Hydromorphone and Phenobarbital interaction

Hydromorphone and Phenobarbital: 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 Hydromorphone (Hydromorphone Hydrochloride) label · effective 2026-07-15

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 Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7 )] .

Boxed warningby drug classView label on DailyMed
Major

• 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

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7 )] .

Warnings and precautionsby drug classView label on DailyMed

From the Phenobarbital (SEZABY) label · effective 2025-12-23

Major

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; DEPENDENCE AND WITHDRAWAL REACTIONS AFTER USE OF SEZABY FOR A LONGER DURATION THAN RECOMMENDED; and ABUSE, MISUSE AND ADDICTION WITH UNAPPROVED USE IN ADOLESCENTS AND ADULTS Risks from Concomitant Use with Opioids Concomitant use of phenobarbital products, including SEZABY, and opioids may result in profound sedation,…

Boxed warningby drug classView label on DailyMed
Major

Concomitant use of phenobarbital products, including SEZABY, and opioids may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

CNS depressants: Closely monitor for sedation and respiratory depression.

Drug interactionsby drug classView label on DailyMed
Major

CNS Depressants Closely monitor for signs of sedation and respiratory depression with concomitant use of SEZABY with other CNS depressants, including opioids [see Warnings and Precautions (5.1)] .

Drug interactionsby drug classView label on DailyMed
Moderate

Risks from Concomitant Use with Opioids Concomitant use of phenobarbital products, including SEZABY, and opioids may result in profound sedation, respiratory depression, coma, and death [see Drug Interactions (7.3)] .

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.