Levorphanol 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
Levorphanol
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.
Levorphanol is a strong opioid pain medicine, and sertraline is an antidepressant. Both can raise serotonin, a chemical messenger in your brain. When you take them together, serotonin can build up too much, which in rare cases leads to a reaction called serotonin syndrome.
Watch for things like agitation, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, or feeling confused. This is considered a possible risk rather than something that happens to everyone, and it is more likely when you first start or when a dose changes. Your care team can manage this safely by keeping an eye on you, so please talk with your pharmacist or doctor before making any changes.
Interaction: Additive serotonergic effects from levorphanol (an opioid with serotonergic activity) plus sertraline (an SSRI) may increase the risk of serotonin syndrome. Neither agent is a prodrug requiring activation; this is a pharmacodynamic, not pharmacokinetic, interaction, so the risk is additive rather than exposure-driven.
- Direction: increased serotonergic effect
- Severity: major; evidence: theoretical
- Onset: unspecified; risk highest at initiation and dose titration
Management: If coadministration is required, monitor for hyperthermia, autonomic instability, neuromuscular findings (clonus, hyperreflexia, rigidity), and mental status changes. Discontinue levorphanol if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
When levorphanol is given together with another serotonergic drug, serotonin syndrome can develop, since each of these medications acts on the serotonergic neurotransmitter system. Should the combined use of levorphanol with such an agent be necessary from a clinical standpoint, observe patients closely, particularly when therapy is being started and when doses are being modified. If serotonin syndrome is suspected, stop levorphanol1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Both medicines can raise serotonin, so your care team's main job is to watch you closely, especially when you first combine them or when a dose changes.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your doses may be adjusted and individualized by your care team, and they may monitor you more closely during startup and dose changes.
- Learn the warning signs: agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching or stiffness, or fever.
If you notice these symptoms, seek medical help promptly. Your doctor may stop the levorphanol if serotonin syndrome is suspected. Bring up any concerns with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Levorphanol and Sertraline together?
Taking levorphanol with sertraline can add up to raise serotonin and, rarely, cause serotonin syndrome. Keep taking both as prescribed, know the warning signs, and contact your care team if symptoms like agitation, fever, sweating, or muscle twitching appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levorphanol 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 Levorphanol and Sertraline interaction managed?
Both medicines can raise serotonin, so your care team's main job is to watch you closely, especially when you first combine them or when a dose changes. Keep taking both as prescribed unless your prescriber tells you otherwise. Your doses may be adjusted and individualized by your care team, and they may monitor you more closely during startup and dose changes. Learn the warning signs: agitation,… 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 Levorphanol 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 (1)
- Product Information: levorphanol tartrate oral tablets, levorphanol tartrate oral tablets. Sentynl Therapeutics Inc (per DailyMed), Solana Beach, CA, 2016. DailyMed
Keep reading about Levorphanol
Keep reading about Sertraline
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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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