Midazolam and Sodium oxybate interaction

Midazolam and Sodium oxybate: 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 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

From the Sodium oxybate (Xyrem) label · effective 2025-07-01

Major

• Central Nervous System Depression Xyrem (sodium oxybate) is a CNS depressant.

Boxed warningby drug classView label on DailyMed
Major

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Central Nervous System Depression • Xyrem is a CNS depressant, and respiratory depression can occur with Xyrem use ( 5.1 , 5.4 )

Boxed warningby drug classView label on DailyMed
Major

Xyrem is contraindicated for use in: • combination with sedative hypnotics [see Warnings and Precautions ( 5.1 )] .

Contraindicationsby drug classView label on DailyMed
Major

• In combination with sedative hypnotics or alcohol ( 4 )

Contraindicationsby 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.