African trypanosomiasis (sleeping sickness), first-stage (hemolymphatic) or second-stage (with CNS involvement) disease, caused by Trypanosoma brucei gambiense:
Note: Patients with severe second-stage infection (cerebrospinal fluid WBC >100 cells/mm3) should not be treated with fexinidazole if other treatment options (eg, nifurtimox-eflornithine combination therapy) are available.
Children ≥6 years and Adolescents, weighing ≥20 kg:
20 to <35 kg: Oral: Initial: 1,200 mg once daily for 4 days, followed by a maintenance dose of 600 mg once daily for 6 days to complete a 10-day course.
≥35 kg: Oral: Initial: 1,800 mg once daily for 4 days, followed by a maintenance dose of 1,200 mg once daily for 6 days to complete a 10-day course.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents, weighing ≥20 kg:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: Avoid use (has not been studied).
Children ≥6 years and Adolescents, weighing ≥20 kg: Mild to severe impairment: Use is contraindicated.
(For additional information see "Fexinidazole (United States: Not commercially available; refer to 'Product Availability' field): Drug information")
Human African trypanosomiasis: Oral:
20 to <35 kg: 1.2 g once daily for 4 days; followed by 600 mg once daily for 6 days.
≥35 kg: 1.8 g once daily for 4 days; followed by 1.2 g once daily for 6 days.
Missed dose: If a dose is missed (ie, not taken on the assigned day), normal dosing should resume the following day until the full course (10 days) is complete (Ref). If a dose is missed during days 1 to 4 and >1 day has passed, restart treatment course. If a dose is missed during days 5 to 10, ensure that ≥3 doses (out of the 6 doses of the maintenance phase) are correctly taken; while not ideal, a minimum of 7 doses taken correctly (complete loading dose phase [days 1 to 4] plus ≥3 doses during the maintenance phase [days 5 to 10]) can be considered acceptable. If a second dose is missed, consider alternative treatment (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: Avoid use (has not been studied).
Use is contraindicated.
Neuropsychiatric effects, including agitation, anxiety, abnormal behavior, depression, suicidal ideation, nightmares, hallucinations, personality changes, headache, insomnia, and tremor have been observed during fexinidazole therapy.
Risk factors:
• History of psychiatric disorders
• Psychotic reactions: Concomitant use with disulfiram or disulfiram use within the past 2 weeks
Fexinidazole prolonged QT interval on ECG in a concentration-dependent manner (average increase of 19 msec in the QTcF interval).
Risk factors:
Drug-induced QTc prolongation/torsades de pointes (TdP) (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)
• Genetic defects of cardiac ion channels (Ref)
• History of drug-induced TdP (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Loop diuretic use (Ref)
• Sepsis (Ref)
• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults unless otherwise indicated.
>10%:
Endocrine & metabolic: Hypocalcemia (14%)
Gastrointestinal: Decreased appetite (21%), dyspepsia (13%), nausea (26%), vomiting (28%; pediatric patients: 20%, adult patients: 6%)
Nervous system: Dizziness (19%), headache (35%) (table 1) , insomnia (28%) (table 2)
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
35% |
25% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
28% |
12% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
Neuromuscular & skeletal: Asthenia (23%), back pain (11%), tremor (22%) (table 3)
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
22% |
12% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
1% to 10%:
Cardiovascular: Chest pain (9%), hypertension (5%), palpitations (5%)
Dermatologic: Hyperhidrosis (3%), pruritus (4%)
Endocrine & metabolic: Hot flash (5%), hypoalbuminemia (9%)
Gastrointestinal: Abdominal distention (3%), constipation (5%), gastritis (3%), sialorrhea (6%), upper abdominal pain (10%)
Hematologic & oncologic: Neutropenia (6%)
Hepatic: Increased serum transaminases (<2%)
Nervous system: Abnormal behavior (3%) (table 4) , abnormal gait (5%), agitation (4%) (table 5) , anxiety (4%) (table 6) , depression (<2%), extrapyramidal reaction (3%), feeling hot (10%), hallucination (<2%), paresthesia (2%), personality changes (<2%), psychotic symptoms (<2%), suicidal ideation (<2%)
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
3% |
0.8% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
4% |
0.8% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
Drug (Fexinidazole) |
Comparator (Nifurtimox-Eflornithine Combination Therapy) |
Population |
Indication |
Number of Patients (Fexinidazole) |
Number of Patients (Nifurtimox-Eflornithine Combination Therapy) |
---|---|---|---|---|---|
4% |
0% |
Adolescents and adults |
Second stage, meningoencephalitic human African trypanosomiasis |
264 |
130 |
Neuromuscular & skeletal: Muscle spasm (3%), neck pain (9%)
Ophthalmic: Photophobia (2%)
Respiratory: Cough (6%), dyspnea (2%)
Frequency not defined:
Cardiovascular: Prolonged QT interval on ECG
Nervous system: Nightmares
Hypersensitivity to fexinidazole, other nitroimidazole derivatives (eg, metronidazole, tinidazole), or any component of the formulation; hepatic impairment.
Concerns related to adverse effects:
• Neutropenia: Neutropenia has been reported in patients receiving fexinidazole, particularly in patients with a baseline ANC <5,000/mm3. Avoid concomitant use of medications that may cause neutropenia and monitor leukocyte count periodically.
Disease-related concerns:
• Hepatic impairment: Use is contraindicated.
• Renal impairment: Avoid use in patients with severe impairment (eGFR <30 mL/minute/1.73 m2).
Product is not commercially available in the United States; contact Sanofi regarding supply and distribution at https://www.sanofi.us or 1-800-981-2491.
Product is not commercially available in the United States; contact Sanofi regarding supply and distribution at https://www.sanofi.us or 1-800-981-2491.
Oral: Swallow tablets whole; do not break or crush. Administer during or immediately after the main meal of the day (within 30 minutes of the meal). A meal should consist of ≥250 mL of solid food; liquid food is not enough for adequate absorption (Ref). If a first event of vomiting occurs <2 hours after the administration of fexinidazole, do not administer an additional dose; continue with the next scheduled dose the following day (consider use of an antiemetic), and extend treatment 1 day longer. If vomiting occurs >2 hours after fexinidazole administration, the dose is assumed to be sufficiently absorbed. If a second event of vomiting occurs after administration of any other dose, consider an alternative regimen (Ref).
Missed doses: If a dose is missed (ie, not taken on the assigned day), normal dosing should resume the following day until the full course (10 days) is complete (Ref). If a dose is missed during days 1 to 4 and >1 day has passed, restart treatment course. If a dose is missed during days 5 to 10, ensure that ≥3 doses (out of the 6 doses of the maintenance phase) are correctly taken; while not ideal, a minimum of 7 doses taken correctly (complete loading dose phase [days 1 to 4] plus ≥3 doses during the maintenance phase [days 5 to 10]) can be considered acceptable. If a second dose is missed, consider alternative treatment (Ref).
Oral: Administer during or immediately after the main meal of the day, within 30 minutes of that meal. A meal should consist of at least 250 mL of solid food; liquid food is not enough for adequate absorption (Ref). Swallow tablet whole (do not break or crush). If a first event of vomiting occurs <2 hours after the administration of fexinidazole, do not administer an additional dose; continue with the next scheduled dose the following day (consider use of an antiemetic), and extend treatment 1 day longer. If vomiting occurs >2 hours after fexinidazole administration, the dose is assumed to be sufficiently absorbed. If a second event of vomiting occurs after administration of any other dose, consider an alternative regimen (Ref).
Store below 30°C (86°F). Protect from light and moisture.
Treatment of first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense (FDA approved in ages ≥6 years and weighing ≥20 kg and adults). Note: Due to the decreased efficacy observed in patients with severe second-stage T. brucei gambiense disease (cerebrospinal fluid WBC >100 cells/mm3), fexinidazole should only be used in these patients if there are no other available treatment options.
Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (moderate), CYP2C19 (moderate)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abrocitinib: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Abrocitinib. Risk C: Monitor therapy
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Fexinidazole. A disulfiram-like reaction may occur. Risk X: Avoid combination
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy
Belzutifan: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Belzutifan. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Brivaracetam. Risk C: Monitor therapy
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Carisoprodol. Risk C: Monitor therapy
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Citalopram: Fexinidazole may enhance the QTc-prolonging effect of Citalopram. Fexinidazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with fexinidazole, which is a moderate CYP2C19 inhibitor. Monitor for citalopram toxicity (eg, serotonin syndrome), QTc prolongation, and arrhythmias (including torsades de pointes). Risk D: Consider therapy modification
CloBAZam: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy
CloZAPine: Fexinidazole may enhance the QTc-prolonging effect of CloZAPine. Fexinidazole may increase the serum concentration of CloZAPine. Management: Monitor for increased clozapine toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
CYP2B6 Substrates (High risk with Inducers): Fexinidazole may decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Management: Avoid concomitant use of fexinidazole and CYP2B6 substrates when possible. If combined, monitor for reduced efficacy of the CYP2B6 substrate. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Avoid use of fexinidazole and moderate CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Avoid use of fexinidazole and strong CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
CYP3A4 Substrates (High risk with Inhibitors): Fexinidazole may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Dabrafenib: Fexinidazole may enhance the QTc-prolonging effect of Dabrafenib. Dabrafenib may decrease the serum concentration of Fexinidazole. Risk X: Avoid combination
Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Dexlansoprazole. Risk C: Monitor therapy
Disulfiram: Fexinidazole may enhance the adverse/toxic effect of Disulfiram. Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy
Encorafenib: Fexinidazole may enhance the QTc-prolonging effect of Encorafenib. Encorafenib may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Escitalopram: Fexinidazole may enhance the QTc-prolonging effect of Escitalopram. Fexinidazole may increase the serum concentration of Escitalopram. Management: Monitor for increased escitalopram toxicities (including increased QTc prolongation and serotonin syndrome) if combined with fexinidazole. Consider limiting the escitalopram dose to 10 mg daily when these agents are combined. Risk C: Monitor therapy
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Fluorouracil Products: May enhance the myelosuppressive effect of Fexinidazole. Fexinidazole may enhance the QTc-prolonging effect of Fluorouracil Products. Risk X: Avoid combination
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Grapefruit Juice: May decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Advise patients taking fexinidazole to avoid consumption of grapefruit juice. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Lansoprazole. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lonafarnib: May enhance the QTc-prolonging effect of Fexinidazole. Fexinidazole may increase the serum concentration of Lonafarnib. Lonafarnib may increase the serum concentration of Fexinidazole. Risk X: Avoid combination
MATE1/2-K Substrates (Clinically Relevant with Inhibitors): Fexinidazole may increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider therapy modification
Mavacamten: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Risk X: Avoid combination
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy
Moclobemide: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Moclobemide. Risk C: Monitor therapy
Myelosuppressive Agents: May enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
OAT1/3 Substrates (Clinically Relevant): Fexinidazole may increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
OCT2 Substrates (Clinically Relevant with Inhibitors): Fexinidazole may increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with OCT2 substrates when possible. If combined, monitor for increased OCT2 substrate toxicities. Risk D: Consider therapy modification
OLANZapine: Fexinidazole may enhance the QTc-prolonging effect of OLANZapine. Fexinidazole may increase the serum concentration of OLANZapine. Management: Monitor for increased olanzapine toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Omeprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Omeprazole. Risk C: Monitor therapy
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Probucol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Proguanil: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Proguanil. Risk C: Monitor therapy
Propofol: May enhance the arrhythmogenic effect of Fexinidazole. Propofol may enhance the QTc-prolonging effect of Fexinidazole. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): Fexinidazole may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of Fexinidazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of Fexinidazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Fexinidazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): Fexinidazole may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): Fexinidazole may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Fexinidazole. Risk X: Avoid combination
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider therapy modification
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider therapy modification
Following administration with food, the AUC of fexinidazole and its active metabolites was approximately 4- to 5-fold higher compared to the fasted state. Management: Administer during or immediately after the main meal of the day.
Food: Take during or immediately after the main meal of the day.
Ethanol: Avoid use of ethanol during treatment and for at least 48 hours after therapy discontinuation.
Adverse events were observed in animal reproduction studies with doses that were also maternally toxic.
Treatment of human African trypanosomiasis during pregnancy is recommended. Fexinidazole can be given after the first trimester to reduce the risk of fetal transmission of the disease, and to prevent maternal death in patients with moderate or severe disease (WHO 2019).
LFTs and electrolytes (baseline and during treatment); CBC with differential; monitor for neuropsychiatric adverse effects including agitation, anxiety, abnormal behavior, depression, nightmares, hallucination, mood and personality changes, and suicidal ideation.
Fexinidazole is a nitroimidazole derivative that is thought to be trypanocidal via bioactivation by parasite nitroreductase enzymes to generate reactive amines and damage DNA and proteins.
Absorption: Rapid; administration with food increases AUC 4- to 5-fold relative to administration in fasted state.
Distribution: Vd: 3,222 ± 1,199 L.
Protein binding: Fexinidazole: 98%; fexinidazole sulfoxide: 41%; fexinidazole sulfone: 57%.
Metabolism: Hepatic via CYP-450; fexinidazole is extensively metabolized to active metabolites fexinidazole sulfoxide and fexinidazole sulfone.
Half-life elimination: Fexinidazole: 15 ± 6 hours; fexinidazole sulfoxide: 16 ± 6 hours; fexinidazole sulfone: 23 ± 4 hours.
Excretion: Urine (<3.2%; as metabolites).
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