Omaveloxolone and Sertraline: 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
Omaveloxolone
Sertraline
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.
You're taking Skyclarys (omaveloxolone) along with sertraline, an antidepressant. Omaveloxolone can gently speed up one of the liver enzymes (called CYP3A4) that helps break down sertraline. In theory, that could clear sertraline out of your body a little faster and make it work a bit less well, so your mood or anxiety symptoms might not be as well controlled.
Here's the reassuring part: this is based on lab reasoning, not strong real-world reports, and omaveloxolone is only a weak booster of this enzyme. Just keep taking both exactly as prescribed and let your care team know how you're feeling. If needed, they can adjust your sertraline dose or watch your symptoms more closely.
Effect: Omaveloxolone is a weak CYP3A4 inducer and may increase metabolism of CYP3A4 substrates, reducing their exposure and efficacy. Sertraline is partly metabolized via CYP3A4 (along with CYP2C19, 2B6, 2D6 and others), so co-administration could modestly lower sertraline exposure.
- Direction: reduced sertraline effect (induction, not a prodrug issue).
- Magnitude: in a study, omaveloxolone reduced midazolam AUC ~45%; sertraline impact likely smaller given multiple metabolic pathways.
- Evidence: theoretical; onset: unspecified (induction is typically delayed).
- Management: monitor for loss of antidepressant efficacy; 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 acts as 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 at the same time, watch for reduced efficacy of that co-administered agent. A drug interaction study showed that coadministering omaveloxolone with midazolam (a CYP3A4 substrate) lowered the AUC of midazolam by roughly 45%1.
Why it happens (mechanism)
Induction of CYP3A4 substrate metabolism by omaveloxolone
How to manage this interaction
This interaction can be managed. Keep taking both omaveloxolone and sertraline as prescribed unless your prescriber tells you otherwise.
- Watch for reduced benefit from sertraline, such as returning low mood, anxiety, or worsening symptoms.
- Report any such changes to your pharmacist or prescriber, who can decide if your sertraline dose needs to be adjusted and individualized.
- Your care team may simply monitor you more closely for how well the antidepressant is working.
Do not start, stop, or change either medication on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study, coadministration of omaveloxolone with midazolam reduced the AUC of midazolam (a CYP3A4 substrate) by roughly 45% 1.
Common questions
Can I take Omaveloxolone and Sertraline together?
Omaveloxolone may slightly weaken sertraline's effect by speeding its breakdown, so watch for returning depression or anxiety symptoms and tell your care team, who can adjust the dose or monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omaveloxolone and Sertraline 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 Omaveloxolone and Sertraline interaction managed?
This interaction can be managed. Keep taking both omaveloxolone and sertraline as prescribed unless your prescriber tells you otherwise. Watch for reduced benefit from sertraline, such as returning low mood, anxiety, or worsening symptoms. Report any such changes to your pharmacist or prescriber, who can decide if your sertraline dose needs to be adjusted and individualized. Your care team may sim… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omaveloxolone or Sertraline 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 Omaveloxolone
Keep reading about Sertraline
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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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