QUVIVIQ

/ CTS

The recommended dose for adults is one tablet of 50 mg once per night, taken orally in the evening within 30 minutes before going to bed. Based on clinical judgement, some patients may be treated with 25 mg once per night.
The treatment duration should be as short as possible. The appropriateness of continued treatment should be assessed within 3 months and periodically thereafter. Clinical data are available for up to 12 months of continuous treatment.
Treatment can be stopped without down-titration.
See prescribing information for full details.

Treatment of adult patients with insomnia characterised by symptoms present for at least 3 months and considerable impact on daytime functioning.

* Hypersensitivity to the active substance or to any of the excipients
* Narcolepsy
* Concomitant use with strong CYP3A4 inhibitors

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. Caution should be exercised when prescribing concomitantly with CNS-depressant medicinal products due to potentially additive effects, and a dose adjustment of either this medical product or the concomitant CNS depressants should be considered. Patients should be cautioned about drinking alcohol during treatment.
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.
Symptoms similar to mild cataplexy have been reported with dual orexin receptor antagonists.
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, this medical product should be administered with caution in patients exhibiting symptoms of depression.
See prescribing information for full details.

Common: Headache, Somnolence, Dizziness, Nausea, Fatigue.
See prescribing information for full details.

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 is 25 mg.
No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated.
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. No dose adjustment is required when is used concomitantly with treatments that reduce gastric acidity.
Effect of daridorexant on the pharmacokinetics of other medicinal products
Substrates of CYP3A4
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 daridorexant 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 did not induce CYP3A4, therefore contraceptives can be co-administered with daridorexant.
Substrates of CYP2C9
Substrates of P-gp transporters
In a clinical study conducted in healthy subjects receiving daridorexant 50 mg and dabigatran etexilate, a sensitive P-gp substrate, dabigatran AUC and Cmax increased by 42% and 29%, respectively, indicating a mild P-gp inhibition. Simultaneous administration of daridorexant with P-gp substrates with a narrow therapeutic index (e.g., digoxin) should be handled with caution.
Alcohol
In healthy subjects, concomitant intake with alcohol led to a prolonged absorption of daridorexant (tmax increased by 1.25 h). Daridorexant exposure (Cmax and AUC) and t½ were unchanged.
Pharmacodynamic interactions
Alcohol
Co-administration of 50 mg daridorexant with alcohol led to additive effects on psychomotor performance.
See prescribing information for full details.

Pregnancy: There are no data on the use of daridorexant in pregnant women. Consequently, daridorexant should be used during pregnancy only if the clinical condition of the pregnant woman requires treatment with daridorexant.
Lactation: 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 therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

In clinical pharmacology studies, healthy subjects were administered single doses of up to 200 mg daridorexant (4 times the recommended dose). At supra-therapeutic doses, adverse reactions of somnolence, muscular weakness, disturbance in attention, fatigue, headache, and constipation were observed.
There is no specific antidote to an overdose of daridorexant. In the event of an overdose, general symptomatic and supportive medical care should be provided and patients should be carefully monitored. Dialysis is unlikely to be effective as daridorexant is highly protein-bound.