Version July 2025
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).
Child-Turcotte-Pugh class A: No dosage adjustment necessary.
Child-Turcotte-Pugh class B: There are no dosage adjustments provided in the manufacturer's labeling; fexinidazole and its active metabolite exposure may be increased leading to an increased risk of adverse reactions.
Child-Turcotte-Pugh class C: Use is contraindicated.
Refer to adult dosing.
(For additional information see "Fexinidazole (United States: Not commercially available; refer to 'Product Availability' field): Pediatric drug information")
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.
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; severe hepatic impairment; Cockayne syndrome.
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.
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: 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).
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).
Human African trypanosomiasis: Treatment of first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in patients ≥6 years of age and weighing ≥20 kg.
Limitations of use: Due to the decreased efficacy observed in patients with severe second-stage HAT (cerebrospinal fluid white blood cell count >100 cells/mm3) due to T. brucei gambiense disease, 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); Induces CYP3A4 (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.
Abemaciclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abemaciclib. Risk X: Avoid
Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abiraterone Acetate. Risk C: Monitor
Abrocitinib: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Abrocitinib. Risk C: Monitor
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Agomelatine. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Fexinidazole. A disulfiram-like reaction may occur. Risk X: Avoid
Alosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider Therapy Modification
Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor
ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALPRAZolam. Risk C: Monitor
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
AmLODIPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of AmLODIPine. Risk C: Monitor
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase active metabolite exposure of Anagrelide. Risk C: Monitor
Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid
Apremilast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Apremilast. Risk C: Monitor
ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole. Risk C: Monitor
Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk C: Monitor
Atogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atorvastatin. Risk C: Monitor
Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid
Avacopan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avacopan. Risk X: Avoid
Avanafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification
Bedaquiline: Fexinidazole may increase QTc-prolonging effects of Bedaquiline. Fexinidazole may decrease serum concentration of Bedaquiline. Fexinidazole may increase active metabolite exposure of Bedaquiline. Risk X: Avoid
Belumosudil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Belumosudil. Risk C: Monitor
Belzutifan: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Belzutifan. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor
Bradycardia-Causing Agents: May increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brexpiprazole. Risk C: Monitor
Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Brivaracetam. Risk C: Monitor
Buprenorphine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inducers (Moderate) may decrease serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabis: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor
Capivasertib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capivasertib. Risk X: Avoid
Capmatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capmatinib. Risk X: Avoid
Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid
Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase serum concentration of Carisoprodol. Risk C: Monitor
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider Therapy Modification
Citalopram: Fexinidazole may increase QTc-prolonging effects of Citalopram. Fexinidazole may increase 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
Clarithromycin: May increase QTc-prolonging effects of Fexinidazole. Clarithromycin may decrease active metabolite exposure of Fexinidazole. Fexinidazole may decrease serum concentration of Clarithromycin. Fexinidazole may increase active metabolite exposure of Clarithromycin. Management: If coadministration is unavoidable, monitor for decreased efficacy of clarithromycin and fexinidazole and QTc interval prolongation and ventricular arrhythmias when these agents are combined. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor
CloBAZam: CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase serum concentration of CloBAZam. Risk C: Monitor
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ClomiPRAMINE. Risk C: Monitor
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Clopidogrel. Risk C: Monitor
CloZAPine: Fexinidazole may increase QTc-prolonging effects of CloZAPine. Fexinidazole may decrease serum concentration of CloZAPine. Fexinidazole may increase serum concentration of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Monitor for both increased and decreased clozapine serum concentrations and effects. Risk C: Monitor
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Codeine. Risk C: Monitor
Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP2B6 Substrates (High risk with Inducers): Fexinidazole may decrease 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 active metabolite exposure of Fexinidazole. Risk X: Avoid
CYP3A4 Inducers (Strong): May increase active metabolite exposure of Fexinidazole. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May decrease active metabolite exposure 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 active metabolite exposure 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
Dabrafenib: Fexinidazole may increase QTc-prolonging effects of Dabrafenib. Dabrafenib may decrease serum concentration of Fexinidazole. Risk X: Avoid
Daclatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification
Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Dapsone (Systemic). Risk C: Monitor
Daridorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daridorexant. Risk X: Avoid
Dasabuvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dasabuvir. Risk X: Avoid
Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Dexlansoprazole. Risk C: Monitor
DiazePAM: CYP2C19 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
DiazePAM: CYP3A4 Inducers (Moderate) may decrease serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dienogest: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dienogest. Risk C: Monitor
Disulfiram: Fexinidazole may increase adverse/toxic effects of Disulfiram. Risk X: Avoid
Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Doravirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Doravirine. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of DroNABinol. Risk C: Monitor
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of DULoxetine. Risk C: Monitor
Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dydrogesterone. Risk C: Monitor
Elacestrant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor
Eliglustat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Eliglustat. Risk C: Monitor
Encorafenib: Fexinidazole may increase QTc-prolonging effects of Encorafenib. Fexinidazole may decrease serum concentration of Encorafenib. Encorafenib may increase active metabolite exposure of Fexinidazole. Risk X: Avoid
Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: Fexinidazole may increase QTc-prolonging effects of Entrectinib. Fexinidazole may decrease serum concentration of Entrectinib. Risk X: Avoid
Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification
Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification
Escitalopram: Fexinidazole may increase QTc-prolonging effects of Escitalopram. Fexinidazole may increase 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
Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Exemestane: CYP3A4 Inducers (Moderate) may decrease serum concentration of Exemestane. Risk C: Monitor
Fedratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fedratinib. Risk X: Avoid
Felodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Felodipine. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Fezolinetant. Risk X: Avoid
Finerenone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Flibanserin. Risk X: Avoid
Fluorouracil Products: May increase myelosuppressive effects of Fexinidazole. Fexinidazole may increase QTc-prolonging effects of Fluorouracil Products. Risk X: Avoid
Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor
Fostamatinib: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fostamatinib. Risk C: Monitor
Fruquintinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Ganaxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification
Gefitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gefitinib. Risk C: Monitor
Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor
Gepirone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepirone. Risk C: Monitor
Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor
Glasdegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May decrease active metabolite exposure 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
Halofantrine: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects of Halofantrine. 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
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
HYDROcodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid
Indinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and moderate CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Risk D: Consider Therapy Modification
Isradipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Istradefylline. Risk C: Monitor
Ivabradine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivacaftor. Risk C: Monitor
Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Lansoprazole. Risk C: Monitor
Lapatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification
Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid
Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin: May decrease active metabolite exposure of Fexinidazole. Fexinidazole may decrease serum concentration of Lefamulin. Management: In general, avoid concomitant use of lefamulin and fexinidazole. If concomitant use is deemed necessary, monitor for reduced efficacy of both lefamulin and fexinidazole. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lemborexant. Risk X: Avoid
Lenacapavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lenacapavir. Risk X: Avoid
Leniolisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lercanidipine. Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease serum concentration of LinaGLIPtin. Risk C: Monitor
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Lonafarnib: May increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of Lonafarnib. Lonafarnib may decrease active metabolite exposure of Fexinidazole. Risk X: Avoid
Lovastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumateperone. Risk X: Avoid
Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Macitentan. Risk C: Monitor
Maraviroc: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification
Maribavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maribavir. Risk C: Monitor
MATE1/2-K Substrates (Clinically Relevant with Inhibitors): Fexinidazole may increase 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: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavacamten. Risk X: Avoid
Mavorixafor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavorixafor. Risk C: Monitor
Mefloquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mefloquine. Risk C: Monitor
Melatonin: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Melatonin. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MethylPREDNISolone. Risk C: Monitor
Mianserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mianserin. Risk C: Monitor
Midazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midazolam. Risk C: Monitor
MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification
Mirodenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mirodenafil. Risk C: Monitor
Mobocertinib: Fexinidazole may increase QTc-prolonging effects of Mobocertinib. Fexinidazole may decrease serum concentration of Mobocertinib. Risk X: Avoid
Moclobemide: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Moclobemide. Risk C: Monitor
Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor
Myelosuppressive Agents: May increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Naldemedine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naloxegol. Risk C: Monitor
Neratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Neratinib. Risk X: Avoid
Nevirapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nevirapine. Risk C: Monitor
NIFEdipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NIFEdipine. Risk C: Monitor
Nilvadipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nisoldipine. Risk X: Avoid
OAT1/3 Substrates (Clinically Relevant): Fexinidazole may increase 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 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 increase QTc-prolonging effects of OLANZapine. Fexinidazole may increase 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
Olaparib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olaparib. Risk X: Avoid
Oliceridine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olmutinib. Risk C: Monitor
Olutasidenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olutasidenib. Risk X: Avoid
Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Omaveloxolone. Risk X: Avoid
Omeprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Omeprazole. Risk C: Monitor
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
OxyCODONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of OxyCODONE. Risk C: Monitor
Paliperidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Paliperidone. Risk C: Monitor
Palovarotene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palovarotene. Risk X: Avoid
Pemigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pemigatinib. Risk X: Avoid
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pentoxifylline. Risk C: Monitor
Perampanel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Pimavanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pimavanserin. Risk X: Avoid
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase 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
Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider Therapy Modification
Pralsetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification
Praziquantel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider Therapy Modification
PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of PredniSONE. Risk C: Monitor
Pretomanid: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pretomanid. Risk X: Avoid
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
Proguanil: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Proguanil. CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Proguanil. Risk C: Monitor
Propofol: May increase arrhythmogenic effects of Fexinidazole. Propofol may increase QTc-prolonging effects of Fexinidazole. Risk X: Avoid
