Fexinidazole Disease Interactions

Fexinidazole is contraindicated in patients with liver dysfunction since it is extensively metabolized by the liver. However, the pharmacokinetics of fexinidazole in patients with liver dysfunction is unknown. Liver-related laboratory tests should be evaluated at the start and during therapy with fexinidazole. Patients who develop abnormal liver-related laboratory tests during treatment with fexinidazole should be monitored.

In a clinical trial, adult patients treated with fexinidazole reported a higher percentage of CNS and psychiatric-related side effects than those treated with nifurtimox-eflornithine combination therapy (NECT). Increased incidence of insomnia, headache, and tremor was observed in patients treated with fexinidazole compared to NECT. In the same trial, side effects signifying mood changes and psychiatric disorders (e.g., agitation, anxiety, abnormal behavior, depression, nightmares, hallucination, personality change) were more common with fexinidazole compared to NECT; suicidal ideation was also seen with fexinidazole. In patients with current or history of psychiatric disorders, alternative therapy or increased monitoring of the patient (including hospitalization) should be considered.

Fexinidazole prolongs the QT interval in a concentration-dependent manner; treatment with fexinidazole caused an average increase of 19 msec in the QTcF interval (corrected QT interval by Fridericia). Fexinidazole should be avoided in patients who have: QTcF interval greater than 470 msec; history of torsade de pointes, congenital long QT syndrome, cardiac arrhythmias, uncompensated heart failure, or family history of sudden death; uncorrected hypokalemia.

The use of fexinidazole should be avoided in patients with severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2); the pharmacokinetics of fexinidazole in patients with severe renal dysfunction is unknown. No dosage adjustment is necessary for patients with mild to moderate renal dysfunction.

Nitroimidazoles (e.g., metronidazole, tinidazole, fexinidazole, secnidazole) may inhibit alcohol dehydrogenase and occasionally precipitate a disulfiram-like reaction in patients who consume alcohol while being treated. Symptoms may include abdominal cramps, nausea, vomiting, headache, flushing, rash, weakness, diarrhea, abdominal pain, dizziness, sweating, and hypotension. Patients should be instructed to avoid alcohol-containing products during nitroimidazole therapy and for at least 48 hours (fexinidazole, secnidazole) to 72 hours (metronidazole, tinidazole) after the last dose. Therapy with nitroimidazoles should be administered cautiously in patients who might be prone to acute alcohol intake. An alternative therapy may be appropriate.