Oliceridine and Esketamine Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Oliceridine
Esketamine Nasal Spray
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.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma and death
Interaction Deep Dive
Concomitant use of oliceridine (an opioid analgesic) with CNS depressants may increase the risk of hypotension, respiratory depression, profound sedation, coma, and death due to additive pharmacological effects. Reserve concomitant prescription of these drugs for use in patients for whom alternative treatment options are inadequate. If the decision is made to prescribe CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Monitor patients closely for signs and symptoms of respiratory depression and sedation1.
Why it happens (mechanism)
Additive CNS depression
Literature reports
1 report — tap to read
a) Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics 1.
Common questions
Can I take Oliceridine and Esketamine Nasal Spray together?
An increased risk of hypotension, respiratory depression, profound sedation, coma and death Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oliceridine and Esketamine Nasal Spray 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 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 Oliceridine or Esketamine Nasal Spray 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: OLINVYK® intravenous injection, oliceridine intravenous injection. Trevena Inc (per FDA), Chesterbrook, PA, 2026. DailyMed
Keep reading about Oliceridine
Keep reading about Esketamine Nasal Spray
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