Nalbuphine and Nalmefene interaction

Nalbuphine and Nalmefene: 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 Nalbuphine (Nalbuphine Hydrochloride) label · effective 2026-07-16

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 ].

Warningsnames NalmefeneView label on DailyMed
Minor

Naloxone may reverse these effects.

Warningsby drug classView label on DailyMed
Minor

Maternal administration of naloxone during labor has normalized these effects in some cases.

Warningsby drug classView label on DailyMed
Minor

Drug Interactions Benzodiazepines and other Central Nervous System (CNS) Depressants Although Nalbuphine Hydrochloride Injection possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection of Nalbuphine Hydrochloride Injection.

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From the Nalmefene (Zurnai) label · effective 2026-07-31

Major

Risk of Recurrent Respiratory and CNS Depression : A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI using a new auto-injector with each dose while awaiting emergency medical assistance.

Warnings and precautionsby drug classView label on DailyMed
Major

In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated.

Warnings and precautionsby drug classView label on DailyMed
Major

While the duration of action of nalmefene is as long as most opioids, a recurrence of respiratory depression is possible, even after an apparently adequate initial response to ZURNAI treatment [see Clinical Pharmacology (12.3) ].

Warnings and precautionsby drug classView label on DailyMed
Major

In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes.

Warnings and precautionsby drug classView label on DailyMed
Major

There may be clinical settings, particularly the postpartum period in neonates with known or suspected exposure to maternal opioid use, where it is preferable to avoid the abrupt precipitation of opioid withdrawal symptoms.

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.