Gabapentin Enacarbil 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
Gabapentin Enacarbil
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.
Both of these medicines calm your nervous system. Buprenorphine (like Belbuca or Sublocade) is an opioid, and gabapentin enacarbil (Horizant) also has a calming effect on the brain. When you take them together, those effects can add up. That means you may feel more drowsy or foggy than usual, and in some cases your breathing can slow down too much, which is the part we take seriously.
The good news is that this is very manageable. Please keep taking both exactly as prescribed and do not stop either one on your own. Let your doctor or pharmacist know you take both so they can watch the doses closely and keep you safe.
Mechanism: Additive CNS depression. Buprenorphine (a partial opioid agonist) and gabapentin enacarbil (an active gabapentin prodrug that provides gabapentinoid CNS depressant activity) together potentiate sedation and respiratory depression. This is a pharmacodynamic, not pharmacokinetic, interaction; neither alters the other's metabolism.
- Direction/effect: Increased sedation, profound CNS depression, respiratory depression, potentially coma or death.
- Evidence: Probable; epidemiologic overdose-death data support risk.
- Severity: Major. Onset unspecified.
- Management: Use lowest effective doses, monitor for respiratory depression and sedation. Do not withhold MAT; consider alternatives for anxiety/insomnia where relevant.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effect can produce additive CNS depression, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored over using the two together. Depending on the situation, either observation in a higher level of care or a taper may be warranted. For some patients, slowly tapering them off a prescribed CNS depressant, or reducing it to the lowest dose that remains effective, may be suitable. When the combination cannot be avoided, exercise caution in monitoring and management, and weigh alternative approaches for managing anxiety or insomnia2. 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) face a heightened risk of death. Based on an analysis of pooled nationwide death certificate data covering 2010 to 2014, most overdose deaths involving buprenorphine or methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose associated with concomitant CNS depressants varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely by tailoring your treatment. Here is what that usually looks like:
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either one abruptly on your own.
- Your team may use the lowest effective dose and adjust or individualize your doses.
- They may monitor you more closely for excess drowsiness or slowed, shallow breathing.
- Ask your pharmacist or prescriber whether an alternative is appropriate if the gabapentin is for anxiety or sleep.
Seek urgent help for severe sleepiness, confusion, or trouble breathing.
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, agents used to treat insomnia) had a higher risk of death. From July 1, 2005 through December 31, 2012, investigators compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus periods without CNS depressant therapy in MAT-treated patients (aged 18 to 50). The findings showed an increased 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 plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated a higher risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, 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 of the drugs 3.
b) A study of aggregate nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone together with other CNS depressants were often listed 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 count of methadone-involved deaths was 10 times that of buprenorphine-involved deaths, although 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 3.
Common questions
Can I take Gabapentin Enacarbil and Buprenorphine together?
Taking buprenorphine and gabapentin enacarbil together can add up to dangerous drowsiness and slowed breathing, so keep both at the lowest effective doses and stay in close contact with your care team. Get emergency help if breathing slows or you cannot stay awake. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Gabapentin Enacarbil 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 Gabapentin Enacarbil and Buprenorphine interaction managed?
Your care team can manage this safely by tailoring your treatment. Here is what that usually looks like: Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either one abruptly on your own. Your team may use the lowest effective dose and adjust or individualize your doses. They may monitor you more closely for excess drowsiness or slowed, shallow breathing. Ask y… 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 Gabapentin Enacarbil 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 (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- 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 Gabapentin Enacarbil
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