Acetaminophen And Codeine and Vortioxetine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Vortioxetine
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.
Your pain medicine contains codeine, and vortioxetine (Trintellix) is an antidepressant. Both can raise a brain chemical called serotonin. When two medicines do that at the same time, there is a small chance of a reaction called serotonin syndrome.
Signs can include feeling agitated or confused, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, and sometimes shaking. This is uncommon, and the risk is highest when you first start a medicine or change a dose. The good news is your care team can manage this safely by watching how you feel. If you notice these symptoms, especially early on, reach out to your pharmacist or doctor right away.
Effect: Additive serotonergic activity may increase the risk of serotonin syndrome when codeine is combined with vortioxetine, an SSRI-like multimodal serotonergic agent.
- Mechanism: Pharmacodynamic (additive), not a clearance-based CYP interaction. Codeine and other opioids have documented serotonergic properties.
- Direction/magnitude: Increased CNS serotonergic tone; magnitude not quantified.
- Onset: Unspecified; risk greatest at initiation and dose changes.
- Evidence: Theoretical, severity rated major.
- Management: If co-use is needed, monitor for autonomic instability, neuromuscular abnormalities (clonus, hyperreflexia, rigidity), and mental status changes. Discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Cases of serotonin syndrome have been documented when opioids like codeine are taken together with serotonergic agents. When such combined use cannot be avoided, monitor the patient closely, especially while starting therapy and when doses are being changed. Should serotonin syndrome be suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
If both medicines are prescribed together, keep taking them as directed unless your prescriber tells you otherwise. Your care team can manage this safely.
- Expect closer monitoring when you start either drug or change a dose, since that is when risk is highest.
- Know the warning signs: agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching or stiffness, or tremor.
- Speak up early if these appear, contact your pharmacist or doctor promptly.
- Ask your care team before adding any new medicine that affects mood or pain.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Vortioxetine together?
Combining codeine with vortioxetine can slightly raise the risk of serotonin syndrome, so watch for symptoms like agitation, fast heartbeat, sweating, or muscle twitching, especially when starting or adjusting doses, and call your pharmacist or doctor if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Vortioxetine 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 Acetaminophen And Codeine and Vortioxetine interaction managed?
If both medicines are prescribed together, keep taking them as directed unless your prescriber tells you otherwise. Your care team can manage this safely. Expect closer monitoring when you start either drug or change a dose, since that is when risk is highest. Know the warning signs: agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching or stiffness, or tremor. Speak up early… 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 Acetaminophen And Codeine or Vortioxetine 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: Codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp (per DailyMed), Eatontown, NJ, 2016. DailyMed
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Vortioxetine
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