Fexinidazole

What is Fexinidazole?

• Fexinidazole Tablets is a nitroimidazole antimicrobial used to treat human African trypanosomiasis (sleeping sickness) caused by the parasite Trypanosoma brucei gambiense.

Fexinidazole

Fexinidazole Structural Formula V1

Trypanosoma brucei gambiense - trypomastigote

SymptomsAfricanTrypanosomiasis

What are the uses of this medicine?

• Fexinidazole Tablets are used 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.

Limitations of Use:

• Due to the decreased efficacy observed in patients with severe second stage HAT (cerebrospinal fluid white blood cell count (CSF-WBC) >100 cells/µL) due to T. brucei gambiense disease, Fexinidazole Tablets should only be used in these patients if there are no other available treatment options.

How does this medicine work?

• Fexinidazole is an antiprotozoal drug.
• Studies with Trypanosoma brucei and other protozoans suggest that, like for other nitro-containing drugs, the nitroreductase (NTR) enzyme plays an important role in the bioactivation of fexinidazole resulting in generation of reactive amines and damage to DNA and proteins.
• The activity of fexinidazole and its metabolites (M1 and M2) is trypanocidal and appears to be concentration and time dependent.
• Fexinidazole and its two metabolites, M1 and M2, are active against the trypanosomes of Trypanosoma brucei gambiense.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• known hypersensitivity to Fexinidazole Tablets and/or any nitroimidazole-class drugs (e.g., metronidazole, tinidazole)
• hepatic impairment
• Cockayne syndrome

What drug interactions can this medicine cause?

• Avoid concomitant use of herbal medicines and supplements during treatment with Fexinidazole Tablets.
• Coadministration of Fexinidazole Tablets with drugs known to block potassium channels (e.g., antiarrhythmics, neuroleptics, fluoroquinolones, imidazole and triazole antifungals, pentamidine) prolong the QT interval (e.g., antimalarials, phenothiazines, tricyclic antidepressants, terfenadine and astemizole, IV erythromycin, and quinolone antibacterial drugs) and/or induce bradycardia (such as β-blockers) should be avoided.

Is this medicine FDA approved?

• Fexinidazole was approved for medical use in the United States in July 2021.

How should this medicine be used?

Recommended dosage:

• Recommended Dosage of Fexinidazole Tablets in Patients 6 years of age and older and weighing at least 20 kg as below:

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
Greater than or equal to 20 kg to less than 35 kg	Loading dose	1,200 mg	2	4 days

Administration:

• Administer Fexinidazole Tablets, orally, once daily for a total of 10 days (loading dose plus maintenance dose) with food each day at about the same time of the day.
• Do not break or crush Fexinidazole Tablets.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 600 mg

This medicine is available in fallowing brand namesː

• FEXINIDAZOLE tablet

What side effects can this medication cause?

The most common side effects of this medicine include:

• headache
• vomiting
• insomnia
• nausea
• asthenia
• tremor
• decreased appetite
• dizziness
• hypocalcemia
• dyspepsia
• back pain
• upper abdominal pain
• hyperkalemia

What special precautions should I follow?

• Decreased efficacy was observed in patients treated with Fexinidazole Tablets as compared to nifurtimox-eflornithine combination therapy (NECT)-treated patients. Patients with severe second stage HAT (CSF-WBC >100 cells/µL) due to T. brucei gambiense disease should only be treated with Fexinidazole Tablets if there are no other available treatment options.
• 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.
• Adult patients treated with Fexinidazole Tablets reported a higher percentage of Central Nervous System (CNS) and psychiatric-related adverse reactions than those treated with nifurtimox eflornithine combination therapy (NECT). 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.
• Neutropenia (absolute neutrophil count less than 1,000 cells/mm3) has been reported in patients receiving Fexinidazole Tablets. Avoid concomitant use of drugs which may cause neutropenia and monitor leukocyte count periodically. Monitor patients with neutropenia for symptoms or signs of infection.
• Elevations in liver transaminases occurred in less than two percent of patients receiving Fexinidazole Tablets for the treatment of HAT. Evaluate liver-related laboratory tests at the start and during treatment.
• 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.
• Psychotic reactions have been reported in patients concurrently taking disulfiram and nitroimidazole-class drugs. Avoid use in patients who have taken disulfiram within the last two weeks.
• Advise the patient that Fexinidazole Tablets must be taken with food each day at about the same time of the day (e.g., during or immediately after the main meal of the day), to make sure it is adequately absorbed.
• Counsel the patient that they should not drive or use machines if they feel tired or dizzy. Dizziness, fatigue, asthenia, and somnolence have been reported following treatment with Fexinidazole Tablets.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• increased transaminases
• vomiting
• panic attack
• increased potassium
• decreased calcium

Management of overdosage:

• There is no specific antidote for Fexinidazole Tablets.
• Treatment should be supportive with appropriate monitoring.

Can this medicine be used in pregnancy?

• There are risks to the mother and fetus associated with untreated HAT due to T. brucei gambiense during pregnancy.
• 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.

Can this medicine be used in children?

• The safety and effectiveness of Fexinidazole Tablets for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitic) HAT due to Trypanosoma brucei gambiense have been established in pediatric patients aged 6 years and older and weighing at least 20 kg.
• The safety and efficacy of Fexinidazole Tablets have not been established in pediatric patients younger than 6 years old and/or less than 20 kg in body weight.

What are the active and inactive ingredients in this medicine?

Active Ingredient:

• FEXINIDAZOLE

Inactive Ingredients:

• CROSCARMELLOSE SODIUM
• LACTOSE MONOHYDRATE
• MAGNESIUM STEARATE
• MICROCRYSTALLINE CELLULOSE
• POVIDONE, UNSPECIFIED
• SODIUM LAURYL SULFATE

Who manufactures and distributes this medicine?

Manufactured by:

• sanofi-aventis U.S. LLC
• Bridgewater, NJ
• A SANOFI COMPANY

What should I know about storage and disposal of this medication?

• Store below 30°C (86°F).
• Store in the original package in order to protect from light and moisture.

• Dailymed label info on Fexinidazole
• FDA Fexinidazole

Fexinidazole Resources
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