Lemborexant and Methadone interaction

Lemborexant and Methadone: 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 Methadone (METHADOSE) label · effective 2026-04-27

Major

Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate.

Boxed warningby drug classView label on DailyMed
Major

Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, and death.

Boxed warningby drug classView label on DailyMed
Moderate

…Concomitant Use of Benzodiazepines or Other CNS Depressants with Methadone Concomitant use of methadone and benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), increases the risk…

Warnings and precautionsby drug classView label on DailyMed
Moderate

As a routine part of orientation to methadone treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, or alcohol.

Warnings and precautionsby drug classView label on DailyMed

From the Lemborexant (DAYVIGO) label · effective 2025-02-24

Moderate

CNS Depressant Effects and Daytime Impairment: Impairs alertness and motor coordination including morning impairment.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risk increases with dose and use with other central nervous system (CNS) depressants.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Dosage adjustments of DAYVIGO and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects.

Warnings and precautionsby drug classView label on DailyMed
Minor

Examples: Bupropion, methadone

Drug interactionsnames MethadoneView label on DailyMed

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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.