Lynkuet · 4.8 Undesirable effects · 1

HOS-100780 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The most frequent adverse reactions (≥5%) with elinzanetant are: - for VMS associated with menopause: headache (7.8%) and fatigue (5.0%) - for VMS caused by AET: fatigue (14.2%), somnolence (9.5%), diarrhoea (7.1%), depression (6.2%), and muscle spasm (5.2%). Tabulated list of adverse reactions The safety profile of elinzanetant is based on data from women who received at least 1 dose of 120 mg elinzanetant: - 1 113 treated women with VMS associated with menopause in 3 phase III (OASIS 1, OASIS 2, OASIS 3) and 1 phase II (SWITCH-1) clinical studies and - 465 treated women with VMS caused by AET in a separate phase III clinical study (OASIS 4). The adverse reactions are listed in table 1. They are classified according to MedDRA System Organ Class. Adverse reactions are grouped according to their frequencies. Frequency groups are defined by the following convention: 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), not known (cannot be estimated from available data). 5 Table 1: Adverse reactions System organ class Frequency VMS associated with VMS caused by AET menopause Psychiatric disorders Common Depression Depressive mood Nervous system disorders Common Dizziness Dizziness Headache Somnolence Somnolence Vertigo Gastrointestinal disorders Common Abdominal pain Diarrhoea Diarrhoea Hepatobiliary disorders Common Alanine aminotransferase (ALT) increased* Uncommon Alanine Aspartate aminotransferase (ALT) aminotransferase (AST)

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100776 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Known or suspected pregnancy (see section 4.6).

HOS-100775 · has-indication-information · PDF-Seite 2

Lynkuet is indicated for the treatment of moderate to severe vasomotor symptoms (VMS): - associated with menopause (see section 5.1) - caused by adjuvant endocrine therapy (AET) related to breast cancer (see section 5.1).

HOS-100778 · has-interaction-information · PDF-Seite 4

Effects of other medicinal products on elinzanetant Elinzanetant is metabolised via CYP3A4 and is a substrate for the P-glycoprotein (P-gp) transporter protein. CYP3A4 inhibitors (substances increasing exposure to elinzanetant) Co-administration of multiple daily doses of itraconazole (200 mg), a strong CYP3A4 and P-gp inhibitor, and elinzanetant 120 mg resulted in an increase of approximately 3.3-fold in Cmax and between 4.6-fold and 6.3-fold in area under the curve (AUC) of elinzanetant. Physiologically based pharmacokinetic (PBPK) modelling predictions after co-administration of 120 mg elinzanetant with the moderate CYP3A4 inhibitor erythromycin showed a 3-fold increase of AUC and 2-fold increase for Cmax of elinzanetant. PBPK predictions after co-administration of 60 mg elinzanetant with the moderate CYP3A4 inhibitor erythromycin showed a 1.4-fold increase of AUC and no increase in Cmax compared to 120 mg elinzanetant alone. PBPK predictions after co-administration of 120 mg elinzanetant with the weak CYP3A4 inhibitor cimetidine showed a 1.5-fold increase of AUC and 1.3-fold increase for Cmax of elinzanetant. Elinzanetant should not be used together with strong CYP3A4 inhibitors (e.g. itraconazole, clarithromycin, ritonavir, cobicistat or ribociclib) (see section 4.4). The concomitant use of elinzanetant with grapefruit (juice) is not recommended. If used concomitantly with moderate CYP3A4 inhibitors (e.g. erythromycin, ciprofloxacin, fluconazole, verapamil) the daily dose of elinzanetant is 60 mg (see section 4.2). No dose adjustment is required for weak CYP3A4 inhibitors. Effects of elinzanetant on other medicinal products Elinzanetant is a weak inhibitor of CYP3A4. Co-administration of midazolam, a sensitive substrate of CYP3A4, and multiple daily doses of elinzanetant 120 mg resulted in an increase of 1.5-fold in Cmax and 1.8-fold in AUC of midazolam. Caution is required when co-administering elinzanetant with sensitive CYP3A4 substrates with a narrow therapeutic window (e.g. cyclosporine, fentanyl or tacrolimus). The related recommendation in the product information of these CYP3A4 substrates should be followed. 4

HOS-100779 · has-pregnancy-information · PDF-Seite 5

Pregnancy Lynkuet is contraindicated during pregnancy (see section 4.3). If pregnancy occurs during treatment with Lynkuet, the treatment should be withdrawn. There are no or limited data from the use of elinzanetant in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).Women of child-bearing potential have to use effective contraception during treatment. Non-hormonal contraceptives are recommended for this population. Breast-feeding It is unknown whether elinzanetant/metabolites are excreted in human milk. Available pharmacokinetic data in animals have shown excretion of elinzanetant/metabolites in milk (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Lynkuet therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility No human data on the effect of elinzanetant on fertility are available. In the fertility study in female rats, elinzanetant did not affect fertility (see section 5.3).

HOS-100777 · has-warning-information · PDF-Seite 3

Concomitant use with other medicinal products Cytochrome P450 isoform 3A4 (CYP3A4) inhibitors may decrease the clearance of elinzanetant, resulting in higher exposure. The concomitant use of elinzanetant with strong CYP3A4 inhibitors is not recommended. For concomitant use with moderate CYP3A4 inhibitors reduce the dose of elinzanetant (see section 4.5). Elinzanetant in combination with other breast cancer treatments The use of elinzanetant has been evaluated in combination with AET consisting of aromatase inhibitors or tamoxifen, with or without GnRH agonists. A decision to treat women with elinzanetant who receive medication other than those evaluated in the clinical studies should be based on an individual benefit-risk consideration. 3 Concomitant use of hormone replacement therapy (HRT) with oestrogens to treat VMS associated with menopause Concomitant use of elinzanetant and HRT with oestrogens has not been studied, and therefore concomitant use is not recommended. Local vaginal preparations can be used. Excipient with known effect Sorbitol The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use when administered concomitantly.