Buprenorphine and Hydroxyzine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Hydroxyzine
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Taking buprenorphine (an opioid used for pain or for opioid use disorder) together with hydroxyzine (used for anxiety, itching, or sleep) can add their effects together. Both can slow your breathing and make you very sleepy, and both can affect your heart's rhythm (something called QT prolongation). The combination can also slow your gut, causing bad constipation or trouble passing urine.
This is a serious combination, but it can be managed. Do not stop either medicine on your own. Talk with your doctor or pharmacist. They may adjust doses, watch you more closely, or suggest a different option for anxiety or sleep, and they may recommend keeping naloxone on hand just in case.
Additive pharmacodynamic interaction. Buprenorphine (opioid partial agonist) and hydroxyzine (sedating antihistamine) combine to produce:
- Additive QT prolongation (both agents prolong QTc)
- Additive CNS and respiratory depression (sedation, coma, death)
- Additive anticholinergic/GI effects (constipation, paralytic ileus, urinary retention)
Severity: major. Evidence: probable. Onset: unspecified. No prodrug considerations; this is a PD, not PK, interaction. Management: avoid where possible; cessation of the CNS depressant is preferred. If continued, use lowest effective dose, monitor for sedation, respiratory depression, urinary retention, and severe constipation, obtain ECG if additional QT risk factors, consider alternative anxiolytics, and strongly consider co-prescribing naloxone. Do not withhold MAT.
What happens
An increased risk of QT interval prolongation, an increased risk of CNS and respiratory depression and an increased risk of paralytic ileus
Interaction Deep Dive
Steer clear of using buprenorphine together with agents that can lengthen the QT interval. Combining these drugs also heightens the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than administering them alongside buprenorphine. For certain patients, it may be suitable to provide monitoring at a higher level of care or to implement a taper. For others, it may be appropriate to slowly wean the patient off a prescribed CNS depressant or to reduce the amount to the lowest effective dose. When combined use cannot be avoided, watch for urinary retention, severe constipation, sedation, and respiratory depression; think about alternative therapies for managing anxiety or insomnia and give strong consideration to prescribing naloxone for emergency treatment of opioid overdose1. A Swedish epidemiological study found that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) in combination with benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a greater risk of death. Based on an analysis of aggregate nationwide death certificate records spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death associated with concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown 2.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression; additive effects on gastric motility
How to manage this interaction
This is a significant combination, but your care team can manage it safely.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Never stop buprenorphine on your own.
- Your team may lower the dose to the lowest effective amount, monitor you more closely, or choose a different option for anxiety or sleep.
- Ask whether you should have naloxone at home for emergencies.
- Report right away: heavy drowsiness, slow or shallow breathing, confusion, fainting or palpitations, severe constipation, or trouble urinating.
If you are on medication-assisted treatment, do not let this interaction scare you off it. Talk with your pharmacist or prescriber about the safest plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy in MAT prescribed patients (aged 18 to 50). The findings showed a raised risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with MAT combined with benzodiazepine treatment; however, these data were not deemed statistically significant. While the results indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent MAT and non-benzodiazepine use, only the data for fatal overdose and all-cause mortality were regarded as statistically significant; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication of use for the drugs 2.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often reported as culprits in those deaths. Concurrent alprazolam use was reported in 18.1% of cases, followed by oxycodone (10.1%), cocaine (9.6%), heroin (9%), and diazepam (6.6%). The FDA reported 322 drug overdose deaths in 2014 involving buprenorphine. Of these 322 deaths, 32.9% involved alprazolam, 17.4% involved clonazepam, 11.2% involved diazepam, 11.2% involved heroin, and 9.9% involved fentanyl. The absolute number of methadone-involved deaths was 10 times the number of buprenorphine-involved deaths, although confounding factors and differences in drug utilization were not taken into account. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 2.
Common questions
Can I take Buprenorphine and Hydroxyzine together?
Combining buprenorphine and hydroxyzine adds up their sedating, breathing-slowing, heart-rhythm, and gut-slowing effects, so avoid it when possible and only combine under close medical supervision. Do not change either medicine on your own; talk to your prescriber or pharmacist and ask about keeping naloxone available. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Hydroxyzine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Hydroxyzine interaction managed?
This is a significant combination, but your care team can manage it safely. Keep taking both as prescribed unless your prescriber tells you otherwise. Never stop buprenorphine on your own. Your team may lower the dose to the lowest effective amount, monitor you more closely, or choose a different option for anxiety or sleep. Ask whether you should have naloxone at home for emergencies. Report righ… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buprenorphine or Hydroxyzine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
Keep reading about Buprenorphine
Keep reading about Hydroxyzine
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