Tizanidine and Buprenorphine: 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
Tizanidine
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.
Buprenorphine (a strong pain and addiction-treatment medicine) and tizanidine (a muscle relaxer) both calm down your body and your nervous system. When you take them together, those calming effects add up. That can make you very drowsy, slow your breathing, and make it harder to have a bowel movement or empty your bladder.
This is a serious combination, but it does not mean you can't use both. Many people do, safely, when their care team is watching closely. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor about the best doses and what warning signs to watch for.
Effect: Additive CNS and respiratory depression, plus additive anticholinergic/reduced-GI-motility effects (risk of severe constipation, paralytic ileus, urinary retention). Tizanidine, an alpha-2 agonist muscle relaxant with sedating properties, compounds buprenorphine's opioid-mediated CNS and respiratory depression.
- Direction: Additive PD interaction, not a metabolic/prodrug effect; effects intensify.
- Severity/evidence: Major; probable.
- Onset: Unspecified.
- Management: Monitor for excess sedation, respiratory depression, urinary retention, reduced gastric motility. Reduce muscle relaxant dose as needed; consider prescribing naloxone. Do not withhold MAT solely due to this interaction.
What happens
Enhanced neuromuscular blocking action, an increased risk of respiratory depression and CNS depression and an increased risk of paralytic ileus
Interaction Deep Dive
Using buprenorphine together with anticholinergic drugs that also act as skeletal muscle relaxants can heighten the neuromuscular blocking effect of the muscle relaxants and lead to a greater degree of respiratory depression; it may additionally result in urinary retention or severe constipation that progresses to paralytic ileus. If these agents are given together, watch patients for indications of urinary retention, decreased gastric motility, or respiratory depression that could exceed what would normally be anticipated. Lower the muscle relaxant dose when needed, and consider prescribing naloxone for the emergency management of opioid overdose1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) faced an elevated risk of death. Based on an analysis of aggregate national death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent use of a CNS depressant. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 2.
Why it happens (mechanism)
Additive CNS depression; additive effects on gastric motility
How to manage this interaction
Your care team can manage this combination safely with a few precautions:
- Keep taking both as prescribed unless your prescriber tells you otherwise, especially if buprenorphine is treating opioid use disorder.
- Your team may adjust and individualize the tizanidine dose and monitor you more closely for heavy drowsiness, slow or shallow breathing, trouble urinating, or constipation.
- Ask your prescriber whether having naloxone at home makes sense for you.
Call your pharmacist or doctor right away if you notice unusual sleepiness, breathing changes, belly pain, or bloating with no bowel movements.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) had 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 when no CNS depressant therapy was given, among MAT-prescribed patients (aged 18 to 50). The findings showed a higher 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 combined MAT and benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results also 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 authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 2.
b) A study drawing on aggregate nationwide death certificate data from 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone along with other CNS depressants were commonly cited as contributors to these deaths. Concurrent alprazolam use appeared in 18.1% of cases, followed by oxycodone (10.1%), cocaine (9.6%), heroin (9%), and diazepam (6.6%). The FDA documented 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 deaths involving methadone was 10 times that of deaths involving buprenorphine, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is unknown 2.
Common questions
Can I take Tizanidine and Buprenorphine together?
Combining buprenorphine and tizanidine adds up their sedating effects and can dangerously slow breathing and gut function, so use both only under close medical supervision. Do not stop either drug on your own; talk with your care team and ask about naloxone. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tizanidine and Buprenorphine 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 Tizanidine and Buprenorphine interaction managed?
Your care team can manage this combination safely with a few precautions: Keep taking both as prescribed unless your prescriber tells you otherwise, especially if buprenorphine is treating opioid use disorder. Your team may adjust and individualize the tizanidine dose and monitor you more closely for heavy drowsiness, slow or shallow breathing, trouble urinating, or constipation. Ask your prescrib… 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 Tizanidine or Buprenorphine 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: 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.
Keep reading about Buprenorphine
Keep reading about Tizanidine
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