General Information

Fexinidazole is a nitroimidazole antimicrobial.

Fexinidazole is specifically 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 is supplied as tablets for oral administration. Fexinidazole Tablets must be administered with food. Avoid consumption of alcoholic beverages during treatment with Fexinidazole Tablets and for at least 48 hours after completing therapy. 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. If a scheduled dose is missed, 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.

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. The recommended dosage of Fexinidazole Tablets for patients 6 years of age and older is according to body weight as described below:

Mechanism of Action

Fexinidazole is an antiprotozoal drug. Studies with Trypanosoma brucei and other protozoans suggest that, like for other nitrocontaining 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. However, the precise mechanism by which fexinidazole and the two metabolites exhibit activity against T. brucei is not known.

Side Effects

Adverse effects associated with the use of Fexinidazole may include, but are not limited to, the following:

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

Clinical Trials

The efficacy and safety of Fexinidazole Tablets were evaluated in a randomized, comparative open-label trial conducted in adult patients with late second-stage HAT due to T. brucei gambiense. Patients (n=394) were randomized in a 2:1 ratio to a 10-day treatment regimen of either Fexinidazole Tablets (n=264) or nifurtimox-eflornithine combination therapy (NECT) (n=130). The mean age was 35 years (range 15 to 71) and 61% were male. The fexinidazole tablet group received 1,800 mg of Fexinidazole Tablets orally once daily on Days 1 through 4, followed by 1,200 mg orally once daily on Days 5 through 10, with all dosing in the fed state. The NECT control arm received nifurtimox tablets 15 mg/kg/day in three divided doses for 10 days as well as eflornithine injectable solution 400 mg/kg/day in two divided doses for 7 days. Patients were followed up at 3, 6, 12, 18, and 24 months after the end of treatment visit. The outcome at 18 months was considered a success if patients were classified as a cure or probable cure as defined below: 

• Cure: Patient is alive with no evidence of trypanosomes in any body fluid and CSF WBC ≤20 cells/µL.
• Probable cure for patients who refused a lumbar puncture (or who had a hemorrhagic CSF sample) at 18 months: No parasites in the blood or lymph and a satisfactory clinical condition without clinical signs or symptoms (or clinical status is unlikely to be due to HAT), CSF WBC <50 cells/µL at 6 and/or 12 months and not increasing at 12 months, as long as there was no indication of a relapse up to 24 months and no definitive failure (presence of trypanosomes) had been observed before in any body fluid.

Success at 18 months was reached by 91.2% of patients in the Fexinidazole arm and 97.6% in the NECT arm. 

Additional supportive evidence for efficacy in early stage HAT due to T. brucei gambiense, and in pediatric patients was obtained from two single-arm trials: a single-arm trial in adults, and a single-arm trial in pediatric patients aged 6 to 15 years old and weighing at least 20 kg. In Trial 2, the mean age of patients was 34 years and 82% of patients had evidence of first-stage HAT (evidence of trypanosomes in the blood or lymph, no trypanosomes in the CSF, and CSF WBC ≤5 cells /µL). In Trial 3, the mean age of patients was 11 years and 55% of patients had evidence of first-stage HAT. Fexinidazole Tablets 1,200 mg, was given in fed condition once a day on Days 1 through 4, followed by 600 mg on Days 5 through 10 to patients weighing <35 kg, and all other patients received the adult dosing regimen. Treatment success proportions in all patients with first- or late-stage HAT were 98.7% at 12 months in Trial 2 and 97.6% at 12 months in Trial 3. The results at 18 months were consistent with the results at 12 months.