Buprenorphine and naloxone and Hydromorphone interaction

Buprenorphine and naloxone and Hydromorphone: 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

Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents (e.g., naloxone, nalmefene), depending on the patient’s clinical status [see Overdosage ( 10 )] .

Warnings and precautionsnames Buprenorphine and naloxoneView label on DailyMed
Major

Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)].

Warnings and precautionsnames Buprenorphine and naloxoneView label on DailyMed
Major

Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Hydromorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Drug interactionsnames Buprenorphine and naloxoneView label on DailyMed
Major

Do not confuse Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] with standard parenteral formulations of Hydromorphone Hydrochloride Injection or other opioids, as overdose and death could result [see Warnings and Precautions ( 5.1 )].

Boxed warningby drug classView label on DailyMed
Major

…Because the use of Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of…

Boxed warningby drug classView label on DailyMed

From the Buprenorphine and naloxone label · effective 2026-06-16

Moderate

Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets [see Warnings and Precautions (5.3) , Drug Interactions (7) ] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of buprenorphine 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…

Warnings and precautionsby drug classView label on DailyMed
Moderate

In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient's buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use.

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.