Perampanel 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
Perampanel
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 (an opioid used for pain or opioid use disorder) and perampanel (a seizure medicine) both calm down your brain and nervous system. When you take them together, those calming effects can add up. This can make you very sleepy, slow your breathing, or in serious cases cause you to pass out. Perampanel can already cause drowsiness and dizziness on its own, so the combination deserves care.
The good news is your care team can manage this safely. Please don't stop either medicine on your own. Talk with your doctor or pharmacist so they can pick the safest doses and watch you more closely if needed.
Mechanism: additive CNS depression. Buprenorphine (a partial mu-opioid agonist) combined with perampanel (an AMPA receptor antagonist with prominent sedative/CNS-depressant effects) produces overlapping pharmacodynamic depression. Neither is a prodrug; this is a PD, not PK, interaction.
- Direction/effect: increased sedation, respiratory depression, risk of profound sedation, coma, death.
- Severity: major. Evidence: probable. Onset: unspecified.
- Management: use lowest effective doses; monitor for respiratory depression and excessive sedation; avoid where feasible. Do not withhold MAT solely due to concomitant CNS depressant use, as untreated OUD carries greater risk.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the CNS depressant effects can combine, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is preferable to using them concurrently. Certain situations may warrant monitoring in a higher level of care or a taper. In other cases, it may be suitable to gradually withdraw a patient from a prescribed CNS depressant or reduce it to the lowest effective dose. When concurrent use cannot be avoided, exercise caution in monitoring and management, and think about alternative approaches for treating 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 example, medications for insomnia) face a heightened risk of death. Analysis of aggregate nationwide death certificate data spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death from concurrent CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs depress the central nervous system, so your care team will manage this thoughtfully rather than simply stopping treatment.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest effective dose of each, adjusted and individualized to you, and may monitor you more closely for slowed breathing or heavy sedation.
- Watch for unusual drowsiness, confusion, dizziness, or slow/shallow breathing, and seek urgent help if these occur.
- Tell your pharmacist or doctor about any other sedating medicines, alcohol, sleep aids, or anxiety medicines you take.
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 for insomnia) had a heightened risk of death. Among MAT-treated patients aged 18 to 50, researchers compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus periods without such therapy, over the interval from July 1, 2005 to December 31, 2012. 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 combined MAT and benzodiazepine treatment, but these figures were not regarded as statistically significant. Although the results also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality when MAT and non-benzodiazepines were coadministered, only the fatal overdose and all-cause mortality figures 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 against the non-benzodiazepine cohort because they did not adjust for the reason the drugs were used 3.
b) A study drawing on combined national death certificate data from 2010 to 2014 documented 3495 drug overdose deaths in 2014. Methadone together with other CNS depressants were commonly named as contributors to those deaths. Simultaneous 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 identified 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 total count of methadone-involved deaths was 10 times that of buprenorphine-involved deaths, though confounding factors and variations in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone remains unknown 3.
Common questions
Can I take Perampanel and Buprenorphine together?
Buprenorphine and perampanel both slow the brain and breathing, so together they raise the risk of heavy sedation and respiratory depression. Don't stop either on your own; ask your care team to use the lowest effective doses and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Perampanel 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 Perampanel and Buprenorphine interaction managed?
Both drugs depress the central nervous system, so your care team will manage this thoughtfully rather than simply stopping treatment. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest effective dose of each, adjusted and individualized to you, and may monitor you more closely for slowed breathing or heavy sedation. Watch for unusual drowsiness,… 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 Perampanel 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 Perampanel
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