2021-05-13
• Malarone Pharmacokinetics Under Simulated Physiologic Stressors of Deployment
  Withdrawn · Phase 4 · Interventional · 0 enrolled · Walter Reed Army Institute of Research (WRAIR)
  NCT03991208updated 2021-04-30
• The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia
  Unknown · Phase 4 · Interventional · 205 enrolled · Armed Forces Research Institute of Medical Sciences, Thailand
  NCT02297477updated 2021-03-02

Frequently asked questions

How does Proguanil work?

Atovaquone and proguanil hydrochloride tablets, a fixed-dose combination of atovaquone and proguanil hydrochloride, are an antimalarial agent [see Microbiology (12.4) ] .

What is Proguanil used for?

According to FDA labeling, Proguanil carries indications including: Atovaquone and proguanil hydrochloride tablets are an antimalarial indicated for: prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. ( 1.1 ) treatment of acute, uncomplicated P.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Proguanil?

Proguanil is classified as Biguanides, Antimalarial, Dihydrofolate Reductase Inhibitors, Decreased DNA Integrity.

What are the brand names for Proguanil?

Proguanil is marketed under brand names including Malarone.

What are the contraindications for Proguanil?

Proguanil labeling lists contraindications including: Atovaquone and proguanil hydrochloride tablets are contraindicated in individuals with known hypersensitivity reactions (e.g., anaphylaxis, erythema multiforme or Stevens-Johnson syndrome, angioedema, vasculitis) to atovaquone or proguanil hydrochloride or any component of the formulation. Atovaquone and proguanil hydrochloride tablets are contraindicated for prophylaxis of P.. Always consult the full prescribing information and a clinician.