Fexinidazole

Fexinidazole is an antiprotozoal drug [see Microbiology (12.4) ] .

• Fexinidazole Tablets are indicated for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in patients 6 years of age and older and weighing at least 20 kg. Fexinidazole Tablets is a nitroimidazole antimicrobial, indicated for the treatment of both first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in patients 6 years of age and older and weighing at least 20 kg.

• Fexinidazole Tablets are contraindicated in: Patients with known hypersensitivity to Fexinidazole Tablets and/or any nitroimidazole-class drugs (e.g., metronidazole, tinidazole). Patients with severe hepatic impairment [see Warnings and Precautions (5.5) , Adverse Reactions (6.1) , and Use in Specific Populations (8.7) ] .contraindicated

Administer Fexinidazole Tablets once daily with food each day at about the same time of the day. Do not break or crush tablets. ( 2.1 , 2.2 ) Recommended Dosage of Fexinidazole Tablets in Patients 6 years of age and older and weighing at least 20 kg ( 2.2 ) Body Weight Type of Dose Daily Dose Number of Tablets Duration of Treatment Greater than or equal to 35 kg Loading dose 1,800 mg 3 4 days Maintenance dose 1,200 mg 2 6 days Greater than or equal to 20 kg to less than 35 kg Loading dose 1,200 mg 2 4 days Maintenance dose 600 mg 1 6 days 2.1 Important Administration Instructions Patients should be closely followed by their healthcare provider during treatment with Fexinidazole Tablets. Fexinidazole Tablets must be administered with food [see Dosage and Administration (2.2) ] . Avoid consumption of alcoholic beverages during treatment with Fexinidazole Tablets and for at least 48 hours after completing therapy [see Warnings and Precautions (5.6) ] . If a first event of vomiting occurs after receiving Fexinidazole Tablets, do not re-dose . Administer the next dose the following day using the recommended treatment schedule [see Adverse Reactions (6.1) ] . If a scheduled dose is missed (not taken on the assigned day), normal dosing should resume the following day until the full course (10 days) of treatment has been completed . The clinical consequences of multiple missed doses of Fexinidazole Tablets are not known .

Decreased Efficacy in Severe Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. ( 1 , 5.1 ) QT Interval Prolongation: Prolongation of the QT interval due to Fexinidazole Tablets occurs in a concentration-dependent manner. Avoid use in patients with known prolongation, proarrhythmic conditions, and concomitant use with drugs that prolong the QT interval, those that block cardiac potassium channels, and/or those that induce bradycardia, or are inducers of hepatic CYP450. ( 5.2 , 7.1 , 7.2 , 12.2 ) Neuropsychiatric Adverse Reactions: Adverse reactions such as agitation, anxiety, abnormal behavior, depression, suicidal ideation, nightmares, hallucination, and personality change have been observed during therapy. Inform patients and their caregivers of the risk. Consider alternative therapy or increased monitoring of the patient, including hospitalization in patients with psychiatric disorders, or if these adverse reactions occur. ( 5.3 ) Neutropenia: Avoid concomitant use of drugs which may cause neutropenia and monitor leukocyte count periodically. Monitor patients with neutropenia for symptoms or signs of infection. ( 5.4 , 6.1 ) Potential for Hepatotoxicity: Evaluate liver-related laboratory tests at the start and during treatment. ( 4 , 5.5 ) Risk of Disulfiram-like Reactions Due to Concomitant Use with Alcohol: Nitroimidazole-class drugs may cause a disulfiram-like reaction in patients who concurrently consume alcohol. Advise patients to avoid consumption of alcohol during treatment with and for at least 48 hours after completing therapy.

The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling: Decreased Efficacy in Severe Human African Trypanosomiasis Caused by Trypanosoma brucei gambiense [see Warnings and Precautions (5.1) ] QT Interval Prolongation [see Warnings and Precautions (5.2) ] Neuropsychiatric Adverse Reactions [see Warnings and Precautions (5.3) ] Neutropenia [see Warnings and Precautions (5.4) ] Potential for Hepatotoxicity [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence >10%) are headache, vomiting, insomnia, nausea, asthenia, tremor, decreased appetite, dizziness, hypocalcemia, dyspepsia, back pain, upper abdominal pain, and hyperkalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Fexinidazole Tablets were evaluated for the treatment of HAT due to T. brucei gambiense in three clinical trials, of which one was comparative and two were noncomparative. Trial 1 compared the safety of Fexinidazole Tablets to nifurtimox-eflornithine combination therapy (NECT) in second stage, meningoencephalitic HAT (N=394).

Avoid use in patients with severe renal impairment. ( 8.6 ) 8.1 Pregnancy Risk Summary There are risks to the mother and fetus associated with untreated HAT due to T. brucei gambiense during pregnancy (see Clinical Considerations ) . Available data from clinical trials with fexinidazole use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects or miscarriage. There were no effects on prenatal development in embryo-fetal studies where pregnant rats were administered oral fexinidazole during organogenesis at a dose similar to the clinical dose based on AUC comparisons. Effects of fexinidazole on embryo-fetal development were observed in the rat and in the rabbit at doses harmful to the dams only. Exposure of fexinidazole and its metabolites at those maternal toxic doses in rats and rabbits were 2 times and less than 0.02 times the clinical exposure, respectively. In the prenatal and postnatal development study, administration of oral fexinidazole to pregnant rats during organogenesis and through lactation resulted in lower body weights in first generation offspring from dams treated at approximately 1.03 times the clinical exposure based on AUC comparisons. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

The pharmacokinetics (PK) of fexinidazole and its two pharmacologically active M1 (sulfoxide) and M2 (sulfone) metabolites following administration of the recommended adult dosage regimen of Fexinidazole Tablets in 12 healthy adult male subjects under fed conditions are presented in Table 5.

