Samidorphan 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
Samidorphan
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.
These two medicines work against each other, so they should not be used together. Buprenorphine is an opioid that attaches to opioid receptors in your body to relieve pain or treat opioid dependence. Samidorphan is an opioid blocker. It sits on those same receptors and pushes the opioid off.
If you take them together, buprenorphine may stop working, and you could suddenly go into opioid withdrawal, which can feel very unpleasant (sweating, nausea, cramps, shaking). This is why the combination is not allowed. The good news is your care team can plan around this safely by allowing the right amount of time between the two drugs. Always tell your pharmacist and doctor every medicine you take.
Contraindicated combination. Samidorphan is an opioid receptor antagonist; buprenorphine is a partial mu-opioid agonist. Through competitive binding at opioid receptors, samidorphan blocks buprenorphine's agonist effect, reducing analgesic/therapeutic efficacy and risking precipitated acute withdrawal in opioid-dependent patients.
- Direction: reduced opioid effect (PD antagonism), not a metabolic interaction.
- Evidence: theoretical/mechanistic; severity rated contraindicated.
- Management: Before starting samidorphan, ensure a 7-day opioid-free interval (short-acting) or 14-day (long-acting; relevant for extended-release buprenorphine). If opioid analgesia/anesthesia is needed, discontinue samidorphan (>=5 days before elective procedures); emergency opioid use requires trained administration and monitoring in a resuscitation-equipped setting.
What happens
Decreased opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
Because samidorphan, an opioid antagonist, raises the likelihood of triggering acute opioid withdrawal in opioid-dependent patients, its combined use with an opioid or in individuals experiencing acute opioid withdrawal is contraindicated. Before samidorphan is started, patients should observe an opioid-free period of at least 7 days following their last dose of short-acting opioids and at least 14 days following their last dose of long-acting opioids. Should an emergency arise in which a patient receiving samidorphan needs opioids for anesthesia or analgesia, samidorphan should be stopped. In such cases, the opioid must be given by suitably trained personnel, and the patient must be adequately monitored in a location that is equipped and staffed to perform cardiopulmonary resuscitation. Within a non-emergency context, when a samidorphan-treated patient is anticipated to need opioid therapy (for example, for analgesia during or following an elective surgical procedure), samidorphan should be discontinued at least 5 days ahead of the opioid treatment1.
Why it happens (mechanism)
Competitive binding at opioid receptors
How to manage this interaction
This is a contraindicated pairing, so your care team will avoid overlapping them. Follow their plan closely rather than changing anything on your own.
- Keep an up-to-date list of every opioid you take and share it before samidorphan is started.
- Your team typically requires an opioid-free gap before starting samidorphan (about 7 days after short-acting opioids and 14 days after long-acting forms like extended-release buprenorphine).
- If you may need opioid pain relief (for example, planned surgery), samidorphan is usually stopped at least 5 days beforehand.
- Ask your pharmacist or prescriber before starting, stopping, or spacing either drug.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Samidorphan and Buprenorphine together?
Samidorphan blocks buprenorphine and can trigger opioid withdrawal, so the two should not be used together; your care team will use timed drug-free intervals to manage this safely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Samidorphan and Buprenorphine interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Samidorphan and Buprenorphine interaction managed?
This is a contraindicated pairing, so your care team will avoid overlapping them. Follow their plan closely rather than changing anything on your own. Keep an up-to-date list of every opioid you take and share it before samidorphan is started. Your team typically requires an opioid-free gap before starting samidorphan (about 7 days after short-acting opioids and 14 days after long-acting forms lik… 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 Samidorphan 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: LYBALVI(TM) oral tablets, olanzapine samidorphan oral tablets. Alkermes Inc (per manufacturer), Waltham, MA, 2021. DailyMed
Keep reading about Buprenorphine
Keep reading about Samidorphan
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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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