Veozah From Astellas Pharma

The FDA has approved fezolinetant oral tablets (Veozah) from Astellas Pharma for the management of moderate to severe vasomotor symptoms (VMSs) due to menopause.¹ Characterized as hot flashes and/or night sweats, VMSs are common during menopause and affect an estimated 60% to 80% of American women.

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Fezolinetant is a nonhormonal neurokinin 3 receptor antagonist. Before menopause, estrogen and neurokinin B (NKB) levels are balanced to regulate the body’s temperature control center in the brain. As estrogen levels decline during menopause, an imbalance occurs and can lead to VMSs. VMSs are the most common reason for women seeking treatment during menopause.²

PHARMACOLOGY AND PHARMACOKINETICS

Fezolinetant blocks NKB binding on the kisspeptin/NKB/dynorphin neuron to regulate neuronal activity in the thermoregulatory center. The median time to maximum plasma concentration is 1.5 hours after oral administration, and steady-state plasma concentrations are reached after 2 doses. Fezolinetant displays a half-life of 9.6 hours and is primarily metabolized by cytochrome P450 (CYP) 1A2, with metabolism to a lesser extent by cytochrome CYP2C9 and CYP2C19. Its major metabolite has been identified in plasma and is approximately 20-fold less potent than fezolinetant.¹

DOSAGE AND ADMINISTRATION

Before beginning treatment with fezolinetant, clinicians should obtain baseline serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and direct and total serum bilirubin levels to evaluate hepatic function and injury. ALT, AST, and bilirubin levels should also be obtained at 3 months, 6 months, and 9 months after treatment initiation and if symptoms suggesting liver injury occur, such as nausea, vomiting, or yellowing of the eyes or skin.

The dose of fezolinetant is 45 mg orally once daily with or without food. It should be taken with liquids and swallowed whole at about the same time each day. The tablet should not be chewed, crushed, or cut. Fezolinetant is supplied as a 45-mg tablet.¹

CLINICAL TRIALS

The efficacy of fezolinetant for the management of moderate to severe VMSs due to menopause was evaluated in two 12-week, double-blind, placebo-controlled, randomized trials (NCT04003155 and NCT04003142). The coprimary efficacy end points for both trials were the mean change from baseline in moderate to severe VMS frequency and severity at week 4 and week 12. Each trial found a statistically significant and clinically meaningful (≥2 hot flashes over 24 hours) reduction from baseline in the frequency and severity of moderate to severe VMSs for fezolinetant 45 mg compared with the placebo.¹

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with fezolinetant is contraindicated in patients with end-stage renal disease, severe renal impairment, and known cirrhosis and during concomitant use with CYP1A2 inhibitors.

Elevations in ALT and/or AST levels more than 3 times the upper limit of normal (ULN) occurred in some patients during clinical trials. These patients were generally asymptomatic, and levels returned to or came close to pretreatment levels upon discontinuation or interruption of treatment. No elevations in total bilirubin level (more than twice the ULN) occurred. Treatment should not be initiated if serum transaminase concentration is equal to or exceeds twice the ULN or if total bilirubin level is elevated. Followup evaluations of hepatic transaminase level should be obtained at 3 months, 6 months, and 9 months after beginning treatment.

Fezolinetant has not been evaluated in patients with cirrhosis. There are no data regarding the use of fezolinetant during pregnancy or on the presence of fezolinetant in human milk, the effects on the breastfed child, or the effects on milk production.

The most common adverse reactions with fezolinetant are abdominal pain, back pain, diarrhea, hepatic transaminase level elevation, hot flushes, and insomnia.¹

About the Author

Monica Holmberg, PharmD, BCPS, is a pharmacist in Phoenix, Arizona, and a Pharmacy Times contributor.

References

1. Veozah. Prescribing information. Astellas Pharma US Inc; 2023. Accessed May 31, 2023.https://www.astellas.com/us/system/files/veozah_uspi.pdf
2. Astellas’ VEOZAH (fezolinetant) approved by U.S. FDA for treatment of vasomotor symptoms due to menopause. News release. Astellas Pharma. May 12, 2023. Accessed May 31, 2023. https://newsroom.astellas.us/2023-05-12-Astellas-VEOZAH-TM-fezolinetant-Approved-by-U-S-FDA-for-Treatment-of-Vasomotor-Symptoms-Due-to-Menopause