Randomized, controlled clinical studies were conducted in normal adult male subjects who were administered single or multiple oral doses of fexinidazole of up to 3,600 mg daily for 14 days (not an approved dose). The subjects experienced adverse reactions of increased transaminases, vomiting and panic attack [see Adverse Reactions (6.1) ] . Reported symptoms of overdosage in a pediatric HAT patient following ingestion of a higher than recommended dosing regimen in Trial 3 included vomiting over the first 5 days of treatment and increased potassium and decreased calcium levels from Day 11 to Week 9. There is no specific antidote for Fexinidazole Tablets. Treatment should be supportive with appropriate monitoring.

• Jul 16, 2021NDANDA214429Sanofi

1. 1Seizure550%
2. 2Pyrexia330%
3. 3Asphyxia220%
4. 4Completed Suicide220%
5. 5Headache220%
6. 6Treatment Failure220%
7. 7Abdominal Pain Upper110%
8. 8Acute Pulmonary Oedema110%
9. 9African Trypanosomiasis Relapse110%
10. 10Agitation110%
11. 11Anaemia110%
12. 12Asthenia110%
13. 13Balanoposthitis110%
14. 14Cerebrovascular Accident110%
15. 15Chills110%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Fexinidazole as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Pharmacokinetic and Tolerability Study of Fexinidazole in a Single Oral Dose in Adult Participants With Mild and Moderate Hepatic Impairment
  Completed · Phase 1 · Interventional · 21 enrolled · Sanofi
  NCT05607173updated 2025-09-19
• Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense
  Completed · Phase 2 · Phase 3 · Interventional · 45 enrolled · Drugs for Neglected Diseases
  NCT03974178updated 2025-01-30
• Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage
  Completed · Phase 3 · Interventional · 174 enrolled · Drugs for Neglected Diseases
  NCT03025789updated 2025-01-08
• Screen and Treat Implementation for HAT Control
  Withdrawn · Observational · 0 enrolled · Institute of Tropical Medicine, Belgium
  NCT05645822updated 2024-02-02
• Oral Fexinidazole Dosing Regimens for the Treatment of Adults With Chronic Indeterminate Chagas Disease
  Completed · Phase 2 · Interventional · 45 enrolled · Drugs for Neglected Diseases
  NCT03587766updated 2020-09-23
• Efficacy and Safety of Fexinidazole in Children at Least 6 Years Old and Weighing Over 20 kg With Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open Study, plug-in to the Pivotal Study
  Completed · Phase 2 · Phase 3 · Interventional · 125 enrolled · Drugs for Neglected Diseases
  NCT02184689updated 2020-06-24
• Efficacy and Safety of Fexinidazole in Patients With Stage 1 or Early Stage 2 Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open-label Cohort Study, plug-in to the Pivotal Study
  Completed · Phase 2 · Phase 3 · Interventional · 230 enrolled · Drugs for Neglected Diseases
  NCT02169557updated 2020-06-24
• Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
  Completed · Phase 2 · Phase 3 · Interventional · 394 enrolled · Drugs for Neglected Diseases
  NCT01685827updated 2018-02-20
• Human African Trypanosomiasis: First in Man Clinical Trial of a New Medicinal Product, the Fexinidazole
  Completed · Phase 1 · Interventional · 108 enrolled · Drugs for Neglected Diseases
  NCT00982904updated 2017-04-06
• Multiple Dose Study to Evaluate Security, Tolerance and Pharmacokinetic of Fexinidazole (Drug Candidate for Human African Trypanosomiasis) Administered With a Loading Dose and With Food
  Terminated · Phase 1 · Interventional · 30 enrolled · Drugs for Neglected Diseases
  NCT01483170updated 2017-03-31

Frequently asked questions

How does Fexinidazole work?

Fexinidazole is an antiprotozoal drug [see Microbiology (12.4) ] .

What is Fexinidazole used for?

According to FDA labeling, Fexinidazole carries indications including: Fexinidazole Tablets are indicated for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in patients 6 years of age and older and weighing at least 20 kg. Fexinidazole Tablets is a nitroimidazole antimicrobial, indicated for the treatment of both first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in patients 6 years of age and older and weighing at least 20 kg.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Fexinidazole?

Fexinidazole is classified as Nitroimidazole derivatives, Nitroimidazole Antimicrobial, Cytochrome P450 1A2 Inducers, Cytochrome P450 1A2 Inhibitors, Cytochrome P450 2B6 Inducers, Cytochrome P450 2B6 Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A4 Inhibitors, Cytochrome P450 3A5 Inhibitors, Multidrug and Toxin Extrusion Transporter 1 Inhibitors, Multidrug and Toxin Extrusion Transporter 2 K Inhibitors, Organic Anion Transporter 1 Inhibitors, Organic Anion Transporter 3 Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, Organic Cation Transporter 2 Inhibitors.

What are the contraindications for Fexinidazole?

Fexinidazole labeling lists contraindications including: Fexinidazole Tablets are contraindicated in: Patients with known hypersensitivity to Fexinidazole Tablets and/or any nitroimidazole-class drugs (e.g., metronidazole, tinidazole). Patients with severe hepatic impairment [see Warnings and Precautions (5.5) , Adverse Reactions (6.1) , and Use in Specific Populations (8.7) ] .. Always consult the full prescribing information and a clinician.