Doxepin and Nalbuphine interaction

Doxepin and Nalbuphine: 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

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 Nalbuphine Hydrochloride Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see WARNINGS , PRECAUTIONS; Drug Interactions ].

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 Nalbuphine Hydrochloride Injection with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants,…

Warningsby drug classView label on DailyMed
Major

Advise both patients and caregivers about the risks of respiratory depression and sedation when Nalbuphine Hydrochloride Injection is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).

Warningsby drug classView label on DailyMed
Major

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see PRECAUTIONS; Drug Interactions and Information for Patients ].

Warningsby drug classView label on DailyMed

From the Doxepin (Silenor) label · effective 2026-04-21

Moderate

Potential additive effects when used in combination with CNS depressants or sedating antihistamines.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When taken with SILENOR, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [s ee Warnings and Precautions (5.2) and Drug Interactions (7.3 , 7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Patients should be cautioned about potential additive effects of SILENOR used in combination with CNS depressants or sedating antihistamines [s ee Warnings and Precautions (5.2) and Drug Interactions (7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

CNS Depressants and Sedating Antihistamines: Sedative effects may be increased with doxepin.

Drug interactionsby 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.