Buprenorphine and naloxone and Sodium oxybate interaction

Buprenorphine and naloxone and Sodium oxybate: 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 Sodium oxybate (Xyrem) label · effective 2025-07-01

Major

• Central Nervous System Depression Xyrem (sodium oxybate) is a CNS depressant.

Boxed warningby drug classView label on DailyMed
Major

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Central Nervous System Depression • Xyrem is a CNS depressant, and respiratory depression can occur with Xyrem use ( 5.1 , 5.4 )

Boxed warningby drug classView label on DailyMed
Major

Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.

Warnings and precautionsby drug classView label on DailyMed
Major

Alcohol, Sedative Hypnotics, and CNS Depressants Xyrem is contraindicated for use in combination with alcohol or sedative hypnotics.

Drug interactionsby drug classView label on DailyMed

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

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
Moderate

Clinically Significant Drug Interactions with Buprenorphine and Naloxone Sublingual Tablets Benzodiazepines or other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound…

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.