Lorlatinib 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
Lorlatinib
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.
Here's what's going on. Lorlatinib (Lorbrena) speeds up the enzyme in your liver that breaks down buprenorphine. When buprenorphine is cleared out faster, its level in your blood drops, so it may not work as well for you.
If you take buprenorphine for pain or for opioid use disorder, this could mean your usual dose feels weaker, and you might notice withdrawal-type feelings like body aches, chills, sweating, a runny nose, or feeling restless and anxious. The good news is that your care team can manage this by tailoring your buprenorphine dose and watching how you're doing. Don't change anything on your own, but please tell your pharmacist or doctor if you start feeling withdrawal.
Mechanism: Lorlatinib induces CYP3A4, increasing the metabolism of buprenorphine (a CYP3A4 substrate). Net effect is reduced buprenorphine exposure and reduced efficacy, risking opioid withdrawal. Neither agent's effect here depends on prodrug activation.
- Direction: decreased buprenorphine plasma concentration/AUC.
- Severity/evidence: major; probable substantiation. Onset unspecified.
- Management: If the inducer is needed, titrate buprenorphine upward to stable effect and monitor for withdrawal. On inducer discontinuation, consider dose reduction and monitor for respiratory depression. Prefer formulations allowing precise titration; for subQ depot products, verify adequate levels.
What happens
Reduced buprenorphine exposure and reduced efficacy of buprenorphine
Interaction Deep Dive
Because a CYP3A4 inducer can lower plasma buprenorphine concentrations, taking one alongside buprenorphine may bring on opioid withdrawal symptoms. When a patient on buprenorphine must also receive a CYP3A4 inducer, one option is to raise the buprenorphine dose until stable drug effects are reached while watching for withdrawal. Conversely, if a CYP3A4 inducer is stopped in a patient being treated with buprenorphine, consider lowering the buprenorphine dose and observe for respiratory depression2. When the dosage cannot be adjusted once the CYP3A4 inducer is gone, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients being converted from transmucosal buprenorphine given together with CYP3A4 inducers, verify that the plasma buprenorphine level achieved with subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who then need a CYP3A4 inducer, monitor for withdrawal. Should the buprenorphine dose prove inadequate while the concomitant drug is present, and that concomitant drug cannot be decreased or stopped, modify the buprenorphine dose. If the available doses do not allow the target dose to be reached, use a buprenorphine formulation that permits more precise dose adjustments1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medications as prescribed unless your care team tells you otherwise. Here is how a team typically handles this:
- Your buprenorphine dose may need to be adjusted and individualized to keep it working while you are on lorlatinib.
- Your team may monitor you more closely for withdrawal signs (aches, chills, sweating, restlessness).
- If lorlatinib is later stopped, your buprenorphine dose may be lowered, and you'll be watched for over-sedation or slowed breathing.
- A formulation that allows finer dose changes may be used if needed.
Tell your pharmacist or prescriber promptly if you feel withdrawal or notice your medication working less well.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of a concurrently administered CYP3A4 inducer on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, these interactions have been demonstrated in studies employing transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
Common questions
Can I take Lorlatinib and Buprenorphine together?
Lorlatinib can lower buprenorphine levels and trigger withdrawal, so your care team may adjust your buprenorphine dose and monitor you more closely. Keep taking both as prescribed and report any withdrawal symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lorlatinib 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 Lorlatinib and Buprenorphine interaction managed?
Keep taking both medications as prescribed unless your care team tells you otherwise. Here is how a team typically handles this: Your buprenorphine dose may need to be adjusted and individualized to keep it working while you are on lorlatinib. Your team may monitor you more closely for withdrawal signs (aches, chills, sweating, restlessness). If lorlatinib is later stopped, your buprenorphine dose… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Lorlatinib 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 (2)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Lorlatinib
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