Quviviq

HOS-099873 · has-adverse-reaction-information · PDF-Seite 7

Summary of safety profile The most frequently reported adverse reactions were headache and somnolence. 7 The majority of adverse reactions were mild to moderate in intensity. No evidence of a dose- relationship for the frequency or severity of adverse reactions was observed. The adverse reaction profile in elderly subjects was consistent with younger subjects. Tabulated list of adverse reactions Table 1 shows adverse reactions that occurred in Study 1 and Study 2 or in post-marketing experience. The frequency of adverse reactions is defined using 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 the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The safety of daridorexant was evaluated in three placebo-controlled Phase 3 clinical studies. A total of 1847 subjects (including approximately 40% elderly subjects [≥ 65 years old]) received daridorexant 50 mg (N = 308); 25 mg (N = 618); or 10 mg (N = 306), or placebo (N = 615). A total of 576 subjects were treated with daridorexant for at least 6 months and 331 for at least 12 months. Table 1: Adverse reactions System organ class Adverse reaction Frequency Immune system disorders Hypersensitivity (including Uncommon rash, urticaria) Psychiatric disorders Hallucination Uncommon Abnormal dreams, Uncommon nightmares Somnambulism Uncommon Nervous system disorders Headache Common Somnolence Common Dizziness Common Sleep paralysis Uncommon Gastrointestinal disorders Nausea Common General disorders and administration site conditions Fatigue

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HOS-099869 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Narcolepsy. • Concomitant use with strong CYP3A4 inhibitors (see section 4.5). 3

HOS-099868 · has-indication-information · PDF-Seite 2

QUVIVIQ is indicated for the treatment of adult patients with insomnia characterised by symptoms present for at least 3 months and considerable impact on daytime functioning.

HOS-099871 · has-interaction-information · PDF-Seite 5

Effect of other medicinal products on the pharmacokinetics of daridorexant CYP3A4 inhibitors In healthy subjects, co-administration of daridorexant 25 mg with the moderate CYP3A4 inhibitor diltiazem (240 mg once daily) increased daridorexant exposure parameters AUC and Cmax by 2.4 times and 1.4 times, respectively. In patients taking moderate CYP3A4 inhibitors (e.g., erythromycin, ciprofloxacin, cyclosporine), the recommended dose of QUVIVIQ is 25 mg. No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated (see section 4.3). The consumption of grapefruit or grapefruit juice in the evening should be avoided. CYP3A4 inducers In healthy subjects, co-administration with efavirenz (600 mg once daily), a moderate CYP3A4 inducer, decreased daridorexant exposure parameters AUC and Cmax by 61% and 35%, respectively. Based on these results, concomitant use with a moderate or strong CYP3A4 inducer substantially decreases exposure to daridorexant, which may reduce efficacy. Gastric pH-modifiers The solubility of daridorexant is pH-dependent. In healthy subjects, co-administration with famotidine (40 mg), an inhibitor of gastric acid secretion, decreased daridorexant Cmax by 39% while AUC remained unchanged. 5 No dose adjustment is required when QUVIVIQ is used concomitantly with treatments that reduce gastric acidity. Citalopram In healthy subjects, co-administration of 20 mg citalopram, a selective serotonin re-uptake inhibitor (SSRI), did not have any clinically relevant effect on the PK of 50 mg daridorexant. Effect of daridorexant on the pharmacokinetics of other medicinal products Substrates of CYP3A4 In a clinical study conducted in healthy subjects receiving daridorexant and midazolam, a sensitive CYP3A4 substrate, daridorexant at a dose of 25 mg did not affect the PK of midazolam, indicating an absence of CYP3A4 induction or inhibition at this dose. In a clinical study conducted in healthy subjects receiving 50 mg daridorexant and midazolam, exposure (AUC) to midazolam increased by 42%, indicating a mild CYP3A4 inhibition. Simultaneous administration of 50 mg QUVIVIQ with sensitive CYP3A4 substrates with a narrow therapeutic index (e.g., high-dose simvastatin, tacrolimus) should be handled with caution. In the same study, daridorexant 50 mg administered for 7 days d

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HOS-099872 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are no data on the use of daridorexant in pregnant women. Animal studies did not indicate harmful effects with respect to reproductive toxicity (see section 5.3). Consequently, QUVIVIQ should be used during pregnancy only if the clinical condition of the pregnant woman requires treatment with daridorexant. Breast-feeding Available data from a lactation study in 10 healthy lactating women receiving 50 mg daridorexant indicates that the presence of daridorexant in breast milk is low, with a fraction of the maternal dose of daridorexant excreted into breast milk of 0.02%. A risk of excessive somnolence to the breastfed infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from QUVIVIQ 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 concerning the effect of exposure to daridorexant on human fertility. Animal studies indicate no impact on male or female fertility (see section 5.3).

HOS-099870 · has-warning-information · PDF-Seite 4

Elderly Because of the general risk of falls in the elderly, daridorexant should be used with caution in this population, although clinical studies did not show an increase in the incidence of falls on daridorexant compared to placebo. QUVIVIQ should be administered with caution in patients older than 75 years since efficacy and safety data in this population are limited. CNS-depressant effects Because daridorexant acts by reducing wakefulness, patients should be cautioned about engaging in potentially hazardous activities, driving, or operating heavy machinery unless they feel fully alert, especially in the first few days of treatment (see section 4.7). Caution should be exercised when prescribing QUVIVIQ concomitantly with CNS-depressant medicinal products due to potentially additive effects, and a dose adjustment of either QUVIVIQ or the concomitant CNS depressants should be considered. Patients should be cautioned about drinking alcohol during treatment with QUVIVIQ (see section 4.5). Sleep paralysis, hallucinations, and cataplexy-like symptoms Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions, can occur with daridorexant, mainly during the first weeks of treatment (see section 4.8). Symptoms similar to mild cataplexy have been reported with dual orexin receptor antagonists. Prescribers should explain the nature of these events to patients when prescribing QUVIVIQ. Should such events occur, patients need to be further evaluated and, depending on the nature and severity of the events, discontinuation of treatment should be considered. Worsening of depression and suicidal ideation In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions have been reported. As with other hypnotics, QUVIVIQ should be administered with caution in patients exhibiting symptoms of depression. Isolated cases of suicidal ideation have been reported in Phase 3 clinical studies, in subjects with pre- existing psychiatric conditions and/or stressful living conditions, across all treatment groups, including placebo. Suicidal tendencies may be present in patients with depression and protective measures may be required. Patients with psychiatric co-morbidities QUVIVIQ should be administered with caution in patients with psychiatric co-morbidities since efficacy and safety data

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