Levorphanol and Buprenorphine: 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
Buprenorphine
Levorphanol
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.
Let's talk about taking buprenorphine and levorphanol together. Both are strong pain medicines, but buprenorphine works differently. It's a 'partial' opioid, and it can actually block some of the effect of a full opioid like levorphanol. That means your levorphanol may not relieve pain as well, and in some cases your body can react as if it's going into withdrawal (things like sweating, chills, stomach upset, or feeling agitated).
There's also a smaller, more theoretical concern that both drugs can raise a brain chemical called serotonin, which in rare cases causes agitation, fast heartbeat, or shakiness. The good news is your care team can manage all of this. Please don't change anything on your own. Just talk with your doctor or pharmacist.
Effect: Buprenorphine (partial mu agonist / mixed agonist-antagonist) may antagonize the analgesia of levorphanol (full mu agonist) and precipitate opioid withdrawal. Additive serotonergic activity also raises theoretical risk of serotonin syndrome.
- Mechanism: competitive opioid receptor antagonism (PD interaction); additive serotonergic effects.
- Direction: reduced levorphanol effect; possible withdrawal; increased serotonin syndrome risk.
- Evidence: theoretical. Severity: major. Onset: unspecified.
- Management: avoid concomitant use. If serotonergic exposure is unavoidable, monitor closely during initiation/titration and discontinue if serotonin syndrome is suspected (hyperthermia, clonus, autonomic instability, agitation).
What happens
Reduced analgesic effect or precipitation of withdrawal symptoms, and an increased risk of serotonin syndrome
Interaction Deep Dive
Do not combine levorphanol with either a mixed opioid agonist/antagonist or a partial agonist opioid analgesic, because such combinations can diminish the analgesic effect of levorphanol and may trigger withdrawal symptoms. Furthermore, when levorphanol is given alongside other agents that act on the serotonergic system, monitor the patient closely, particularly at the start of therapy and during dose titration, since the likelihood of serotonin syndrome is elevated; if serotonin syndrome is suspected, stop treatment1.
Why it happens (mechanism)
Opioid receptor antagonism; additive serotonergic effects
How to manage this interaction
Here is how a care team usually handles this combination:
- This pairing is generally avoided because buprenorphine can blunt levorphanol's pain relief and may trigger withdrawal symptoms.
- If both are needed for a time, your team may monitor you closely, especially when either drug is started or the dose is changed.
- They watch for signs of serotonin problems (agitation, fast heartbeat, tremor, sweating, high fever) and will act quickly if these appear.
What you should do: keep taking both exactly as prescribed for now, and do not stop or adjust either one on your own. Contact your pharmacist or prescriber to review your pain plan, and seek help right away if you feel withdrawal symptoms or the symptoms listed above.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Levorphanol and Buprenorphine together?
Buprenorphine can reduce levorphanol's pain relief and may trigger withdrawal, plus a theoretical serotonin syndrome risk, so this combination is usually avoided. Do not change anything yourself; ask your doctor or pharmacist to review your pain plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levorphanol and Buprenorphine 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 Buprenorphine interaction managed?
Here is how a care team usually handles this combination: This pairing is generally avoided because buprenorphine can blunt levorphanol's pain relief and may trigger withdrawal symptoms. If both are needed for a time, your team may monitor you closely, especially when either drug is started or the dose is changed. They watch for signs of serotonin problems (agitation, fast heartbeat, tremor, sweat… 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 Levorphanol or Buprenorphine 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 Buprenorphine
Keep reading about Levorphanol
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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