Buprenorphine and naloxone and Promethazine and dextromethorphan interaction
Buprenorphine and naloxone and Promethazine and dextromethorphan: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Buprenorphine and naloxone label · effective 2026-06-16
Serotonergic Drugs: Concomitant use may result in serotonin syndrome.
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) ] .
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…
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.
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.
From the Promethazine and dextromethorphan (Promethazine Hydrochloride and Dextromethorphan Hydrobromide) label · effective 2025-08-08
The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine…
It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.
CNS Depressants – Promethazine may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced…
When given concomitantly with Promethazine Hydrochloride and Dextromethorphan Hydrobromide Oral Solution, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half.
Excessive amounts of promethazine relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.
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Open in the checkerNot 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.