Alprazolam and Buprenorphine and naloxone interaction

Alprazolam and Buprenorphine and naloxone: 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 Alprazolam (Alprazolam XR) label · effective 2025-02-11

Major

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

• Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

• Effects on Driving and Operating Machinery: Patients receiving • alprazolam XR should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs.

Warnings and precautionsby drug classView label on DailyMed
Major

Advise both patients and caregivers about the risks of respiratory depression and sedation when alprazolam XR is used with opioids.

Warnings and precautionsby drug classView label on DailyMed
Major

• Use with Opioids: Increase the risk of respiratory depression.

Drug interactionsby drug classView label on DailyMed

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

Major

Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol.

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

As a routine part of orientation to buprenorphine treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol.

Warnings and precautionsby drug classView label on DailyMed
Moderate

There is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients.

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.