Fexinidazole - Fexinidazole tablet
(Fexinidazole)Fexinidazole - Fexinidazole tablet Prescribing Information
Contraindications (Fexinidazole Tablets are contraindicated in:
| 9/2024 |
Fexinidazole Tablets are indicated for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to
Administer Fexinidazole Tablets once daily with food each day at about the same time of the day. Do
- 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.
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
The recommended dosage of Fexinidazole Tablets for patients 6 years of age and older is according to body weight as described in Table 1 below.
| Body weight | Type of Dose | RecommendedAdminister Fexinidazole Tablets once daily with food each day at about the same time of the dayDaily Dose | Number of 600 mg Fexinidazole Tablets Daily | 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 |
| Body weight | Type of Dose | RecommendedAdminister Fexinidazole Tablets once daily with food each day at about the same time of the dayDaily Dose | Number of 600 mg Fexinidazole Tablets Daily | 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 |
Tablets: 600 mg of fexinidazole per tablet as pale-yellow, round, biconvex tablets debossed with "4512" on one side.
- Avoid use in patients with severe renal impairment. ()
8.6 Renal ImpairmentNo dosage adjustment is needed for patients with mild to moderate renal impairment with estimated glomerular filtration rates (eGFR) from 30 mL/min/1.73 m2to less than or equal to 89 mL/min/1.73 m2
[see Clinical Pharmacology (12.3)]. The pharmacokinetics of fexinidazole in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) is unknown. Avoid the use of Fexinidazole Tablets in patients with severe renal impairment.
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.,
5.5 Potential for HepatotoxicityElevations in liver transaminases occurred in less than two percent of patients receiving Fexinidazole Tablets for the treatment of HAT
[see Adverse reactions (6.1)and Overdosage (10)]. Evaluate liver-related laboratory tests at the start[see Contraindications (4)]and during treatment with Fexinidazole Tablets. Monitor patients who develop abnormal liver-related laboratory tests during treatment with Fexinidazole Tablets., and6.1 Clinical Trials ExperienceBecause 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 gambiensein 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). Trial 2 enrolled patients with stage 1 hemolymphatic and early stage 2 HAT (N=230), and Trial 3 assessed the safety of fexinidazole in pediatric patients aged 6 years or older with any stage HAT (N=125).The three trials were primarily conducted in the Democratic Republic of Congo (DRC) and a total of 749 patients received at least one dose of study medication. The patients ranged from 6 to 73 years of age, and 11 were more than 65 years old. Trials 1 and 3 enrolled more males than females (61% and 54% were males, respectively), while the gender distribution was equally balanced in Trial 2. The mean BMI ranged from 16.1 to 19.3 kg/m2across trials which was consistent with the nutritional status of the study population. Patients with AST/ALT >2 times the upper limit of normal or total bilirubin >1.5 the upper limit of normal were excluded from the trials.
Trial 1 included 264 patients in the fexinidazole treatment arm and 130 patients in the NECT treatment arm. The patients were followed for up to 24 months from the completion of treatment.
Common Adverse ReactionsThe most common adverse reactions occurring in >10% of HAT patients (15 years of age and older) receiving Fexinidazole Tablets in Trial 1 were headache, vomiting, insomnia, nausea, asthenia, tremor, decreased appetite, dizziness, hypocalcemia, dyspepsia, back pain, upper abdominal pain, and hyperkalemia.
Selected adverse reactions occurring in ≥2% of HAT patients 15 years of age and older receiving Fexinidazole Tablets in Trial 1 are provided in Table 2.
