Ceritinib 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
Ceritinib
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.
Taking buprenorphine (a pain or addiction medicine) together with ceritinib (Zykadia, a cancer medicine) can cause two problems worth knowing about. First, ceritinib slows down the liver enzyme that clears buprenorphine, so more buprenorphine can build up in your body. That can mean stronger, longer-lasting opioid effects like sleepiness, slow or shallow breathing, and dizziness.
Second, both drugs can affect your heart's rhythm (called QT prolongation), and together that risk goes up. This sounds serious, and it can be, but your care team can manage it with heart tracings (ECGs), monitoring, and dose adjustments. Please don't stop or change either medicine on your own, talk with your doctor or pharmacist first.
Direction/mechanism: Ceritinib is a CYP3A4 inhibitor; buprenorphine is a CYP3A4 substrate (not a prodrug requiring activation). Inhibition increases buprenorphine exposure, prolonging opioid effects and increasing risk of respiratory depression, sedation, and other opioid adverse events. Both agents also independently prolong the QT interval, giving additive QTc effects.
- Severity/evidence: Major; probable substantiation. Onset unspecified.
- Monitoring: Baseline and periodic ECG/QTc; monitor for opioid toxicity (sedation, hypoventilation).
- Management: Avoid combination if possible. Withhold, reduce, or discontinue ceritinib per QTc thresholds. If buprenorphine toxicity occurs and ceritinib cannot be stopped, reduce buprenorphine dose; on inhibitor discontinuation, monitor for withdrawal and consider dose increase. Consider a formulation allowing precise titration.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Using ceritinib together with any other agent that prolongs the QT interval can produce additive prolongation effects and should therefore be avoided. When such combined use occurs, monitor ECGs. Depending on clinical requirements, ceritinib may need to be withheld, reduced in dose, or stopped permanently in response to QTc interval prolongation3. Combining buprenorphine with a CYP3A4 inhibitor can raise buprenorphine exposure and potentially cause prolonged opioid effects. For patients switched from a transmucosal buprenorphine regimen given alongside CYP3A4 inhibitors, confirm that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient by monitoring them. For patients who are already receiving subQ buprenorphine and who need a CYP3A4 inhibitor, watch for indications of over-medication. Should signs and symptoms of buprenorphine toxicity develop while the accompanying drug cannot be lowered or stopped, decrease the buprenorphine dose. If the available doses make it impossible to reach the intended dose, halt treatment and manage the patient using a buprenorphine formulation that allows finer dose adjustments. Upon stopping a CYP3A4 inhibitor in a patient on buprenorphine, consider raising the buprenorphine dose until steady drug effects are reached, and observe for indications of opioid withdrawal. If the dose cannot be modified once the CYP3A4 inhibitor is gone, move the patient back to a buprenorphine formulation that permits more precise dose adjustments1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Both medicines can be used together when your care team plans for it. Here is what that usually looks like:
- Your team may check your heart rhythm with ECGs before and during treatment, since both drugs can affect the QT interval.
- They will watch for signs your buprenorphine level is too high (unusual drowsiness, confusion, slow or shallow breathing).
- Your buprenorphine dose may need to be adjusted and individualized by your care team, and monitored more closely while you are on ceritinib.
- When ceritinib is stopped, they may watch for opioid withdrawal and adjust your buprenorphine dose again.
Keep taking both as prescribed and raise any new symptoms with your pharmacist or prescriber right away.
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, increasing it 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), Cmax by 3.9-fold (from 0.057 to 0.22 ng/mL), half-life (from 9.1 to 14.5 hours), and urinary clearance (from 0.31 to 0.73 L/hr). Voriconazole likewise significantly raised exposure to the active metabolite, norbuprenorphine, by nearly 4-fold for AUC (0 to 18 hours) and by 3.3-fold for Cmax, and lowered renal clearance (from 7.2 to 2.9 L/hr). Participants reported mild dizziness and nausea in both phases. Subjects were given either placebo or voriconazole 400 mg twice daily on day 1, then 200 mg twice daily on days 2 to 5, followed by a 4-week washout period before switching over to the alternative regimen. On the fifth day, every subject received a single dose of buprenorphine 0.2 mg orally, or 3.6 mg during the placebo phase 2.
b) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in subjects treated with subQ buprenorphine has not been investigated; nevertheless, such interactions have been documented in studies employing transmucosal buprenorphine. The effects of buprenorphine may depend on the route of administration 1.
Common questions
Can I take Ceritinib and Buprenorphine together?
Combining buprenorphine and ceritinib can raise buprenorphine levels (more opioid side effects) and add to QT (heart rhythm) risk, so this pairing should be avoided when possible and needs ECG checks and close monitoring. Do not change either medicine on your own; talk with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ceritinib 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 Ceritinib and Buprenorphine interaction managed?
Both medicines can be used together when your care team plans for it. Here is what that usually looks like: Your team may check your heart rhythm with ECGs before and during treatment, since both drugs can affect the QT interval. They will watch for signs your buprenorphine level is too high (unusual drowsiness, confusion, slow or shallow breathing). Your buprenorphine dose may need to be adjusted… 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 Ceritinib 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 (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 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
- Product Information: ZYKADIA(R) oral capsules, oral tablets, ceritinib oral capsules, oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2019. DailyMed
Keep reading about Buprenorphine
Keep reading about Ceritinib
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist