Fezolinetant
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alen Antony Pathil, M.D.[2]
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NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
Overview
Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that is FDA approved for the treatment of moderate to severe vasomotor symptoms due to menopause.. Common adverse reactions include abdominal pain, diarrhea, insomnia, back pain, hot flush, and hepatic transaminase elevation..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Fezolinetant is used to treat moderate and severe vasomotor symptoms due to menopause.
The recommended dosage is 45 mg administered orally as a tablet, once daily with or without meal. Always perform blood work to evaluate for hepatic impairment/failure prior to initiation of the treatment and follow up with blood workup every 3 months, 6 months and 9 months after initiating the therapy.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Fezolinetant FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
- Known history of cirrhosis
- Known history of Severe renal impairment or end-stage renal disease
- Concomitant use with CYP1A2 inhibitors
Warnings
Elevation of Hepatic transaminases
In three clinical trials, there has been elevation of transaminases three times the upper limit observed in 2.3% [exposure adjusted incidence rate (EAIR) of 2.7 per 100 person-years] of women receiving VEOZAH and 0.9% (EAIR of 1.5 per 100 person-years) women receiving placebo.
Do not start VEOZAH if concentration of ALT or AST is equal to or exceeds two times the Upper limit or if the total bilirubin is elevated which is equal to or exceeds two times the upper normal limit for the evaluating laboratory.
Evaluate the serum AST ALT and bilirubin level at 3 months, 6 months, and 9 months after initiating the therapy and also when the patient develops symptoms of hepatic injury (like nausea, vomiting, or yellowing of the skin or eyes).
Adverse Reactions
Clinical Trials Experience
In a double blinded 52-week trial, 602 women were taking VEOZAH 45mg and 610 received placebo and at least 2% were reported in VEOZAH 45mg and greater than placebo.
Among which the adverse effects were Abdominal pain was 4.3%, Diarrhea was 3.9%, Insomnia was 3.9%, Back pain was 3.0%, Hot flush 2.5% and Hepatic transaminase elevation was 2.3%.
Postmarketing Experience
There is limited information regarding Fezolinetant Postmarketing Experience in the drug label.
Drug Interactions
VEOZAH is contraindicated in individuals using CYP1A2 inhibitors because concomitant use of VEOZAH with drugs that are weak, moderate, or strong CYP1A2 inhibitors, increase the plasma concentration of VEOZAH.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
no data on VEOZAH use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Fezolinetant in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Fezolinetant during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Fezolinetant in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Fezolinetant in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Fezolinetant in geriatric settings.
Gender
There is no FDA guidance on the use of Fezolinetant with respect to specific gender populations.
Race
There is no FDA guidance on the use of Fezolinetant with respect to specific racial populations.
Renal Impairment
VEOZAH is contraindicated in individuals with severe (eGFR 15 to less than 30 mL/min/1.73 m2) renal impairment or end-stage renal disease (eGFR less than 15 mL/min/1.73 m2) .
Dosage adjustment is not required for mild and moderate renal impairement.
Hepatic Impairment
Child-Pugh Class A or B hepatic impairment increased the exposure of VEOZAH, however VEOZAH has not been studied in individuals with Child-Pugh Class C hepatic impairment.
VEOZAH is contraindicated in individuals with cirrhosis
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Fezolinetant in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Fezolinetant in patients who are immunocompromised.
Administration and Monitoring
Administration
VEOZAH (fezolinetant) is administered orally once daily as a single tablet of 45 mg with or without meal.
If a dose of VEOZAH is missed or not taken at the usual time, administer the missed dose as soon as possible, unless there is less than 12 hours before the next scheduled dose and return to the regular schedule the following day.
Monitoring
Serum AST, ALT and Bilirubin should be evaluated prior to initiating this medication to evaluate for hepatic injury/failure.
During the treatment phase using VEOZAH, follow-up bloodwork is performed at 3 months, 6 months, and 9 months after initiation of therapy and when symptoms (such as nausea, vomiting, or yellowing of the skin or eyes) suggest liver injury.
IV Compatibility
There is limited information regarding the compatibility of Fezolinetant and IV administrations.
Overdosage
There is limited information regarding Fezolinetant overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Fezolinetant Pharmacology in the drug label.
Mechanism of Action
VEOZAH 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.
Structure
The chemical name of fezolinetant is (4-Fluorophenyl)[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]methanone having a molecular formula of C16H15FN6OS and a molecular weight of 358.39.
Pharmacodynamics
Transient decrease of luteinizing hormone (LH) levels was observed at peak concentrations of fezolinetant.
Pharmacokinetics
- The median (range) time to reach fezolinetant Cmax is 1.5 (1 to 4) hours in healthy women.
No clinically significant differences in fezolinetant pharmacokinetics were observed following administration with a high-calorie, high-fat meal containing approximately 1000 calories
- The mean apparent volume of distribution of fezolinetant is 189 L. The plasma protein binding of fezolinetant is 51% and the blood-to-plasma ratio is 0.9.
- The effective half-life (t1/2) of fezolinetant is 9.6 hours in women with vasomotor symptoms.
- Fezolinetant is primarily metabolized by CYP1A2 and to a lesser extent by CYP2C9 and CYP2C19 with the major metabolite ES259564, is identified in plasma and is approximately 20-fold less potent than the parent.
- 76.9% of the dose was excreted in urine (1.1% unchanged) and 14.7% in feces (0.1% unchanged) following oral administration of fezolinetant.
Nonclinical Toxicology
There is limited information regarding Fezolinetant Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Fezolinetant Clinical Studies in the drug label.
How Supplied
VEOZAH (fezolinetant) 45 mg tablets are supplied as round, light red, film-coated tablets, debossed with the Astellas logo and ‘645’ on the same side.
VEOZAH tablets are available in the following package sizes:
- Bottles of 30 tablets with child resistant closure and desiccant
- Bottles of 90 tablets with child resistant closure and desiccant
Storage
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F)
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Fezolinetant Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Fezolinetant interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
VEOZAH
Look-Alike Drug Names
There is limited information regarding Fezolinetant Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.