Acetaminophen And Codeine and Vilazodone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Vilazodone
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 have been prescribed two medicines that can both nudge up a brain chemical called serotonin. Your pain medicine contains codeine, and vilazodone (Viibryd) is an antidepressant. When two serotonin-raising drugs are used together, there is a small chance of a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or restless, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, and confusion. This is considered a possible risk rather than something that happens to everyone. The good news is your care team can manage this by keeping an eye on you, especially when you first start or change a dose. Keep taking both as prescribed and call your doctor right away if these symptoms show up.
Effect: Additive serotonergic activity from codeine (mu-opioid agonist with weak serotonergic properties) plus vilazodone (SSRI/5-HT1A partial agonist) may increase the risk of serotonin syndrome.
- Direction: Additive pharmacodynamic effect; both agents raise serotonergic tone.
- Severity/evidence: Rated major, but substantiation is theoretical; onset unspecified.
- Monitoring: Observe for agitation, hyperthermia, tachycardia, diaphoresis, tremor, clonus, hyperreflexia, and mental status changes, particularly at initiation and dose changes.
- Management: Concomitant use may proceed with vigilance; discontinue codeine if serotonin syndrome is suspected and treat supportively.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like codeine are taken together with serotonergic agents. Should combined therapy be required, monitor the patient closely, especially when initiating treatment and when doses are being changed. If serotonin syndrome is suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Both medicines can be used together when needed, but your care team will watch you a bit more closely.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Extra attention is most important when you first start either drug or when a dose is changed.
- Learn the warning signs: restlessness, fast heartbeat, sweating, shivering, muscle twitching or stiffness, fever, or confusion.
- If those symptoms appear, contact your prescriber right away, as the codeine may be stopped.
Ask your pharmacist or doctor before adding any other serotonin-affecting medicine, including over-the-counter or herbal products.
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 Vilazodone together?
Codeine and vilazodone can both raise serotonin, so together there is a possible (though theoretical) risk of serotonin syndrome. Take both as prescribed, watch for symptoms like agitation, fast heartbeat, sweating, or muscle twitching, and call your doctor if they appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Vilazodone 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 Vilazodone interaction managed?
Both medicines can be used together when needed, but your care team will watch you a bit more closely. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Extra attention is most important when you first start either drug or when a dose is changed. Learn the warning signs: restlessness, fast heartbeat, sweating, shivering, muscle twitching or stiffness, fever, or confusi… 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 Vilazodone 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 Vilazodone
These medications also interact with supplements
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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