Can phenobarbital be taken concurrently with Subutex (buprenorphine)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 25, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Concurrent Use of Phenobarbital and Subutex (Buprenorphine)

Yes, phenobarbital and Subutex can be taken together, and this combination has been used successfully in clinical practice for managing withdrawal syndromes in patients on buprenorphine therapy. 1, 2

Evidence Supporting Concurrent Use

The combination of phenobarbital with buprenorphine has documented clinical applications:

  • A case report demonstrated successful emergency management of a patient with high-dose tramadol withdrawal who was treated with both buprenorphine and phenobarbital concurrently, then linked to ongoing outpatient treatment. 1

  • Another case documented a patient on buprenorphine maintenance who developed physiologic dependence to phenibut (a GABA-B agonist) and was successfully treated with a phenobarbital taper while continuing buprenorphine therapy. 2

  • Phenobarbital is recommended in epilepsy guidelines as an appropriate antiepileptic medication that can be used in various clinical contexts, including when patients may be on other medications. 3

Important Safety Considerations

While the combination can be used, you must monitor for additive central nervous system depression:

  • Both medications are CNS depressants and can cause respiratory depression, profound sedation, and potentially death when combined with other sedating agents. 3

  • Close monitoring for progressive sedation is essential, as sedation often precedes respiratory depression. Check respiratory rate, oxygen saturation, and level of consciousness frequently after initiating or adjusting either medication. 4

  • Naloxone should be available for emergency reversal of opioid-induced respiratory depression in this setting. 4

Clinical Management Algorithm

When prescribing these medications together:

  • Limit dosages to the minimum effective amounts and use the shortest duration necessary for the clinical indication. 4

  • Schedule regular follow-up visits to evaluate for signs of respiratory compromise or excessive sedation. 4

  • Educate patients and caregivers about warning signs of respiratory depression (extreme drowsiness, difficulty staying awake, slow or shallow breathing). 4

  • Avoid adding additional CNS depressants (benzodiazepines, alcohol, other sedatives) as this significantly increases overdose risk. 4

Common Pitfalls to Avoid

  • Do not assume the partial agonist properties of buprenorphine eliminate respiratory depression risk when combined with barbiturates—the combination still carries significant CNS depression potential. 3, 4

  • Do not prescribe without establishing a monitoring plan—these patients require closer follow-up than those on either medication alone. 4

  • Do not overlook the indication for phenobarbital—if it's being used for seizure control, abrupt discontinuation poses seizure risk, so the combination may be medically necessary despite the interaction. 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Safety Recommendations for Concurrent Use of Buprenorphine and Benzodiazepines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Related Questions

Should a patient with a history of fentanyl use, who hasn't used opioids in 3 days and is experiencing withdrawal symptoms, be started on Suboxone (buprenorphine/naloxone) induction or go straight to maintenance Suboxone (buprenorphine/naloxone)?
What are the adverse effects of buprenorphine and how should they be managed?
Can a patient take naltrexone and Subutex (buprenorphine) together?
Can a buprenorphine (opioid partial agonist) patch be used in opioid-dependent patients who are currently stable on medication?
Is it safe to use Suboxone (buprenorphine and naloxone) and Wellbutrin (bupropion) together in a 39-year-old female patient with a history of heroin abuse, currently stable on Suboxone, for anxiety and smoking cessation?
Should the amlodipine (10 mg) dose be reduced after six months of stable, target‑range hypertension?
Can hyperthyroidism cause excessive urination (polyuria)?
After excisional hemorrhoidectomy I have lost the rectal sensory cue I used for sleep, relaxation, and sexual arousal; what could be causing this neuropathic sensory loss and how should it be evaluated and managed?
What is the recommended treatment for a 17-year-old with uncomplicated genital Chlamydia trachomatis infection?
Should a patient with possession‑trance episodes be diagnosed with Dissociative Trance Disorder or schizophrenia, and what are the recommended treatments for each?
Does white bile seen during ERCP and biliary stenting indicate that the common bile duct obstruction has been present for weeks to months?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.