fexinidazole is an antiprotozoal medication with a broad spectrum of activity against various parasites, including Trypanosoma brucei gambiense and Trypanosoma cruzi.
It exerts its action by disrupting the energy metabolism of the parasites, leading to their death. fexinidazole is primarily used for the treatment of sleeping sickness (African trypanosomiasis) caused by Trypanosoma brucei gambiense.
It is used for HAT hemolymphatic stage 1 and meningoencephalitic stage 2
10-Day treatment regimen
Days 1 to 4: 1800 mg (3 tab) orally every day, following
Days 5 to 10: 1200 mg (2 tab) orally every day
Dose Adjustments
Dosage Modifications
Hepatic impairment
pharmacokinetics not known; Contraindicated Renal impairment
Mild-moderate (eGFR 30 to less than 89 mL/min/1.73 m2): dose adjustment is not required
Severe (eGFR less than 30 mL/min/1.73 m2): Pharmacokinetics are not known; avoid usage
It is used for HAT hemolymphatic stage 1 and meningoencephalitic stage 2 in children aged above 6 years who weight 20 kg
Below 6 years: Safety & efficacy were not established
Above 6 years
10-Day treatment regimen
Above 20 to less than 35 kg
Days 1 to 4: 1200 mg (2 tab) orally every day, following
Days 5 to 10: 600 mg (1 tab) orally every day
More than 35 kg
Days 1 to 4: 1800 mg (3 tab) orally every day, following
Days 5 to 10: 1200 mg (2 tab) orally every day
Dose Adjustments
Dosage Modifications
Hepatic impairment
pharmacokinetics not known; Contraindicated Renal impairment
Mild-moderate (eGFR 30 to less than 89 mL/min/1.73 m2): dose adjustment is not required
Severe (eGFR less than 30 mL/min/1.73 m2): Pharmacokinetics are not known; avoid usage
There is no specific black box warning associated with fexinidazole
Contraindication/Caution:
Contraindication:
Known hypersensitivity or allergy to fexinidazole or any of its components.
Severe hepatic impairment (Child-Pugh Class C).
Co-administration with drugs that are strong CYP3A4 inhibitors or inducers.
Co-administration with drugs known to prolong the QT interval, as fexinidazole may also prolong the QT interval.
Patients with a history of or current cardiac arrhythmias or who are at risk for arrhythmias.
Patients with a history of or current severe gastrointestinal disorders.
Caution:
QT prolongation: fexinidazole has the potential to prolong the QT interval on an electrocardiogram. It should be used with caution in patients with a history of QT prolongation.
Hypersensitivity reactions: Allergic reactions, including rash, itching, and severe hypersensitivity reactions, have been reported with fexinidazole. If any signs of hypersensitivity occur, treatment should be discontinued and appropriate medical intervention initiated.
Drug interactions: fexinidazole is metabolized by CYP3A4 enzymes, so caution should be exercised when co-administering it with drugs that are strong inhibitors or inducers of CYP3A4. Drug interactions should be evaluated, and dose adjustments may be necessary.
Pregnancy & lactation: The safety and efficacy of fexinidazole in pregnant or breastfeeding women have not been established.
Comorbidities:
Hepatic impairment: fexinidazole is metabolized by the liver, so caution is advised in patients with pre-existing liver disease or impaired liver function.
Renal impairment: Although fexinidazole is primarily metabolized in the liver, the safety and efficacy of drug in the severe renal impairment or end-stage renal disease are not well established.
Cardiovascular disease: As with any antimicrobial agent, individuals with underlying cardiovascular conditions should be closely monitored during fexinidazole treatment.
Allergic conditions: Patients with a history of hypersensitivity reactions or allergies to other medications may be at an increased risk of experiencing similar reactions to fexinidazole.
Pregnancy consideration: US FDA pregnancy category: Not assigned
Lactation: Excreted into human milk: Unknown
Pregnancy category:
Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.
Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.
Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.
Category N: There is no data available for the drug under this category.
Pharmacology:
fexinidazole is an antiprotozoal medication with activity against the parasites causing African trypanosomiasis (sleeping sickness). Its pharmacology includes the following aspects:
Mechanism of Action:
fexinidazole is a nitroimidazole compound that is bioactivated within the parasites by nitroreduction. This leads to the production of reactive nitrogen species, which disrupts the DNA and other essential cellular components of the parasites, leading to their death. fexinidazole is administered orally and undergoes extensive metabolism in the liver. It is rapidly converted to its active metabolite, hydroxymethyl metabolite, which is responsible for its antiparasitic activity. The metabolites are mainly eliminated in the urine and feces.