QT-prolonging Agents (Highest Risk): Fexinidazole may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
QT-prolonging Antidepressants (Moderate Risk): May increase QTc-prolonging effects 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
QT-prolonging Antipsychotics (Moderate Risk): May increase QTc-prolonging effects 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
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
QT-prolonging Kinase Inhibitors (Moderate Risk): May increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of QT-prolonging Kinase Inhibitors (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. Additionally, monitor for reduced efficacy of these kinase inhibitors. Risk C: Monitor
QT-prolonging Miscellaneous Agents (Moderate Risk): Fexinidazole may increase QTc-prolonging effects 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
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Specifically, concentrations of crizotinib, nilotinib, and ribociclib may be decreased. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may decrease active metabolite exposure of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Also monitor for reduced efficacy of fexinidazole, crizotinib, nilotinib, and ribociclib. Risk D: Consider Therapy Modification
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may increase QTc-prolonging effects 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
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): Fexinidazole may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of Fexinidazole. Risk X: Avoid
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may decrease active metabolite exposure of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Also monitor for reduced efficacy of fexinidazole and these CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Quizartinib: Fexinidazole may increase QTc-prolonging effects of Quizartinib. Fexinidazole may decrease serum concentration of Quizartinib. Risk X: Avoid
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramelteon. Risk C: Monitor
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramosetron. Risk C: Monitor
Ranolazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ranolazine. Risk X: Avoid
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase 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
Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor
Repaglinide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repotrectinib. Risk X: Avoid
Revumenib: Fexinidazole may increase QTc-prolonging effects of Revumenib. Fexinidazole may decrease serum concentration of Revumenib. Fexinidazole may increase active metabolite exposure of Revumenib. Risk X: Avoid
Rilpivirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rilpivirine. Risk C: Monitor
Rimegepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rimegepant. Risk X: Avoid
Ripretinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider Therapy Modification
RisperiDONE: May increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of RisperiDONE. 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. Also monitor for reduced risperidone efficacy. Risk C: Monitor
Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritlecitinib. Risk C: Monitor
Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor
Rolapitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rolapitant. Risk C: Monitor
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPINIRole. Risk C: Monitor
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPivacaine. Risk C: Monitor
Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor
Selpercatinib: Fexinidazole may increase QTc-prolonging effects of Selpercatinib. Fexinidazole may decrease serum concentration of Selpercatinib. Risk X: Avoid
Selumetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selumetinib. Risk X: Avoid
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Sertraline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sertraline. Risk C: Monitor
Sildenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sildenafil. Risk C: Monitor
Simeprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sonidegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sonidegib. Risk X: Avoid
Sparsentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sparsentan. Risk C: Monitor
Suvorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suvorexant. Risk C: Monitor
Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tadalafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tadalafil. Risk C: Monitor
Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Tasimelteon. Risk C: Monitor
Tasimelteon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor
Tazemetostat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tazemetostat. Risk X: Avoid
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase 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
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Tilidine. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. Risk C: Monitor
Tivozanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tivozanib. Risk C: Monitor
Tofacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tofacitinib. Risk C: Monitor
Tolvaptan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tolvaptan. Risk C: Monitor
TraMADol: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification
Ulipristal: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ulipristal. Risk X: Avoid
Upadacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Upadacitinib. Risk C: Monitor
Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid
Velpatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Venetoclax: CYP3A4 Inducers (Moderate) may decrease serum concentration of Venetoclax. Risk X: Avoid
Vilazodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vilazodone. Risk C: Monitor
VinCRIStine: CYP3A4 Inducers (Moderate) may decrease serum concentration of VinCRIStine. Risk C: Monitor
Voclosporin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voclosporin. Risk X: Avoid
Vonoprazan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vonoprazan. Risk X: Avoid
Vorapaxar: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vorapaxar. Risk X: Avoid
Vorasidenib: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Vorasidenib. Management: Avoid concurrent use with moderate CYP1A2 inhibitors when possible. If combined use cannot be avoided, monitor for evidence of adverse effects and adjust vorasidenib dose accordingly if necessary. Risk D: Consider Therapy Modification
Vortioxetine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vortioxetine. Risk C: Monitor
Voxelotor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification
Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxilaprevir. Risk X: Avoid
Zaleplon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zaleplon. Risk C: Monitor
Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification
Zolpidem: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zolpidem. Risk C: Monitor
Zopiclone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid
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.
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).
It is not known if fexinidazole is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, breastfeeding may continue when fexinidazole is used for the treatment of human African trypanosomiasis in lactating patients (WHO 2019).
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.
Electrolytes, leukocyte count, and LFTs at baseline and during therapy clinically as indicated; mood changes and development or worsening of psychiatric symptoms (consider increased monitoring, including hospitalization during treatment period, when using in patients with a history of psychiatric disorders); signs or symptoms of infection in patients with neutropenia.
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).
