Drug reference

fexinidazole

Nitroimidazole · Antiprotozoal

NitroimidazoleAntiprotozoal

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

—

not curated

Mechanism

Fexinidazole is a prodrug activated by a bacterial-like type 1 nitroreductase (NTR1) in trypanosomatids, which uses NADH as a reductive cofactor to perform 2e- electron oxidation reactions. This process forms a highly reactive unsaturated open-chain nitrile, which is believed to cause cellular toxicity by interacting with multiple cellular targets, including DNA modification. This mechanism provides species-selective toxicity as no mammalian homolog of NTR1 exists.

Indications

Early-stage West African (Gambian) trypanosomiasisUncomplicated late-stage West African (Gambian) trypanosomiasis (adults and children ≥6 years and ≥20 kg)First-stage T. b. gambiense HATNonsevere second-stage T. b. gambiense HAT (<100 leukocytes/μL in CSF)Severe second-stage T. b. gambiense HAT (≥100 leukocytes/μL in CSF, with lower cure rate)First-stage T. b. rhodesiense HAT (alternative treatment)Second-stage T. b. rhodesiense HAT (alternative treatment)

Dosing

Pediatric: 20–34 kg: 1200 mg for 4 days, followed by 600 mg for 6 days (oral, with food)
Renal adjustment: Contraindicated in advanced renal failure.

Pharmacokinetics

Peak effect

Parent compound peak plasma levels rapid; sulfoxide peak at 2–5 h; sulfone peak at 18–24 h.

Bioavailability

Increased 4- to 5-fold with food

Metabolism

Rapidly metabolized to sulfoxide (tmax = 2–5 h) and sulfone (tmax = 18–24 h); metabolites are responsible for most in vivo trypanosomatid killing.

Excretion

Almost entirely extrarenal (renal clearance of 1.2–6.0 mL/h vs. oral clearance of 80 L/h)

Contraindications

Hepatic insufficiency
Increased risk of QT interval prolongation
Children <6 years and/or weighing <20 kg

Side effects

Common

Headache (35%)Tremor (22%)Dizziness (19%)Vomiting (28%)Nausea (26%)Decreased appetite (21%)InsomniaAnxietyVomitingHeadacheNeuropsychiatric disorders (e.g., insomnia, anxiety, agitation)

Drug interactions

Nifurtimox

Moderate

Textbook

Resistance generated to one drug in the field (e.g., through changes in NTR1 expression levels) could lead to clinical resistance to both compounds.

Monitor for signs of treatment failure. This underscores a vulnerability in current treatment strategy. The text implies shared resistance is a concern for treatment strategy, not a direct drug-drug adverse effect in a patient. So, this should be noted for physicians when choosing treatment options, but it is not a traditional drug-drug interaction in the sense of one modifying the effects of the other in the body of the patient.

Source: G&G 14e · p1309-1324