Buprenorphine and Omaveloxolone: 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
Omaveloxolone
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.
You've been prescribed buprenorphine (a medicine for pain or opioid treatment) along with omaveloxolone (Skyclarys). Omaveloxolone can gently speed up the liver enzyme that breaks down buprenorphine. That means your body may clear the buprenorphine a bit faster, so it could work less well than expected. For someone on buprenorphine, that might show up as pain returning or withdrawal-type feelings.
The good news is this is expected and manageable. Don't change anything on your own. Just let your care team know you take both, and they can watch how well your buprenorphine is working and adjust it if needed.
Effect: Omaveloxolone is a weak CYP3A4 inducer; buprenorphine is a CYP3A4 substrate. Coadministration may increase buprenorphine metabolism, lowering its exposure (AUC/Cmax) and potentially reducing analgesic or maintenance efficacy.
- Direction: reduced buprenorphine effect (induction, not a prodrug scenario).
- Magnitude: extrapolated from midazolam study (~45% AUC decrease); buprenorphine-specific data not available.
- Onset: unspecified; induction typically develops over days.
- Evidence: theoretical.
- Management: monitor for loss of efficacy (return of pain, withdrawal symptoms); dose may be individualized by the care team.
What happens
Reduced CYP3A4 substrate exposure and reduced efficacy of CYP3A4 substrate
Interaction Deep Dive
Taking omaveloxolone, which is a weak inducer of CYP3A4, together with CYP3A4 substrates can lower the exposure of those substrates, potentially diminishing their effectiveness. When a CYP3A4 substrate is given alongside omaveloxolone, watch for reduced efficacy of that co-administered therapy. A drug interaction study demonstrated that co-administering omaveloxolone with midazolam (a CYP3A4 substrate) lowered midazolam's AUC by roughly 45%1.
Why it happens (mechanism)
Induction of CYP3A4 substrate metabolism by omaveloxolone
How to manage this interaction
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. This interaction is usually handled by watching how well your buprenorphine is working.
- Tell your pharmacist and prescriber that you take both drugs.
- Watch for signs your buprenorphine may be working less well, such as returning pain or withdrawal-type symptoms.
- Report those symptoms rather than adjusting your dose yourself.
- Your buprenorphine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study examining drug interactions, coadministration of omaveloxolone with midazolam reduced the AUC of midazolam (a CYP3A4 substrate) by roughly 45% 1.
Common questions
Can I take Buprenorphine and Omaveloxolone together?
Omaveloxolone may make buprenorphine work a bit less well by speeding up how your body clears it, so watch for returning pain or withdrawal symptoms and tell your care team, who can adjust and monitor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Omaveloxolone 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 Omaveloxolone interaction managed?
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. This interaction is usually handled by watching how well your buprenorphine is working. Tell your pharmacist and prescriber that you take both drugs. Watch for signs your buprenorphine may be working less well, such as returning pain or withdrawal-type symptoms. Report those symptoms rather than adjustin… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Buprenorphine or Omaveloxolone 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 (1)
- Product Information: Skyclarys® oral capsules, omaveloxolone oral capsules. Biogen U.S. Corporation, Cambridge, MA, 2026. DailyMed
Keep reading about Buprenorphine
Keep reading about Omaveloxolone
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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