Buprenorphine and Crizotinib: 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
Crizotinib
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. Crizotinib (Xalkori) is a cancer medicine that slows down a liver enzyme (called CYP3A4) that normally helps your body break down buprenorphine. When that enzyme is slowed, buprenorphine can build up in your blood. Higher levels mean stronger opioid effects, like more drowsiness and, in serious cases, slowed breathing.
On top of that, both drugs can affect your heart's rhythm (something called QT prolongation), so using them together can add to that risk. Please don't stop or change either medicine on your own. This is very manageable. Your care team can adjust your buprenorphine dose and watch you more closely to keep you safe.
Mechanism: Crizotinib is a moderate CYP3A4 inhibitor and reduces buprenorphine metabolism, increasing buprenorphine exposure (higher plasma concentrations). Neither drug is a prodrug here, so inhibition increases opioid effect. Additionally, both agents prolong the QT interval, producing additive PD risk.
Effect: Enhanced/prolonged opioid effects (sedation, respiratory depression) plus increased QTc prolongation risk. Evidence: probable; severity major; onset unspecified.
Management:
- Monitor ECG/QTc, sedation, and respiratory status frequently.
- Consider reducing buprenorphine dose until stable effects achieved.
- On crizotinib discontinuation, anticipate lower buprenorphine levels; watch for withdrawal and consider dose increase.
- Use a formulation permitting precise titration if needed.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Combining buprenorphine with a CYP3A4 inhibitor can raise buprenorphine plasma levels, potentially leading to extended opioid effects such as respiratory depression. The chance of QT prolongation also rises when drugs that alter cardiac conduction are given together. Should these agents be used concurrently, watch the patient carefully for the emergence of a prolonged QT interval. It may be appropriate to lower the buprenorphine dose until stable drug effects are reached, with frequent checks for sedation and respiratory depression. When a CYP3A4 inhibitor is stopped in a patient on buprenorphine, consider raising the buprenorphine dose until stable drug effects are attained, and observe for signs of opioid withdrawal2. If dose adjustment is not feasible once the CYP3A4 inhibitor is no longer present, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned from transmucosal buprenorphine given alongside CYP3A4 inhibitors, verify that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient. In patients already receiving subQ buprenorphine who need a CYP3A4 inhibitor, watch for indications of over-medication. If buprenorphine toxicity or overdose signs and symptoms appear yet the concomitant drug cannot be lowered or stopped, decrease the buprenorphine dose. When the available doses do not allow the intended dose to be reached, halt treatment and manage the patient with a buprenorphine formulation that permits more precise dose adjustments 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
The good news: your care team can manage this by tailoring your buprenorphine dose and watching you more closely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
What your team may do:
- Reduce your buprenorphine dose until your effects are steady.
- Check your heart rhythm (an ECG) and watch for excess sleepiness or slowed breathing.
- Adjust the dose again if the crizotinib is later stopped, watching for withdrawal signs.
Call your care team right away if you feel very drowsy, confused, dizzy, or notice slow or shallow breathing. Ask your pharmacist before adding any new medicine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study of healthy volunteers (N=12), giving oral buprenorphine together with voriconazole produced a significant rise in the mean AUC(0 to 18 hours) of buprenorphine by 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), in Cmax by 3.9-fold (from 0.057 to 0.22 ng/mL), in half-life (from 9.1 to 14.5 hours), and in urinary clearance (from 0.31 to 0.73 L/hr). Voriconazole likewise significantly raised exposure to the active metabolite, norbuprenorphine, by almost 4-fold for AUC(0 to 18 hours) and by 3.3-fold for Cmax, while lowering renal clearance (from 7.2 to 2.9 L/hr). Participants had mild dizziness and nausea during both phases. Subjects were given either placebo or voriconazole 400 mg twice daily on day 1 and 200 mg twice daily on days 2 to 5, followed by a 4-week washout period before crossing over to the alternate regimen. On the fifth day, every subject received a single oral dose of buprenorphine 0.2 mg, or 3.6 mg during the placebo phase 3.
b) The impact of concurrent CYP3A4 inhibitors on buprenorphine exposure in individuals receiving subQ buprenorphine has not been investigated; nevertheless, such interactions have been demonstrated in studies employing transmucosal buprenorphine. Buprenorphine's effects may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Crizotinib together?
Crizotinib can raise buprenorphine levels and both can affect heart rhythm, so this combination needs closer monitoring and possibly a lower buprenorphine dose set by your care team. Keep taking both as prescribed and report drowsiness or slow breathing right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Crizotinib 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 Buprenorphine and Crizotinib interaction managed?
The good news: your care team can manage this by tailoring your buprenorphine dose and watching you more closely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. What your team may do: Reduce your buprenorphine dose until your effects are steady. Check your heart rhythm (an ECG) and watch for excess sleepiness or slowed breathing. Adjust the dose again… 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 Buprenorphine or Crizotinib 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: 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
- Fihlman M, Hemmila T, Hagelberg NM, et al: Voriconazole greatly increases the exposure to oral buprenorphine. Eur J Clin Pharmacol 2018; 74(12):1615-1622. PubMed
Keep reading about Buprenorphine
Keep reading about Crizotinib
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