VEOZAH

VEOZAH- fezolinetant tablet, film coated
Astellas Pharma US, Inc.

1 INDICATIONS AND USAGE

VEOZAH^™ is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Perform baseline bloodwork to evaluate for hepatic function and injury [including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and serum bilirubin (total and direct)] before initiating treatment with VEOZAH. While using VEOZAH, perform follow-up bloodwork 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 [see Warnings and Precautions (5.1)].

Take a single 45 mg VEOZAH tablet orally once daily with or without food.

Take VEOZAH with liquids and swallow whole. Do not cut, crush, or chew tablets.

Administer VEOZAH orally at about the same time each day. 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. Return to the regular schedule the following day.

3 DOSAGE FORMS AND STRENGTHS

Tablets: 45 mg, round, light red, film-coated tablets, debossed with the Astellas logo and ‘645’ on the same side.

4 CONTRAINDICATIONS

VEOZAH is contraindicated in women with any of the following conditions:

•

Known cirrhosis [see Warnings and Precautions (5.1), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

•

Severe renal impairment or end-stage renal disease [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

•

Concomitant use with CYP1A2 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Hepatic Transaminase Elevation

Elevations in serum transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels greater than three times the upper limit of normal (ULN) occurred 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) of women receiving placebo in three clinical trials. No serum elevations in total bilirubin (greater than two times the ULN) occurred. Women with ALT or AST elevations were generally asymptomatic. Transaminase levels returned to pretreatment levels (or close to these) without sequelae with dose continuation, and upon dose interruption, or discontinuation. Women with cirrhosis were not studied [see Adverse Reactions (6.1)].

Perform baseline bloodwork to evaluate for hepatic function and injury [including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and serum bilirubin (total and direct)] prior to VEOZAH initiation. Do not start VEOZAH if concentration of ALT or AST is equal to or exceeds two times the ULN or if the total bilirubin is elevated (for example, equal to or exceeds two times the ULN) for the evaluating laboratory. If baseline hepatic transaminase evaluation is less than two times the ULN and the total bilirubin is normal, VEOZAH can be started. Perform follow-up evaluations of hepatic transaminase concentration 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.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of VEOZAH was evaluated in three 52-week clinical trials [see Clinical Studies (14)]. Across the three clinical trials, a total of 1100 women received VEOZAH. Trials 1 and 2 were placebo-controlled for the first 12 weeks, followed by re-randomization of women previously receiving placebo to VEOZAH (women on VEOZAH remained on VEOZAH) for an additional 40 weeks of uncontrolled treatment. Trial 3 was a randomized, placebo-controlled, double-blind safety study evaluating the safety of VEOZAH for 52 weeks. The adverse reactions reported in at least 2% in VEOZAH 45 mg and greater than placebo in Trial 3 are presented in Table 1.

Table 1: Adverse Reactions Reported in at Least 2% in VEOZAH 45 mg and Greater Than Placebo in a Placebo-Controlled, Double-Blind 52-Week Trial (Trial 3)

* EAIR = Number of individuals experiencing an adverse event divided by exposure time (total person-years) x 100. † Abdominal pain (including Abdominal pain, Abdominal pain lower, Abdominal pain upper). ‡ Hepatic transaminase elevations (including Alanine aminotransferase abnormal, Alanine aminotransferase increased, Aspartate aminotransferase abnormal, Aspartate aminotransferase increased).
Adverse Reaction	VEOZAH 45 mg (n=609) Total Person-Years=504.2 n (%, EAIR * )	Placebo (n=610) Total Person-Years=475.0 n (%, EAIR * )
Abdominal pain †	26 (4.3%, 5.2)	13 (2.1%, 2.7)
Diarrhea	24 (3.9%, 4.8)	16 (2.6%, 3.4)
Insomnia	24 (3.9%, 4.8)	11 (1.8%, 2.3)
Back pain	18 (3.0%, 3.6)	13 (2.1%, 2.7)
Hot flush	15 (2.5%, 3.0)	10 (1.6%, 2.1)
Hepatic transaminase elevation ‡	14 (2.3%, 2.8)	5 (0.8%, 1.1)

In the pooled laboratory data of Trials 1, 2, and 3, elevated hepatic transaminases (greater than 3 times the ULN) occurred in 25 women (2.3%, 2.7 EAIR) exposed to VEOZAH 45 mg (n=1100, 912.1 total person-years) as compared to 8 women (0.9%, 1.5 EAIR) exposed to placebo (n=952, 549.1 total person-years).