FEXINIDAZOLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FEXINIDAZOLE (FEXINIDAZOLE).
Fexinidazole is a nitroimidazole derivative that enters the parasite and inhibits DNA synthesis by forming reactive metabolites, leading to cell death. It is active against Trypanosoma brucei gambiense.
| Metabolism | Primarily hepatic via oxidation and reduction, involving CYP450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4) and aldehyde oxidase. |
| Excretion | Primarily renal (60-70% unchanged), with 20-30% biliary/fecal. |
| Half-life | Approximately 8-12 hours in adults; prolonged in hepatic impairment. |
| Protein binding | 20-30% bound to albumin. |
| Volume of Distribution | 0.6-0.8 L/kg, indicating wide tissue distribution. |
| Bioavailability | Oral: 85-95%. |
| Onset of Action | Oral: 1-2 hours; IV: 15-30 minutes. |
| Duration of Action | 12-24 hours, supporting twice-daily dosing. |
500 mg orally twice daily for 10 days for trichomoniasis; 2 g orally single dose for giardiasis.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: not recommended; hemodialysis: administer after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Trichomoniasis: 15 mg/kg/day orally divided into 2 doses for 10 days; Giardiasis: 30 mg/kg orally single dose (max 2 g). |
| Geriatric use | Reduce dose by 50% due to age-related decline in renal function; monitor for neurotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FEXINIDAZOLE (FEXINIDAZOLE).
| Breastfeeding | No human data available; fexinidazole and its metabolites are likely excreted into breast milk based on animal studies. M/P ratio unknown. Breastfeeding is contraindicated during therapy and for 48 hours after last dose. |
| Teratogenic Risk | Fexinidazole is contraindicated in pregnancy due to teratogenicity observed in animal studies (skeletal and visceral malformations). First trimester exposure carries highest risk. Second and third trimester risks include potential fetal growth restriction and central nervous system effects. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to fexinidazole or any excipient.","Concurrent use of strong CYP3A4 inducers (e.g., rifampin, carbamazepine).","Lactation: discontinue breastfeeding during treatment."]
| Precautions | ["Hepatotoxicity: monitor liver enzymes at baseline and during treatment.","QT interval prolongation: caution in patients with cardiac conditions or taking QT-prolonging drugs.","Neuropsychiatric effects: monitor for confusion, agitation, or seizures.","Embryotoxicity: avoid use in pregnancy unless benefit outweighs risk."] |
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| Fetal Monitoring |
| Monitor liver function (ALT, AST, bilirubin), complete blood count, ECG (QTc prolongation risk), and psychiatric symptoms. Fetal ultrasound for growth and anatomy if exposure occurs. |
| Fertility Effects | Reversible fertility impairment in animal studies (reduced spermatogenesis and sperm motility). Human data lacking; potential for temporary reduction in fertility in both males and females. |