Hydrocodone and ibuprofen and Midazolam interaction

Hydrocodone and ibuprofen 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 Midazolam (Midazolam in Sodium Chloride) label · effective 2025-03-02

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 Resuscitation Only 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 Opioid Analgesics and Other Sedative Hypnotics Concomitant use of benzodiazepines, including Midazolam in 0.9% Sodium Chloride Injection, and opioids may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION, AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS See full prescribing information for complete boxed warning.

Boxed warningby drug classView label on DailyMed
Major

Concomitant use of benzodiazepines with opioid analgesics may result in profound sedation, respiratory depression, coma, and death.

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

From the Hydrocodone and ibuprofen (Hydrocodone Bitartrate and Ibuprofen) label · effective 2025-12-23

Major

…STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P4503A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE AND IBUPROFEN…

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of Hydrocodone Bitartrate and Ibuprofen Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings].

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydrocodone Bitartrate and Ibuprofen Tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general…

Warningsby drug classView label on DailyMed
Major

…consider recommending or prescribing an opioid overdose reversal agent (see WARNINGS, DOSAGE AND ADMINISTRATION, and OVERDOSAGE) Advise both patients and caregivers about the risks of respiratory depression and sedation when Hydrocodone Bitartrate and Ibuprofen Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).

Warningsby 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.