Fezolinetant

Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that blocks neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center. Fezolinetant has high affinity for the NK3 receptor (Ki value of 19.9 to 22.1 nmol/L), which is more than 450-fold higher than binding affinity to NK1 or NK2 receptors.

Treatment with fezolinetant did not show any clear trends in sex hormones measured in menopausal women.

• Vasomotor Symptoms of Menopause: Used for treatment of moderate to severe hot flashes and night sweats due to menopause.

Other genito-urinary preparations

NK3 Receptor Antagonist

Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that blocks neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center. Fezolinetant has high affinity for the NK3 receptor.

Fezolinetant blocks NK3 receptors to prevent NKB action on KNDy neurons, thereby modulating neuronal activity in the thermoregulatory center and reducing hot flashes.

Adult Dose (Oral):

• One 45 mg tablet orally once daily with or without food.
• Swallow whole with liquids; do not cut, crush, or chew tablets.
• Administer at about the same time each day.

Take one 45 mg tablet orally once daily. Swallow whole with liquids; do not cut, crush, or chew. Take at about the same time each day.

If a dose is missed, administer as soon as possible, unless there is less than 12 hours before the next scheduled dose; in that case, skip the missed dose and return to the regular schedule the following day.

Common Side Effects:

• Abdominal pain
• Diarrhea
• Difficulty sleeping
• Back pain
• Hot flashes

Signs of Liver Problems (Stop Fezolinetant):

• Nausea
• Vomiting
• Itching
• Yellowing of eyes or skin (jaundice)
• Pale feces
• Dark urine
• Pain in right upper abdomen

Precautions:

• Hepatic Transaminase Elevation and Hepatotoxicity: Elevations >3 times ULN occurred in clinical trials; perform hepatic lab tests prior to initiation; do not start if ALT or AST >=2 × ULN or total bilirubin >=2 × ULN; perform follow-up hepatic lab tests monthly for first 3 months, at 6 months, and 9 months after initiation.

Contraindications:

• Known cirrhosis
• Severe renal impairment or end-stage renal disease
• Concomitant use with CYP1A2 inhibitors

Drug Interactions:

• CYP1A2 Inhibitors (weak, moderate, or strong): Increase plasma Cmax and AUC of Fezolinetant; contraindicated with CYP1A2 inhibitors.

Food Interactions: May be taken with or without food. Caution with alcohol.

Use in Pregnancy: No data on use in pregnant women; caution required.

Use in Lactation: No data on presence in human milk; caution required.

Pediatric Use: Safety and efficacy not established in individuals less than 18 years.

Geriatric Use: Not sufficient numbers of geriatric women involved in clinical trials.

Renal Impairment: Contraindicated in patients with severe renal impairment or ESRD.

Hepatic Impairment: Contraindicated in patients with cirrhosis; caution in other liver diseases.

Overdose: Discontinue Fezolinetant therapy and institute appropriate symptomatic care.

Storage: Store below 30 degree C. Keep away from light and out of reach of children.

Fezolinetant