Table 2: Selected Adverse Reactions Occurring in ≥2% of HAT Patients 15 Years of Age and Older Receiving Fexinidazole Tablets in Trial 1 Adverse Reaction Fexinidazole Tablets
N=264
N (%)NECT
N=130
N (%)Blood and lymphatic system disordersNeutropeniaDefined as an absolute neutrophil count of less than 1,000 cells/mm3occurring at any time following the first dose of study drug to the end of the study. 15 (5.7%) 4 (3.1%) Cardiac disordersPalpitations 13 (4.9%) 5 (3.8%) Eye disordersPhotophobia 6 (2.3%) 0 Gastrointestinal disordersVomiting 75 (28.4%) 37 (28.4%) Nausea 68 (25.8%) 20 (15.4%) Dyspepsia 34 (12.9%) 10 (7.7%) Abdominal pain upper 27 (10.2%) 6 (4.6%) Salivary hypersecretion 16 (6.1%) 3 (2.3%) Constipation 13 (4.9%) 2 (1.5%) Abdominal distension 8 (3.0%) 0 Gastritis 8 (3.0%) 2 (1.5%) General disorders and administration site conditionsAsthenia 60 (22.7%) 19 (14.6%) Feeling hot 25 (9.5%) 3 (2.3%) Chest pain 23 (8.7%) 5 (3.8%) Gait disturbance 12 (4.5%) 2 (1.5%) Metabolism and nutrition disordersDecreased appetite 56 (21.2%) 24 (18.5%) Hypocalcemia 36 (13.6%) 3 (2.3%) Hypoalbuminemia 23 (8.7%) 4 (3.1%) Musculoskeletal and connective tissue disordersBack pain 30 (11.4%) 12 (9.2%) Neck pain 23 (8.7%) 7 (5.4%) Muscle Spasms 7 (2.7%) 1 (0.8%) Nervous system disordersHeadache 92 (34.8%) 32 (24.6%) Tremor 58 (22.0%) 15 (11.5%) Dizziness 50 (18.9%) 18 (13.8%) Extrapyramidal disorder 9 (3.4%) 2 (1.5%) Paresthesia 6 (2.3%) 0 Psychiatric disordersInsomnia 74 (28.0%) 15 (11.5%) Agitation 10 (3.8%) 1 (0.8%) Anxiety 10 (3.8%) 0 Abnormal behavior 7 (2.7%) 1 (0.8%) Respiratory, thoracic and mediastinal disordersCough 16 (6.0%) 6 (4.6%) Dyspnea 6 (2.3%) 1 (0.8%) Skin and subcutaneous tissue disordersPruritus 10 (3.8%) 4 (3.1%) Hyperhidrosis 7 (2.7%) 2 (1.5%) Vascular disordersHot flush 13 (4.9%) 4 (3.1%) Hypertension 12 (4.5%) 1 (0.8%) Other Adverse Reactions with Fexinidazole Tablets Occurring in Trial 1The following adverse reactions were reported in less than 2% of patients aged 15 years and older with HAT, treated with Fexinidazole Tablets in Trial 1:
Psychiatric Disorders:hallucinations, psychotic disorder, depression, personality change, suicidal ideationLaboratory Investigations:elevations of liver transaminases[see Warnings and Precautions (5.5)]and Overdosage (10)]The safety profile of Fexinidazole Tablets in Trials 2 and 3, including in pediatric subjects aged 6–15 years old, was similar to that of Trial 1
[see Use in Specific Populations (8.4)].Specific Adverse ReactionsVomiting
In the clinical trials, the incidence of vomiting within 30 minutes of administration of Fexinidazole Tablets was higher in pediatric patients (20%) than in adult patients (6.1%). There was a trend of increased incidence of vomiting during the loading phase. Generally, vomiting did not lead to treatment discontinuation.
]8.7 Hepatic ImpairmentNo dosage adjustment of Fexinidazole Tablets is recommended for patients with mild hepatic impairment (Child-Pugh Class A). Moderate hepatic impairment (Child-Pugh Class B) increases fexinidazole and its active metabolite M1 exposures, which may increase the risk of adverse reactions
[see Clinical Pharmacology (12.3)].Use of Fexinidazole Tablets is contraindicated in patients with severe hepatic impairment[see Contraindications (4)and Warnings and Precautions (5.5)]. - Patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole, another nitroimidazole drug, structurally related to fexinidazole, in patients with Cockayne syndrome[see.]
6.2 Postmarketing ExperienceThe following adverse reaction has been identified and reported during post-approval use of other nitroimidazole agents. Because the reports of this reaction are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.
Metronidazole, Another Nitroimidazole Product, Structurally Related to Fexinidazole: Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, another nitroimidazole agent structurally related to fexinidazole, have been reported in patients with Cockayne syndrome (latency from drug start to signs of liver failure as short as 2 days)
[see Contraindications (4)].