Fezolinetant

Fezolinetant is not recommended for use in individuals with severe (eGFR less than 30 ml/min/1.73 m²) renal impairment. Fezolinetant has not been studied in individuals with end-stage renal disease (eGFR less than 15 ml/min/1.73 m²) and is not recommended for use in this population.

Fezolinetant is not recommended for use in individuals with Child-Pugh Class B (moderate) or C (severe) chronic hepatic impairment. Fezolinetant has not been studied in individuals with Child-Pugh Class C (severe) chronic hepatic impairment.

Women with active liver disease or Child-Pugh Class B (moderate) or C (severe) chronic hepatic impairment have not been included in the clinical efficacy and safety studies with fezolinetant and this information cannot be reliably extrapolated. The pharmacokinetics of fezolinetant has been studied in women with Child-Pugh Class A (mild) and B (moderate) chronic hepatic impairment. Monitoring of liver function in women with known or suspected hepatic disorder is advised during treatment.

Concomitant use of fezolinetant and hormone replacement therapy with oestrogens has not been studied, and therefore concomitant use is not recommended.

Local vaginal preparations excluded.

Women undergoing oncologic treatment (e.g., chemotherapy, radiation therapy, anti-hormone therapy) for breast cancer or other oestrogen-dependent malignancies have not been included in the clinical studies. Therefore, fezolinetant is not recommended for use in this population as the safety and efficacy are unknown.

Women with previous breast cancer or other oestrogen-dependent malignancies and no longer on any oncologic treatment have not been included in the clinical studies. A decision to treat these women with fezolinetant should be based on a benefit-risk consideration for the individual.

Fezolinetant has not been studied in women with a history of seizures or other convulsive disorders. There were no cases of seizures or convulsive disorders during clinical studies. A decision to treat these women with Veoza should be based on a benefit-risk consideration for the individual.

Fezolinetant is contraindicated during pregnancy. If pregnancy occurs during use with fezolinetant, treatment should be withdrawn immediately.

There are no or limited data from the use of fezolinetant in pregnant women. Studies in animals have shown reproductive toxicity. Perimenopausal women of childbearing potential should use effective contraception. Non-hormonal contraceptives are recommended for this population.

Fezolinetant is not indicated during lactation.

It is unknown whether fezolinetant and its metabolites are excreted in human milk. Available pharmacokinetic data in animals showed excretion of fezolinetant and/or its metabolites in animal milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from fezolinetant therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effect of fezolinetant on human fertility. In the fertility study in female rats, fezolinetant did not affect fertility.

Fezolinetant has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequent adverse reactions with fezolinetant 45 mg were diarrhoea (3.2%) and insomnia (3.0%).

There were no serious adverse reactions reported at an incidence greater than 1% across the total study population. On fezolinetant 45 mg, four serious adverse reactions were reported. The most serious adverse reaction was an event of endometrial adenocarcinoma (0.1%).

The most frequent adverse reactions leading to dose discontinuation with fezolinetant 45 mg were alanine aminotransferase (ALT) increased (0.3%) and insomnia (0.2%).

Tabulated list of adverse reactions

The safety of fezolinetant has been studied in 2203 women with VMS associated with menopause receiving fezolinetant once daily in phase 3 clinical studies.

Adverse reactions observed during clinical studies are listed below by frequency category in each system organ class. Frequency categories are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); and not known (cannot be estimated from the available data).

Table 1. Adverse reactions for fezolinetant 45 mg: