fezolinetant

Action and Spectrum

Actions and Spectrum: 

fezolinetant is being developed as a non-hormonal treatment for menopausal vasomotor symptoms (commonly known as hot flashes or flushes). It is a selective antagonist of the neurokinin-3 (NK3) receptor. 

The NK3 receptor is a receptor found in the brain and other tissues. It regulates the release of a neurotransmitter called neurokinin B (NKB), which regulates body temperature, among other functions. By antagonizing the NK3 receptor, fezolinetant is thought to modulate the release of NKB and subsequently reduce the frequency and severity of hot flashes experienced by menopausal women. 

The spectrum of activity refers to the range of conditions or symptoms that a drug can effectively treat. fezolinetant’s primary focus is on alleviating menopausal vasomotor symptoms. However, additional studies may explore its potential benefits in other areas, as the neurokinin system involves various physiological processes throughout the body. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Diarrhea (3.9%) 

Back pain (3%) 

Elevated hepatic transaminase (2.3%) 

Abdominal pain (4.3%) 

Insomnia (3.9%) 

Hot flush (2.5%) 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: fezolinetant should not be used in individuals with known hypersensitivity or allergy to the drug or its components. Allergic reactions can range from mild to severe and may include symptoms such as rash, itching, swelling, or difficulty breathing. 
• Pregnancy and lactation: The safety of fezolinetant during pregnancy and breastfeeding has not been established. It is essential to consult with a healthcare professional if you are pregnant, planning to become pregnant, or breastfeeding before considering using fezolinetant. 
• Severe hepatic impairment: fezolinetant may be contraindicated or require dose adjustment in individuals with severe liver impairment. The drug’s metabolism and elimination may affect such individuals, potentially leading to increased drug levels and adverse effects. 
• Severe renal impairment: fezolinetant may be contraindicated or require dose adjustment in individuals with severe kidney impairment. Impaired renal function can affect the clearance of the drug from the body, potentially leading to increased drug levels and adverse effects. 
• Concurrent use with certain medications: fezolinetant may interact with other medications, potentially leading to adverse effects or reduced efficacy.  

Caution: 

• Drug interactions: fezolinetant may interact with other medications, including prescription, over-the-counter, and herbal products. These interactions can affect the efficacy or safety of fezolinetant or other drugs.  
• Hepatic impairment: fezolinetant may require caution or dose adjustment in individuals with mild to moderate hepatic impairment. Liver function may impact the metabolism and elimination of fezolinetant, and dosage adjustments may be necessary to maintain safety and effectiveness. 
• Renal impairment: fezolinetant may require caution or dosage adjustment in individuals with renal impairment. Impaired kidney function can affect the clearance of fezolinetant from the body, and dose modification may be necessary to avoid adverse effects. 
• Cardiovascular conditions: fezolinetant may have effects on blood pressure or heart rate. Individuals with pre-existing cardiovascular conditions, such as hypertension or a history of heart disease, may require caution when using fezolinetant. Monitoring of cardiovascular parameters may be necessary during treatment. 
• Central nervous system (CNS) effects: fezolinetant may have CNS-related side effects, such as dizziness or drowsiness. Caution should be exercised while performing tasks that require alertness, such as driving or operating machinery, primarily until the individual’s response to the medication is known. 
• Psychiatric conditions: fezolinetant may affect mood or mental state. Individuals with pre-existing psychiatric conditions should be closely monitored during treatment with fezolinetant. 
• Allergic reactions: Although rare, fezolinetant may cause hypersensitivity or allergic reactions. Suppose any signs of an allergic reaction occur, such as rash, itching, swelling, or difficulty breathing. In that case, immediate medical attention should be sought. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is 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 available 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

Pharmacology: 

fezolinetant is a selective antagonist of the neurokinin-3 (NK3) receptor. The NK3 receptor is a receptor found in the brain and other tissues. It regulates various physiological processes, including releasing neurokinin B (NKB) neurotransmitters. NKB is thought to play a role in modulating body temperature, among other functions. 

By selectively blocking the NK3 receptor, fezolinetant modulates the NKB signaling pathway. This modulation is believed to contribute to the potential therapeutic effects of fezolinetant in treating menopausal vasomotor symptoms, such as hot flashes. It is thought that fezolinetant’s antagonism of the NK3 receptor reduces the release of NKB and helps to alleviate the frequency and severity of hot flashes experienced by menopausal women. 

Pharmacodynamics: 

fezolinetant is an investigational drug, and its pharmacodynamics are still being studied. However, based on available preclinical and early clinical data, it is believed that fezolinetant exerts its pharmacodynamic effects by selectively antagonizing the neurokinin-3 (NK3) receptor.  

The NK3 receptor is a receptor found in the brain and other tissues. It regulates various physiological processes, including releasing neurokinin B (NKB) neurotransmitters. NKB is thought to play a role in modulating body temperature, among other functions. 

fezolinetant selectively blocks the NK3 receptor, thereby modulating the NKB signaling pathway. This modulation is believed to contribute to the potential therapeutic effects of fezolinetant in treating menopausal vasomotor symptoms, such as hot flashes or hot flashes. 

Pharmacokinetics: 

Absorption 

fezolinetant’s absorption profile, including its bioavailability and the rate at which it reaches the systemic circulation, would need to be determined through clinical studies. 

Distribution 

The drug’s lipophilicity, protein binding, and tissue permeability can influence its distribution. Fezolinetant’s specific distribution characteristics are not currently known. 

Metabolism 

Metabolism primarily occurs in the liver, although other tissues may also contribute. The specific enzymes involved in fezolinetant metabolism and the resulting metabolites are currently unknown. 

Elimination and Excretion 

The primary route of elimination is through the kidneys via urine (renal elimination). However, drugs can also be eliminated through feces, breath, sweat, or other routes. The elimination half-life reflects the time required for the concentration of a drug in the body to be reduced by half. 

Adminstartion

Administration: 

Oral Administration 

• fezolinetant is taken orally. 
• It may be taken with or without food. 
• It is advisable to administer the medication at approximately the same time each day for consistent dosing. 

Tablet Administration: 

• The tablet should be swallowed whole with liquids. 
• Do not cut, crush, or chew the tablet. It should be taken as a whole.

Missed Dose: 

• If a dose of fezolinetant is missed or not taken at the usual time, it should be administered as soon as possible unless it is less than 12 hours before the next scheduled dose. 
• Return to the regular dosing schedule the following day if a dose is missed.

Storage: 

• fezolinetant should be stored at a temperature of 20-25ºC (68-77ºF). 
• Excursions from 15-30ºC (59-86ºF) are permitted, which means the medication can be exposed to temporary temperature fluctuations within that range. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fezolinetant 

Why do we use fezolinetant? 

fezolinetant is used to treat menopausal vasomotor symptoms, such as hot flashes and night sweats, in women. Vasomotor symptoms are expected during menopause, and they can significantly impact the quality of life of affected women. fezolinetant is being developed as a non-hormonal alternative to traditional hormone therapy, the current standard of care for treating these symptoms.