Quviviq Drug Interactions

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 C_max 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 Contraindications).
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 C_max 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 C_max by 39% while AUC remained unchanged.
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 did not induce CYP3A4, therefore contraceptives can be co-administered with QUVIVIQ.
Substrates of CYP2C9: In a clinical study conducted in healthy subjects receiving daridorexant and warfarin, a sensitive CYP2C9 substrate, daridorexant at a dose of 50 mg did not affect the PK and PD of warfarin, indicating an absence of effect on CYP2C9. CYP2C9 substrates can be administered with QUVIVIQ without dose adjustment.
Substrates of BCRP or P-gp transporters: In clinical studies conducted in healthy subjects receiving 25 mg and 50 mg daridorexant and rosuvastatin, a BCRP substrate, daridorexant did not affect the PK of rosuvastatin, indicating an absence of inhibition of BCRP. BCRP substrates can be administered with QUVIVIQ without dose adjustment.
In a clinical study conducted in healthy subjects receiving daridorexant 50 mg and dabigatran etexilate, a sensitive P-gp substrate, dabigatran AUC and C_max increased by 42% and 29%, respectively, indicating a mild P-gp inhibition. Simultaneous administration of QUVIVIQ 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 (t_max increased by 1.25 h). Daridorexant exposure (C_max and AUC) and t¹/₂ were unchanged.
Citalopram: In healthy subjects, the PK of citalopram at steady state was not affected by co-administration of 50 mg daridorexant.
Pharmacodynamic interactions: Alcohol: Co-administration of 50 mg daridorexant with alcohol led to additive effects on psychomotor performance.
Citalopram: No relevant interaction on psychomotor performance was observed when 50 mg daridorexant was co-administered with 20 mg citalopram in healthy subjects at steady state.
Paediatric population: Interaction studies have only been performed in adults.