Fexinidazole

Aka: Fexinidazole

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II. Indications

  1. African Trypanosomiasis
    1. Preferred agent in stage 1 and 2 (age >=6 years and weight >20 kg)

III. Contraindications

  1. Age <6 years
  2. Weight <20 kg
  3. Unknown CSF Leukocyte count OR CSF Leukocytes >100 wbc/uL (severe Stage 2, Cerebral Trypanosomiasis)
  4. Severe hepatic Impairment or Cirrhosis
  5. Severe renal Impairment
  6. Cockayne syndrome
  7. First trimester pregnancy (may use in second or third trimester)
    1. See Safety below
    2. Avoid in West African Trypanosomiasis
    3. However, relative contraindication due to rapid lethality of East African Trypanosomiasis
      1. Start with either Fexindazole or Pentamidine in pregnancy regardless of trimester

IV. Mechanism

  1. Fexinidazole is a nitroimidazole Antiprotozoal Agent
  2. Fexinidazole is a prodrug
    1. Fexinidazole is converted to sulfoxide and sulfone active metabolites by a Parasite's nitroreductases
    2. These metabolites are toxic reactive amines, destructive to Protozoal DNA and Proteins, killing the organism

V. Medications

  1. Fexinidazole 600 mg tablets

VI. Dosing

  1. Dosing weight >=35 kg
    1. Load: 1800 mg (3 tablets) once daily for 4 days
    2. Next: 1200 mg (2 tablets) once daily for 6 days
  2. Dosing weight 20 kg to 35 kg
    1. Load: 1200 mg (2 tablets) once daily for 4 days
    2. Next: 600 mg (1 tablet) once daily for 6 days

VII. Pharmacokinetics

  1. Half-Life: 15 hours (in normal Renal Function)

VIII. Adverse Effects

  1. Serious adverse effects (uncommon)
    1. QT Interval Prolongation
    2. Neutropenia
    3. Hepatotoxicity
    4. Neuropsychiatric effects
      1. Agitation or anxiety
      2. Abnormal behavior or personality change
      3. Depressed mood or Suicidal Ideation
      4. Nightmares
      5. Hallucinations
  2. Common neurolopsychiatric adverse effects
    1. Headache
    2. Insomnia
    3. Asthenia
    4. Tremor
    5. Dizziness
  3. Common gastrointestinal adverse effects
    1. Nausea or Vomiting
    2. Decreased appetite
    3. Dyspepsia
    4. Upper Abdominal Pain
    5. Back pain
  4. Common Electrolyte abnormalities
    1. Hypocalcemia
    2. Hyperkalemia

IX. Safety

  1. Lactation
    1. May continue Lactation while taking Fexinidazole
    2. Observe infant for decreased oral intake, Vomiting or Tremor
  2. Pregnancy
    1. May use in second or third trimester
    2. First trimester use
      1. Toxicity in rat and rabbit studies have been found well above typical dosing
      2. Avoid first trimester use in West African Trypanosomiasis
      3. However, may be used first trimester in East African Trypanosomiasis (rapidly fatal)
        1. Start with either Fexindazole or Pentamidine in pregnancy regardless of trimester

X. Drug Interactions

  1. Disulfiram reaction when combined with Alcohol

XI. Resources

  1. Fexinidazole (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=74a611bc-9977-46bb-b626-0370b3031628

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