Pharmacodynamics:
Antiprotozoal Activity: fexinidazole exhibits potent antiprotozoal activity against Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, the causative agents of human African trypanosomiasis. It acts by selectively targeting the parasites and disrupting their essential cellular processes.
Nitroreduction: fexinidazole undergoes bioactivation within the parasites through nitroreduction. This process converts the prodrug into its active form, hydroxymethyl metabolite, which is responsible for its antiparasitic activity.
DNA Damage: The activated form of fexinidazole generates reactive nitrogen species that cause DNA damage in the parasites. This DNA damage disrupts their replication and survival, leading to their death.
Targeting Parasite-Specific Pathways: fexinidazole selectively targets pathways and enzymes that are essential for the survival and growth of the trypanosomes, including electron transport chain components and enzymes involved in DNA repair.
Activity Against Different Stages: fexinidazole is effective against both the bloodstream and central nervous system stages of African trypanosomiasis. It crosses blood-brain barrier, allowing it to target the parasites in the central nervous system, which is crucial for the treatment of the disease.
Pharmacokinetics:
Absorption
fexinidazole is well absorbed after oral administration, and food does not significantly affect its absorption.
Distribution
fexinidazole and its metabolites distribute extensively throughout the body, including into tissues where trypanosomes may reside.
Metabolism
fexinidazole undergoes extensive metabolism in the liver by various enzymes, including cytochrome P450 enzymes. The primary metabolite, hydroxymethyl metabolite, has similar antiparasitic activity to the parent compound.
Elimination and excretion
fexinidazole and its metabolites are eliminated mainly through the kidneys, with a small portion excreted in the feces.
Administration:
fexinidazole is an oral medication that is typically administered in the form of tablets. The specific administration instructions may vary depending on the prescribed dose and the specific product formulation.
Generally, fexinidazole should be taken with food to enhance its absorption and minimize the risk of gastrointestinal side effects. It is important to take the medication as directed at the recommended intervals, and for the full duration of the prescribed treatment course.
Patient information leaflet
Generic Name: fexinidazole
Pronounced: (feks-in-EYE-da-zole)
Why do we use fexinidazole?
fexinidazole is primarily used for the treatment of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). It is effective against both the early-stage (hemolymphatic) and late-stage (meningoencephalitic) forms of the disease caused by Trypanosoma brucei parasites.
fexinidazole is an oral treatment option that offers advantages over traditional injectable therapies, as it is easier to administer and has a shorter treatment duration. It is an important tool in the fight against HAT, a neglected tropical disease that affects populations in sub-Saharan Africa.
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It is used for HAT hemolymphatic stage 1 and meningoencephalitic stage 2
10-Day treatment regimen
Days 1 to 4: 1800 mg (3 tab) orally every day, following
Days 5 to 10: 1200 mg (2 tab) orally every day
Dose Adjustments
Dosage Modifications
Hepatic impairment
pharmacokinetics not known; Contraindicated Renal impairment
Mild-moderate (eGFR 30 to less than 89 mL/min/1.73 m2): dose adjustment is not required
Severe (eGFR less than 30 mL/min/1.73 m2): Pharmacokinetics are not known; avoid usage
It is used for HAT hemolymphatic stage 1 and meningoencephalitic stage 2 in children aged above 6 years who weight 20 kg
Below 6 years: Safety & efficacy were not established
Above 6 years
10-Day treatment regimen
Above 20 to less than 35 kg
Days 1 to 4: 1200 mg (2 tab) orally every day, following
Days 5 to 10: 600 mg (1 tab) orally every day
More than 35 kg
Days 1 to 4: 1800 mg (3 tab) orally every day, following
Days 5 to 10: 1200 mg (2 tab) orally every day
Dose Adjustments
Dosage Modifications
Hepatic impairment
pharmacokinetics not known; Contraindicated Renal impairment
Mild-moderate (eGFR 30 to less than 89 mL/min/1.73 m2): dose adjustment is not required
Severe (eGFR less than 30 mL/min/1.73 m2): Pharmacokinetics are not known; avoid usage
