Oliceridine 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
Oliceridine
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.
Oliceridine (Olinvyk) is a strong IV pain medicine used in hospitals, and sertraline is a common antidepressant. When they are used together, two things can happen. First, sertraline can slow down the liver enzyme that breaks down oliceridine, so more of the pain medicine can build up in your body. That can mean stronger effects like drowsiness or slowed breathing. Second, both drugs raise a brain chemical called serotonin, and too much can cause a reaction called serotonin syndrome (shivering, fast heartbeat, sweating, agitation, or confusion).
This is based mostly on theory, and your care team can manage it safely by watching you closely and adjusting your dose. Let them know if you feel unusually restless, feverish, or shaky.
Mechanism: Sertraline inhibits CYP2D6, reducing metabolism of the CYP2D6 substrate oliceridine, which increases oliceridine exposure. Additive serotonergic activity also raises serotonin syndrome risk. Oliceridine is active as given (not a prodrug), so inhibition increases, not decreases, its opioid effect.
- Direction: Increased oliceridine exposure and additive serotonergic effect.
- Severity/Evidence: Major; theoretical.
- Onset: Unspecified; watch at initiation and dose changes.
- Management: If co-administered, reduce oliceridine dose as needed and monitor for opioid toxicity (sedation, respiratory depression) and serotonin syndrome. Discontinue oliceridine if serotonin syndrome is suspected. An oliceridine dose increase may be needed if sertraline is stopped.
What happens
Increased oliceridine exposure, and an increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has occurred when oliceridine is taken together with other agents that influence the serotonergic neurotransmitter system, sertraline being one example. When such combined use is justified, the patient should be watched closely, particularly at the start of therapy and whenever the dose is changed. Should serotonin syndrome be suspected, stop oliceridine3. Because sertraline acts as a CYP2D6 inhibitor, giving it alongside a CYP2D6 substrate like oliceridine may raise oliceridine exposure. If the two must be given together, lower the oliceridine dose as needed; on the other hand, the oliceridine dose may have to be raised if sertraline is stopped1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of oliceridine; additive serotonergic effects
How to manage this interaction
If your team decides you need both, they can manage this safely. Here is what usually happens and what you can do.
- Your team may lower the oliceridine dose and individualize it, since sertraline can raise its levels.
- They will monitor you more closely, especially when starting oliceridine or changing the dose, for heavy sedation, slowed breathing, or signs of serotonin syndrome.
- If sertraline is later stopped, the oliceridine dose may need to be increased.
- Keep taking both as prescribed. Tell your nurse, pharmacist, or doctor right away if you feel very drowsy, agitated, shivery, feverish, or notice a racing heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In studies of drug interactions, PARoxetine produced the following effects on agents metabolized by CYP2D6. When given at 20 mg once daily to steady-state, PARoxetine raised the Cmax, AUC, and t(1/2) of a single 100 mg dose of desipramine by roughly 2-, 5-, and 3-fold, respectively. Among patients stabilized on risperiDONE 4 to 8 mg/day, PARoxetine 20 mg daily increased 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 with concurrent PARoxetine than with atomoxetine alone. Mean digoxin steady-state AUC fell by 15% when PARoxetine was present. In a study using propranolol 80 mg twice daily over 18 days, the steady-state plasma concentrations of propranolol remained unchanged during coadministration with PARoxetine 30 mg once daily for the final 10 days 2.
b) In postmarketing experience, cases of serotonin syndrome, a condition that can be life-threatening, have been reported with the concurrent use of opioids and serotonergic drugs 3.
Common questions
Can I take Oliceridine and Sertraline together?
Combining oliceridine with sertraline can raise oliceridine levels and the risk of serotonin syndrome, so your care team may lower the oliceridine dose and watch you closely. Keep taking both as prescribed and report agitation, fever, shivering, extreme drowsiness, or slowed breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oliceridine 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 Oliceridine and Sertraline interaction managed?
If your team decides you need both, they can manage this safely. Here is what usually happens and what you can do. Your team may lower the oliceridine dose and individualize it, since sertraline can raise its levels. They will monitor you more closely, especially when starting oliceridine or changing the dose, for heavy sedation, slowed breathing, or signs of serotonin syndrome. If sertraline is l… 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 Oliceridine 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 (3)
- 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.
- Product Information: OLINVYK(R) intravenous injection, oliceridine intravenous injection. Trevena Inc (per FDA), Chesterbrook, PA, 2023. DailyMed
Keep reading about Oliceridine
Keep reading about Sertraline
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