Acetaminophen And Codeine and Levomilnacipran: 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
Levomilnacipran
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.
You've been prescribed two medicines that can each nudge up a brain chemical called serotonin. The codeine in your pain pill and levomilnacipran (an antidepressant) both act on serotonin, and using them together can, in rare cases, push it too high. This is called serotonin syndrome.
Warning signs include feeling agitated or restless, a fast heartbeat, sweating, shivering, shaky muscles, or a high fever. This is mostly a theoretical concern, so try not to worry. Your care team can manage it, especially by watching you closely when either dose starts or changes. If you notice those symptoms, call your doctor right away.
Interaction: Additive serotonergic effects between codeine (in acetaminophen/codeine) and levomilnacipran, an SNRI, may increase the risk of serotonin syndrome.
- Direction/mechanism: Pharmacodynamic additive serotonergic activity (not a CYP-based PK interaction).
- Severity: Major. Evidence: Theoretical. Onset: Unspecified; risk highest at initiation and dose escalation.
- Management: If co-use is required, monitor for autonomic instability, neuromuscular abnormality (clonus, hyperreflexia, tremor), and mental status changes. Discontinue codeine if serotonin syndrome is suspected and provide supportive care.
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. When such combined use is necessary, monitor the patient closely, especially when starting therapy and when doses are being modified. If serotonin syndrome is suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This is a manageable, mostly theoretical risk.
- Extra monitoring: Your care team may watch you more closely, especially when either drug is started or a dose is changed.
- Know the symptoms: agitation, confusion, fast heartbeat, high blood pressure, sweating, shivering, twitching muscles, or fever.
- Act early: Contact your pharmacist or doctor promptly if these appear; codeine may be stopped if serotonin syndrome is suspected.
Ask your pharmacist to review all your serotonergic medicines so the plan can be individualized for you.
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 Levomilnacipran together?
Combining codeine (in acetaminophen/codeine) with levomilnacipran can rarely raise serotonin too high; keep taking both as prescribed but watch for agitation, fast heartbeat, sweating, shivering, or muscle twitching, especially when starting or changing doses, and call your doctor if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Levomilnacipran 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 Levomilnacipran interaction managed?
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This is a manageable, mostly theoretical risk. Extra monitoring: Your care team may watch you more closely, especially when either drug is started or a dose is changed. Know the symptoms: agitation, confusion, fast heartbeat, high blood pressure, sweating, shivering, twitching muscles, or fever. Act early: Conta… 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 Levomilnacipran 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 Levomilnacipran
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