Sertraline and Valbenazine: 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
Sertraline
No brand names on recordValbenazine
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.
Here's what's going on. Sertraline (an antidepressant) can slow down one of the liver enzymes (called CYP2D6) that helps your body break down valbenazine (Ingrezza), the medicine used for tardive dyskinesia. When that enzyme is slowed, more of the active form of valbenazine can build up in your body. That may make its side effects, like sleepiness or a feeling of being off-balance, more noticeable.
The good news: this is something your care team can plan for. They may fine-tune your valbenazine dose or keep a closer eye on how you're feeling. Please don't stop or change either medicine on your own. Just check in with your pharmacist or doctor.
Mechanism: Sertraline inhibits CYP2D6, reducing metabolism of valbenazine's active metabolite, which is partly CYP2D6-dependent. Expected result is increased valbenazine (active metabolite) exposure (AUC/Cmax) and greater risk of dose-related effects (somnolence, QT prolongation).
- Direction: increased CYP2D6 substrate exposure
- Evidence: theoretical
- Onset: unspecified
- Severity on file: major
Management: If coadministered, consider reducing valbenazine dose per labeling and monitor for adverse effects. On sertraline discontinuation, valbenazine dose may need to be increased back. Individualize dosing and monitor clinically.
What happens
Increased CYP2D6 substrate exposure
Interaction Deep Dive
When sertraline, which inhibits CYP2D6, is taken together with a substrate of CYP2D6, exposure to that substrate can rise. Should the two need to be given together, lower the CYP2D6 substrate dose as appropriate; on the other hand, stopping sertraline may call for raising the dose of the CYP2D6 substrate1.
Why it happens (mechanism)
Inhibition of CYP2D6 substrate metabolism by sertraline
How to manage this interaction
What your care team may do:
- Adjust and individualize your valbenazine (Ingrezza) dose, since sertraline can raise its levels. They may use a lower dose while you are on both.
- Monitor you more closely for side effects such as drowsiness or feeling unsteady.
- Revisit the dose if sertraline is later stopped, as valbenazine may then need to go back up.
What you should do: Keep taking both medicines exactly as prescribed. Tell your pharmacist or prescriber about any new drowsiness, dizziness, or other symptoms, and confirm the plan before making any change.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction studies, PARoxetine showed the following effects on medications metabolized by CYP2D6. PARoxetine 20 mg once daily at steady-state raised the Cmax, AUC, and t(1/2) of a single 100 mg dose of desipramine by roughly 2-, 5-, and 3-fold, respectively. In patients maintained on risperiDONE 4 to 8 mg/day, PARoxetine 20 mg daily increased the mean plasma concentrations of risperiDONE by 4-fold, reduced 9-hydroxyrisperiDONE concentrations by 10%, and raised concentrations of the active moiety by 1.4-fold. In healthy volunteers who were extensive CYP2D6 metabolizers, steady-state atomoxetine AUC values were 6- to 8-fold higher and Cmax values were 3- to 4-fold higher when PARoxetine was given concomitantly compared with atomoxetine alone. Mean digoxin steady-state AUC fell by 15% in the presence of PARoxetine. In a study using propranolol 80 mg twice daily for 18 days, the steady-state plasma concentrations of propranolol were unchanged during coadministration with PARoxetine 30 mg once daily over the final 10 days 2.
Common questions
Can I take Sertraline and Valbenazine together?
Sertraline can raise valbenazine levels by slowing its CYP2D6-based breakdown, so your care team may lower the valbenazine dose and watch you more closely; keep taking both as prescribed and report new side effects. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Valbenazine 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 Sertraline and Valbenazine interaction managed?
What your care team may do: Adjust and individualize your valbenazine (Ingrezza) dose, since sertraline can raise its levels. They may use a lower dose while you are on both. Monitor you more closely for side effects such as drowsiness or feeling unsteady. Revisit the dose if sertraline is later stopped, as valbenazine may then need to go back up. What you should do: Keep taking both medicines exa… 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 Sertraline or Valbenazine 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 (2)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.
Keep reading about Sertraline
Keep reading about Valbenazine
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