Fexinidazole

Fexinidazole is a prescription medication indicated for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitis) human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense in patients aged 6 years and older and weighing at least 20 kg.

Fexinidazole is available under the following different brand names: Fexinidazole

Common side effects of Fexinidazole include:

• indigestion
• back pain
• neck pain 
• flushing
• heartburn 
• weakness 
• nausea
• stomach pain or pressure 
• vomiting
• pins and needles or tingling 
• chest pain or pressure
• change in color vision 
• constipation
• poor night vision 
• difficulty speaking 
• drooling
• feeling of fullness or bloating 
• increased sensitivity to sunlight 
• sweating
• itching
• loss of balance control 
• twisting movement of the body
• muscle spasms or stiffness
• uncontrolled movement of the face, neck, and back

Serious side effects of Fexinidazole include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• severe dizziness
• black or tarry stools
• chest pain
• lower back pain or side pain 
• mental or mood changes
• muscle cramps or spasms 
• chills
• confusion 
• cough
• fever
• numbness and tingling around the mouth, fingertips, or feet 
• painful or difficult urination
• pale skin 
• shakiness in the arms, legs, hands, or feet 
• sore throat
• stomach pain or cramps 
• swelling of the feet or lower legs 
• trembling or shaking of the hands or feet 
• difficulty sleeping
• white spots in the mouth 
• unusual bleeding
• easy bruising
• tiredness
• weakness 
• anxiety
• blurred vision 
• rapid or shallow breathing 
• dry mouth
• fast, irregular, or pounding heartbeat
• pounding in the ears
• headache
• irritability
• nervousness 
• restlessness 
• shaking
• personality changes 
• depression
• loss of appetite 
• hallucination
• thoughts of self-harm 
• difficulty concentrating 
• fainting
• nightmares

Rare side effects of Fexinidazole include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 600 mg

African trypanosomiasis

Adult dosage

• 10-Day regimen
  • Days 1-4: 1800 mg (3 tablets) orally once a day, then
  • Days 5-10: 1200 mg (2 tablets) orally once a day

Pediatric dosage

• Children younger than 6 years: Safety and efficacy not established
• Children aged 6 years and older
• 10-Day regimen
  • Children weighing 20 kg and more to less than 35 kg
    • Days 1-4: 1200 mg (2 tablets) orally once a day, then
    • Days 5-10: 600 mg (1 tablet) orally once a day
  • Children weighing 35 kg and more
    • Days 1-4: 1800 mg (3 tablets) orally once a day, then
    • Days 5-10: 1200 mg (2 tablets) orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Fexinidazole has severe interactions with the following drugs:
  • fezolinetant
  • lonafarnib
  • mavacamten
• Fexinidazole has serious interactions with at least 471 other drugs
• Fexinidazole has moderate interactions with at least 89 other drugs
• Fexinidazole has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to fexinidazole and/or any nitroimidazole-class drug (eg, metronidazole, tinidazole)
• Patients with Cockayne syndrome
• Hepatic impairment

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Fexinidazole?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Fexinidazole?”

