Daridorexant and Nirmatrelvir and ritonavir interaction

Daridorexant and Nirmatrelvir and ritonavir: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Daridorexant (QUVIVIQ) label · effective 2026-02-26

Major

Strong CYP3A4 inhibitors: Avoid concomitant use.

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Major

Concomitant use of QUVIVIQ with a strong inhibitor of CYP3A4 is not recommended [see Dosage and Administration (2.2) ] .

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Moderate

Moderate CYP3A4 inhibitors: Maximum recommended dose is 25 mg.

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Moderate

Table 2 Effects of Other Drugs on QUVIVIQ Strong or Moderate CYP3A4 Inhibitors Clinical Implications: Concomitant use with a strong or moderate CYP3A4 inhibitor increases exposure to daridorexant [see Clinical Pharmacology (12.3) ] , which may increase the risk of QUVIVIQ adverse reactions.

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Moderate

Prevention or Management: The recommended dose of QUVIVIQ is 25 mg when used with a moderate CYP3A4 inhibitor [see Dosage and Administration (2.2) ] .

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From the Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19

Major

…(selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial hypertension (PAH) • Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin • Vasopressin receptor antagonists: tolvaptan ➢ Drugs that…

Contraindicationsby drug classView label on DailyMed
Major

Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] .

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Major

Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist flibanserin ↑ flibanserin Co-administration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4) ] .

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Moderate

Sedative/hypnotics buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem ↑ sedative/hypnotic A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events. midazolam (administered parenterally) ↑ midazolam Co-administration of midazolam (parenteral) should be done in a setting which ensures close…

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.