Buprenorphine and Lonafarnib: 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
Lonafarnib
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 me walk you through this one. Lonafarnib (Zokinvy) slows down a liver enzyme that normally helps break down buprenorphine (your pain or opioid-treatment medicine). When that enzyme is slowed, more buprenorphine can build up in your body. That can mean stronger opioid effects, like heavy drowsiness or slowed breathing.
On top of that, both drugs can affect your heart's rhythm, and together they may add up. This concern is mostly based on how the drugs work rather than lots of real-world reports, but because it involves breathing and heart rhythm, we take it seriously. The good news: your care team can manage this by adjusting your dose and watching you more closely. Please don't change anything on your own.
Effect: Lonafarnib inhibits CYP3A4, reducing buprenorphine clearance and increasing buprenorphine exposure, with additive QT prolongation and torsade de pointes risk. Neither is a prodrug here; buprenorphine's active parent accumulates.
- Direction: increased buprenorphine effect (sedation, respiratory depression) plus additive QT risk.
- Evidence: theoretical; severity major; onset unspecified.
- Management: Avoid combination where possible. If used together, obtain ECG monitoring, consider reducing the buprenorphine dose to stable effect, and monitor frequently for sedation/respiratory depression.
- On lonafarnib discontinuation, anticipate falling buprenorphine levels; consider dose increase and watch for withdrawal. Prefer formulations allowing precise titration.
What happens
Increased buprenorphine exposure, an increased risk of buprenorphine-related adverse events and an increased risk of QT interval prolongation and torsade de pointes
Interaction Deep Dive
Do not use lonafarnib together with buprenorphine, since the combination can produce additive prolongation of the QT interval. Perform ECG monitoring at the start of and throughout concurrent use3. Taking the two drugs together may also raise buprenorphine exposure and could prolong opioid effects, such as respiratory depression. Should concurrent use be required, consider lowering the buprenorphine dose until steady drug effects are reached, and frequently watch for sedation and respiratory depression. If lonafarnib is stopped in a patient on buprenorphine, consider raising the buprenorphine dose until stable drug effects are attained, and observe for signs of opioid withdrawal 2. When the dose cannot be modified without lonafarnib present, switch the patient back to a buprenorphine formulation that allows more precise dosing adjustments. For patients transitioned from transmucosal buprenorphine given alongside lonafarnib, verify that the plasma buprenorphine concentration achieved with subQ buprenorphine is sufficient. In patients who are already receiving subQ buprenorphine and who need lonafarnib, monitor for signs and symptoms of overdose. If buprenorphine toxicity or overdose signs and symptoms develop but the co-administered drug cannot be lowered or stopped, decrease the buprenorphine dose 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of buprenorphine; additive QT interval prolongation
How to manage this interaction
First, keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is usually avoided, but sometimes it is necessary, and it can be managed.
- Your team may order ECGs (heart tracings) when starting or continuing these together to watch your heart rhythm.
- Your buprenorphine dose may need to be adjusted and individualized, and your team may monitor you more closely for heavy drowsiness or slowed breathing.
- If lonafarnib is stopped later, your buprenorphine dose may need to be raised again, so watch for withdrawal symptoms.
Call your pharmacist or prescriber right away if you feel unusually sleepy, hard to wake, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in individuals receiving subQ buprenorphine has not been investigated; nevertheless, these 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 Lonafarnib together?
Combining lonafarnib and buprenorphine can raise buprenorphine levels (more sedation and slowed breathing) and add to heart-rhythm risk, so it is usually avoided; if used together, expect ECG checks, possible dose changes, and closer monitoring by your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Lonafarnib 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 Lonafarnib interaction managed?
First, keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is usually avoided, but sometimes it is necessary, and it can be managed. Your team may order ECGs (heart tracings) when starting or continuing these together to watch your heart rhythm. Your buprenorphine dose may need to be adjusted and individualized, and your team may monitor you more cl… 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 Buprenorphine or Lonafarnib 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
- Product Information: ZOKINVY(TM) oral capsules, lonafarnib oral capsules. Eiger BioPharmaceuticals Inc (per FDA), Palo Alto, CA, 2024. DailyMed
Keep reading about Buprenorphine
Keep reading about Lonafarnib
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