Buprenorphine and Thioridazine: 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
Thioridazine
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 (like Belbuca, BuTrans, or Sublocade) together with thioridazine can pull in two directions, and both matter. First, thioridazine can speed up how your body breaks down buprenorphine, so you may get less pain or withdrawal relief and could feel opioid withdrawal symptoms coming on. Second, both drugs can add up to slow your breathing, make you very sleepy, affect your heart's rhythm, and cause severe constipation.
The good news is your care team can manage this. They may adjust your buprenorphine dose and watch you more closely. Please don't stop or change either medicine on your own. Just keep an open line with your pharmacist or doctor.
Direction: Thioridazine induces CYP3A4-mediated metabolism of buprenorphine, lowering buprenorphine exposure and risking withdrawal/reduced efficacy. Simultaneously, the pair produces additive PD effects: QT prolongation, CNS/respiratory depression, and reduced gastric motility (ileus).
- Severity/evidence: Major; probable substantiation.
- Management: Titrate buprenorphine to stable effect; monitor for withdrawal. On thioridazine discontinuation, consider buprenorphine dose reduction and monitor for respiratory depression.
- Monitor: Sedation, respiratory depression, ECG/QTc, urinary retention, constipation.
Prefer alternatives for anxiety/insomnia if possible. Do not withhold MAT solely due to this interaction; individualize and consider higher level of care where warranted.
What happens
Reduced buprenorphine exposure, reduced efficacy of buprenorphine, 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
Taking buprenorphine together with thioridazine can reduce buprenorphine exposure, produce opioid withdrawal symptoms, and may lengthen the QT interval. During coadministration, titrate the buprenorphine dose upward until stable drug effects are reached, while watching for withdrawal. If thioridazine is stopped in a patient who is on buprenorphine, a reduction in the buprenorphine dose should be considered, along with monitoring for respiratory depression. Combined use additionally raises the likelihood of respiratory depression, profound sedation, coma, and death. Discontinuing CNS depressants is preferable to using them concurrently. When concurrent use cannot be avoided, monitor for urinary retention, severe constipation, sedation, QT prolongation, and respiratory depression3. Patients on CNS depressant therapy should not be refused access to medication-assisted treatment (MAT) agents (for example, methadone and buprenorphine). Even though concomitant use heightens the risk of serious adverse effects, overdose, and death, denying MAT access may result in a greater risk of morbidity and mortality associated with opioid use disorder2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine; additive QT interval prolongation; additive CNS depression; additive effects on gastric motility
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Because these two can interact in more than one way, your care team will tailor your plan.
- Your buprenorphine dose may need to be adjusted and individualized until your symptoms are stable.
- Your team may monitor you more closely for withdrawal, heavy sedation, slowed breathing, heart rhythm (ECG), severe constipation, and trouble urinating.
- If thioridazine is later stopped, your buprenorphine dose may be lowered.
- Ask whether a different medicine for anxiety or sleep might be an option.
Report new drowsiness, breathing trouble, or withdrawal symptoms to your pharmacist or doctor promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed with periods without CNS depressant therapy among 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 and benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results showed an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent MAT and non-benzodiazepine use, only the fatal overdose and all-cause mortality data reached statistical significance; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. The benzodiazepine cohort and non-benzodiazepine cohort were not compared because the authors did not adjust for the indication of use for the drugs 2.
b) According to a study of pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly cited as contributors to those deaths. Concurrent ALPRAZolam use was noted 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 that involved buprenorphine. Among 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, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone remains unknown 2.
c) The impact of coadministered CYP3A4 inducers on buprenorphine exposure in individuals treated with subQ buprenorphine has not been studied; however, such interactions have been established in studies using transmucosal buprenorphine. Buprenorphine's effects may depend on the route of administration 1.
Common questions
Can I take Buprenorphine and Thioridazine together?
Thioridazine can lower buprenorphine levels (risking withdrawal) while also adding to sedation, slowed breathing, QT prolongation, and constipation, so your care team will adjust the dose and monitor you closely. Keep taking both as prescribed and report any withdrawal, extreme drowsiness, or breathing changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Thioridazine 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 Thioridazine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Because these two can interact in more than one way, your care team will tailor your plan. Your buprenorphine dose may need to be adjusted and individualized until your symptoms are stable. Your team may monitor you more closely for withdrawal, heavy sedation, slowed breathing, heart rhythm (ECG), severe constipatio… 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.
Questions for your pharmacist
- Does my dose of Buprenorphine or Thioridazine 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 (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. 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.
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Thioridazine
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