Veozah (fezolinetant)
Menopausal Symptoms Suppressant - Neurokinin Receptor Antago Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Fezolinetant is a small molecule neurokinin 3 (NK3) receptor antagonist.
Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that blocks neurokinin B (NKB) binding on kisspeptin/neurokinin B/dynorphin (KNDy) neurons. The thermoregulatory center in the hypothalamus is innervated by KNDy neurons; these neurons are stimulated by the neuropeptide NKB, acting at NK3 receptors, and inhibited by estrogen. During menopause, declining concentrations of estrogen alter the activation of KNDy neurons, resulting in hypertrophy of the neurons and dysregulation of the thermoregulatory center.
By antagonizing NKB/NK3-mediated signaling, fezolinetant modulates KNDy neuronal activity in the thermoregulatory center. Fezolinetant exhibits over 450 times greater affinity for NK3 receptors than neurokinin 1 (NK1) or neurokinin 2 (NK2) receptors.
In healthy women, fezolinetant plasma concentrations increase proportionally with daily doses of 20 to 60 mg, reaching steady-state after 2 doses with minimal accumulation. The median time to reach peak plasma concentrations is 1.5 hours. Food does not significantly affect fezolinetant pharmacokinetics.
The plasma protein binding of fezolinetant is 51%. The effective half-life of fezolinetant is 9.6 hours. Fezolinetant is primarily metabolized by cytochrome P-450 (CYP)1A2, and to a lesser extent by CYP2C9 and CYP2C19.
The major metabolite, ES259564, is 20 times less potent than fezolinetant. Most of the dose is excreted in the urine (76.9%), with a smaller amount in feces (14.7%).
USES: This medication is used to help reduce certain symptoms of menopause (such as hot flashes, night sweats). Fezolinetant works by blocking a certain chemical (neurokinin B-NKB) in the temperature control area of the brain that can cause hot flashes and night sweats.
Generic name: fezolinetant
Drug class: Menopausal Symptoms Suppressant - Neurokinin Receptor Antago
Therapeutic class: Endocrine
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Veozah:
- Vasomotor Symptoms Associated With Menopause
Dosing
No dosing information is available for this tab.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Veozah 45 Mg Tablet | Maintenance | Take 1 tablet (45 mg) by oral route once daily. |
No dosing information is available for this tab.
Drug interactions
Fezolinetant is a substrate of cytochrome P-450 (CYP)1A2. Fezolinetant and its metabolite ES259564 do not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, and do not induce CYP1A2, CYP2B6, and CYP3A4.
Fezolinetant is not a substrate or inhibitor of P-glycoprotein (P-gp). ES259564 is a substrate of P-gp, but not an inhibitor of P-gp. Fezolinetant and ES259564 are not substrates of breast cancer resistance protein (BCRP) and organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1, OATP1B3). ES259564 is not a substrate of organic anion transporters 1 and 3 (OAT1, OAT3), organic cation transporter 2 (OCT2), and multidrug and toxin extrusion proteins 1 and 2-K (MATE1, MATE2-K).
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Fezolinetant/Cyp1a2 Inhibitors
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of fezolinetant.(1-4)
CLINICAL EFFECTS: Concurrent use of a CYP1A2 inhibitor may increase levels of and adverse effects from fezolinetant.(1-4)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Recommendations for concurrent use of fezolinetant with CYP1A2 inhibitors differ in different regions. The US manufacturer of fezolinetant states that concurrent use with strong, moderate, and weak CYP1A2 inhibitors is contraindicated.(1) The Australian, Canadian, and UK manufacturers of fezolinetant state that concurrent use with strong and moderate CYP1A2 inhibitors is contraindicated, while weak CYP1A2 inhibitors are not predicted to cause clinically relevant changes in fezolinetant exposure.(2-4)
DISCUSSION: In a study, fluvoxamine, a strong CYP1A2 inhibitor, increased fezolinetant maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 840%, respectively. Mexiletine (400 mg every 8 hours), a moderate CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 40% and 360%, respectively. Cimetidine (300 mg every 6 hours), a weak CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 30% and 100%, respectively.(1) Strong CYP1A2 inhibitors linked to this monograph include angelica root, ciprofloxacin, enasidenib, enoxacin, fluvoxamine, and rofecoxib. Moderate CYP1A2 inhibitors linked to this monograph include capmatinib, centanafadine, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine. Weak CYP1A2 inhibitors linked to this monograph include acyclovir, allopurinol, artemisinin, belumosudil, caffeine, cannabidiol, cimetidine, curcumin, dan-shen, deferasirox, disulfiram, Echinacea, famotidine, ginseng, norfloxacin, obeticholic acid, parsley, piperine, propafenone, propranolol, ribociclib, simeprevir, thiabendazole, ticlopidine, triclabendazole, valacyclovir, verapamil, and zileuton.(5-7)
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known cirrhosis.
*Severe renal impairment or end-stage renal disease.
*Concomitant use with cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors.
- Pregnancy
- Disease of liver
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Adverse reactions
The most common adverse reactions with fezolinetant (reported in at least 2% of patients and more than placebo) are abdominal pain, diarrhea, insomnia, back pain, hot flush, and elevated hepatic transaminases.
Less Frequent
- Increased alanine transaminase
- Increased aspartate transaminase
Rare or Very Rare
- Drug-induced hepatitis
More Frequent
- Acute abdominal pain
- Back pain
- Diarrhea
- Insomnia
Less Frequent
- Drug-induced hot flash
Precautions
No enhanced messaging available.
There is no experience with fezolinetant in individuals younger than 18 years of age.
There are no data on fezolinetant use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, embryolethality, but no teratogenicity, was observed at doses above the human therapeutic dose.
There are no data on the presence of fezolinetant in human milk, the effects on the breastfed child, or the effects on milk production.
The manufacturer makes no specific dosage recommendations for geriatric patients.
There is not enough data to assess if women over 65 years of age respond differently to fezolinetant than younger women.
ICD codes
| Code | Type | Description |
|---|---|---|
| Vasomotor symptoms associated with menopause | ||
| N95.1 | ICD10CM | Menopausal and female climacteric states |
| N95.9 | ICD10CM | Unspecified menopausal and perimenopausal disorder |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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