Cautions

• Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes reported after initiation of metronidazole, another nitroimidazole drug, structurally related to benznidazole in patients with Cockayne syndrome
• Adults treated with fexinidazole reported a higher percentage of CNS and psychiatric-related adverse reactions compared with nifurtimox-eflornithine combination therapy (NECT); consider alternant therapy or increase monitoring with current or history of psychiatric disorders, or if such adverse reactions occur
• Neutropenia reported; avoid concomitant use with drugs that cause neutropenia; monitor for neutropenia, fever, or signs of infection; treat promptly if symptoms occur
• Monitor for elevated liver transaminases
• Severe second-stage HAT
  • Decreased efficacy observed in patients treated with fexinidazole compared with NECT-treated patients in a randomized, comparative open-label study in the subgroup of patients with severe second-stage disease (Colony stimulating factor-white blood cells of more than 100 cells/mcL at baseline)
  • For severe second-stage HAT, consider fexinidazole only if there are no other available treatment options
• QT prolongation
  • Shown to prolong the QT interval in a concentration-dependent manner (QTcF interval average increase of 19 msec)
  • Avoid coadministration with other drugs known to prolong QT interval or drugs that increase systemic exposure to fexinidazole’s active metabolite
  • Avoid use in QTcF interval above 470 msec
  • History of torsade de pointes, congenital long QT syndrome, cardiac arrhythmias, uncompensated heart failure, or family history of sudden death
• Uncorrected hypokalemia
• Drug interaction overview
  • Inhibits CYP isoenzymes 3A4, 1A2, and 2C19
  • Induces CYP2B6
  • Inhibits transporters OCT2, OAT1, OAT3, MATE1, and MATE2-K
  • Substrate of multiple CYP450 enzymes; these enzymes are involved in the metabolism of fexinidazole to its pharmacologically active M1 and M2 metabolites
  • CYP450 inducers
    • Avoid coadministration with drugs that are CYP450 inducers
    • These drugs may significantly increase plasma concentrations of fexinidazole’s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2)
    • M2 plasma concentrations associated with increased QT prolongation risks
  • CYP450 inhibitors
    • Avoid coadministration; if unavoidable, monitor for lack of efficacy of fexinidazole owing to the potential for decreased plasma concentrations of active metabolites
    • Multiple CYP450 enzymes are involved in fexinidazole metabolism to its pharmacologically active metabolites
• Drugs that prolong QT interval and/or induce bradycardia
  • Avoid coadministration with other drugs known to prolong QT interval, those that block cardiac potassium channels, and/or those that induce bradycardia
  • If treated with or need to on drugs known to prolong QTcF interval or to induce bradycardia, either do not initiate therapy with fexinidazole until such drugs are eliminated from the body (allow washout period of 5 half-lives) or do not start such drugs until Fexinidazole is eliminated (allow washout period of 7 days)
• Alcohol
  • Avoid alcohol consumption during treatment and for at least 48 hours after last dose
  • Nitroimidazole-class drugs may cause a disulfiram-like reaction characterized by flushing, rash, weakness, abdominal cramps, nausea, vomiting, and headache when coadministered with alcohol
• Disulfiram
  • Avoid use in patients who have taken disulfiram within the last 2 weeks
  • Psychotic reactions were reported in patients who were concurrently taking disulfiram and nitroimidazole drugs
• Substrates of CYP3A4
  • Avoid coadministration
  • May increase the risk for adverse effects by increasing the concentration of CYP3A4 substrates owing to fexinidazole inhibiting CYP3A4
• Substrates of CYP1A2 or CYP2C19
  • Monitor for adverse effects of CYP1A2/CYP2C19 substrates
  • Increased risk for adverse reactions with substrates owing to CYP1A2/CYP2C19 inhibition by fexinidazole
• Substrates of CYP2B6
  • Avoid coadministration; if unavoidable, monitor for lack of efficacy
  • May decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6
• Substrates of OAT2, OAT1, OAT3, MATE1, and MATE2-K transporters
  • Avoid coadministration; if unavoidable, monitor for adverse reactions
  • Increased risk for adverse reactions associated with increased concentrations of transporter substrates owing to inhibition of these transporters by fexinidazole
• Herbals and supplements
  • Avoid concomitant use of herbal medicines and supplements during treatment
  • Potential for pharmacodynamic interactions and/or toxicities between fexinidazole and herbal medicines and supplements

Pregnancy and Lactation

• Available data from clinical trials with fexinidazole use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects or miscarriage
• Clinical considerations
  • There are risks to the mother and fetus associated with untreated HAT due to T brucei gambiense during pregnancy
  • Disease progression may occur during pregnancy
  • Pregnant women should be treated for HAT during pregnancy to prevent vertical transmission
  • For timing of treatment during pregnancy, consider the benefits to the mother and the potential risks to the fetus
• Lactation
  • Data are unavailable on the presence of human milk or the effect on milk production
  • There are no reports of adverse effects to breastfed children associated with fexinidazole exposure through breastmilk based on a limited number of reported cases
  • Fexinidazole is present in rat milk; when a drug is present in animal milk, it is likely to be present in human milk