Eszopiclone and Midazolam interaction

Eszopiclone and Midazolam: 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 Eszopiclone (Lunesta) label · effective 2025-01-08

Major

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended.

Warnings and precautionsby drug classView label on DailyMed
Moderate

CNS Depressant Effects: Impaired alertness and motor coordination, including risk of morning impairment.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risk increases with dose and use with other CNS depressants and alcohol.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Post-marketing reports have shown that complex sleep behaviors may occur with LUNESTA alone at recommended dosages, with or without the concomitant use of alcohol or other CNS depressants [see Drug Interactions ( 7.1 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

CNS Depressant Effects and Next-Day Impairment LUNESTA is a CNS depressant and can impair daytime function in some patients at the higher doses (2 mg or 3 mg), even when used as prescribed.

Warnings and precautionsby drug classView label on DailyMed

From the Midazolam (Midazolam in Sodium Chloride) label · effective 2025-07-31

Major

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION, AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS Personnel and Equipment for Monitoring and ResuscitationOnly personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer…

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Opioids, Other Sedative Hypnotics, or Other Central Nervous System Depressants Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Warnings and precautionsby drug classView label on DailyMed
Major

Opioid Analgesics and Other Sedative Hypnotics : Risk of respiratory depression is increased ( 7.1 )

Drug interactionsby drug classView label on DailyMed
Major

Opioid Analgesics and Other Sedative Hypnotics The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.

Drug interactionsby drug classView label on DailyMed
Moderate

Because intravenous midazolam can depress respiration [see Clinical Pharmacology (12)] , especially when used concomitantly with opioid agonists and other sedatives [see Dosage and Administration (2)] , it should be used for sedation/anxiolysis/amnesia only in the presence of personnel skilled in early detection of hypoventilation, maintaining a patent airway,…

Warnings and precautionsby drug classView 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.