Hepatotoxicity

In three clinical trials, elevations in serum transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels > 3 x 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 fezolinetant (VEOZAH) and 0.9% (EAIR of 1.5 per 100 person-years) of women receiving placebo. No elevations in serum total bilirubin (> 2 x 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)].

In the postmarketing setting, cases of drug-induced liver injury with elevations of ALT, AST, alkaline phosphatase (ALP), and total bilirubin occurred within 40 days of starting fezolinetant (VEOZAH). Patients reported a general sense of feeling unwell and symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine. The patients’ signs and symptoms gradually resolved after discontinuation of fezolinetant (VEOZAH) [see Adverse Reactions (6.2)].

Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury [including serum ALT, serum AST, serum ALP, and serum bilirubin (total and direct)] prior to fezolinetant (VEOZAH) initiation. Do not start fezolinetant (VEOZAH) if ALT or AST is ≥ 2 x ULN or if the total bilirubin is ≥ 2 x ULN for the evaluating laboratory.

Perform follow-up hepatic laboratory tests monthly for the first 3 months, at 6 months, and 9 months after initiation of therapy.

Advise patients to discontinue fezolinetant (VEOZAH) immediately and seek medical attention including hepatic laboratory tests if they experience signs or symptoms that may suggest liver injury:

• new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain.

Discontinue fezolinetant (VEOZAH) if:

• transaminase elevations are > 5 x ULN.
• transaminase elevations are > 3 x ULN and total bilirubin is > 2 x ULN.

If transaminase elevations > 3 x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution.

Exclude alternative causes of hepatic laboratory test elevations