Omeprazole 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
Lonafarnib
Omeprazole
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: Lonafarnib (Zokinvy) slows down a liver enzyme called CYP2C19, which is the same enzyme your body uses to break down omeprazole (Prilosec). When lonafarnib slows that cleanup, omeprazole can build up in your blood. In one study, omeprazole levels rose by about 28% to 60% when the two were taken together.
More omeprazole in your system can mean a higher chance of its side effects. This is worth taking seriously, but it's very manageable. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor, who can watch you a little more closely and adjust your omeprazole dose if needed.
Mechanism: Lonafarnib inhibits CYP2C19, reducing metabolism of omeprazole (a CYP2C19 substrate), increasing its exposure.
Magnitude: Omeprazole 40 mg single dose with lonafarnib 75 mg BID x5 days increased omeprazole Cmax ~28% and AUC ~60% in healthy subjects.
- Direction: Increased omeprazole exposure and substrate-related adverse effects.
- Severity/evidence: Major; probable substantiation.
- Onset: Unspecified.
- Management: Avoid concomitant use where possible. If unavoidable, monitor for adverse reactions and reduce the omeprazole dose as needed, individualized by the care team.
What happens
Increased CYP2C19 substrate exposure and an increased risk of CYP2C19 substrate-related adverse effects
Interaction Deep Dive
Concurrent administration of lonafarnib, a CYP2C19 inhibitor, with CYP2C19 substrates should be avoided because it can raise the exposure (both AUC and Cmax) of the CYP2C19 substrate, thereby heightening the potential for adverse reactions associated with that substrate. In healthy subjects, when a single 40 mg oral dose of omeprazole (a CYP2C19 substrate) was given alongside multiple oral doses of lonafarnib 75 mg twice daily over 5 days, omeprazole Cmax rose by 28% and its AUC by 60%. When such combined use cannot be avoided, watch for adverse reactions and lower the dose of the CYP2C19 substrate if necessary1.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism by lonafarnib
How to manage this interaction
What your care team may do:
- Prefer avoiding this combination when there is another option available.
- If both are needed, watch you more closely for omeprazole-related side effects.
- Lower your omeprazole dose if needed. The right dose can be adjusted and individualized by your team.
What you should do: Keep taking both exactly as prescribed unless told otherwise. Let your pharmacist or prescriber know you are on both, and report any new or bothersome symptoms so they can adjust things if needed.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical study in healthy subjects, a single oral dose of omeprazole 40 mg (a CYP2C19 substrate) was given together with multiple oral doses of lonafarnib 75 mg twice daily over 5 days, and the Cmax and AUC of omeprazole rose by 28% and 60%, respectively 1.
Common questions
Can I take Omeprazole and Lonafarnib together?
Lonafarnib can raise omeprazole levels by blocking the enzyme that clears it, so this combination is best avoided; if both are needed, your care team may monitor you more closely and lower the omeprazole dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole 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 Omeprazole and Lonafarnib interaction managed?
What your care team may do: Prefer avoiding this combination when there is another option available. If both are needed, watch you more closely for omeprazole-related side effects. Lower your omeprazole dose if needed. The right dose can be adjusted and individualized by your team. What you should do: Keep taking both exactly as prescribed unless told otherwise. Let your pharmacist or prescriber k… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole 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 (1)
- Product Information: ZOKINVY(TM) oral capsules, lonafarnib oral capsules. Eiger BioPharmaceuticals Inc (per FDA), Palo Alto, CA, 2024. DailyMed
Keep reading about Lonafarnib
Keep reading about Omeprazole
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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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