Lonafarnib and Clindamycin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lonafarnib
Clindamycin
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's talk about taking lonafarnib (Zokinvy) and clindamycin together. Lonafarnib slows down a liver enzyme called CYP3A that your body uses to break down many medicines, including clindamycin. When that enzyme is slowed, clindamycin can build up in your body a bit more than usual, which may make side effects like stomach upset or diarrhea more likely.
I want to be honest: this is based on how these drugs work in theory, not on a specific study of these two together, so it is a caution more than a certainty. Please don't stop or change either medicine on your own. Your care team can watch you closely and adjust things if needed. Just let them know you take both.
Mechanism: Lonafarnib is a CYP3A inhibitor; clindamycin is partly metabolized by CYP3A4. Inhibition can raise clindamycin exposure (increased Cmax/AUC), potentially increasing adverse effects.
Direction: Increased clindamycin effect/toxicity (neither drug is a prodrug here).
Magnitude/evidence: Theoretical for this pair. Reference midazolam data showed Cmax +180% and AUC +639% with lonafarnib 100 mg BID.
- Clindamycin is not a classic narrow-therapeutic-index agent, so risk is likely lower than for true NTI substrates.
- Monitor for GI toxicity (diarrhea, C. difficile risk) and other adverse reactions.
- Reduce clindamycin dose if clinically indicated per care team.
What happens
Increased CYP3A substrate with NTI exposure and an increased risk of CYP3A substrate with NTI-related serious or life-threatening toxicities
Interaction Deep Dive
Taking lonafarnib (which inhibits CYP3A) together with a CYP3A substrate that has a narrow therapeutic index (NTI) can raise exposure to that NTI substrate and may result in serious or life-threatening toxicities. In a clinical study involving healthy subjects, a single 3 mg oral dose of midazolam (a CYP3A substrate) was given alongside repeated oral doses of lonafarnib 100 mg twice daily over 5 days, producing increases in midazolam Cmax of 180% and in AUC of 639%. Watch for adverse reactions and lower the dose of the CYP3A substrate with NTI as needed1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by lonafarnib
How to manage this interaction
Here is how your care team typically handles this:
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely for side effects such as diarrhea, stomach pain, or nausea.
- If needed, your clindamycin dose may be adjusted and individualized by your care team.
What to raise: Tell your pharmacist or prescriber you take both drugs, and report any new or worsening diarrhea (especially severe or bloody), belly pain, or fever promptly. This is manageable with a little extra attention.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical study where a single 3 mg oral dose of midazolam (a CYP3A substrate) was given together with repeated oral doses of 100 mg lonafarnib twice daily over 5 days in healthy subjects, the Cmax and AUC of midazolam rose by 180% and 639%, respectively 1.
Common questions
Can I take Lonafarnib and Clindamycin together?
Lonafarnib can slow the breakdown of clindamycin, so clindamycin levels and side effects (like diarrhea) may rise; keep taking both as prescribed and let your care team monitor you and adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lonafarnib and Clindamycin 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 Lonafarnib and Clindamycin interaction managed?
Here is how your care team typically handles this: Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely for side effects such as diarrhea, stomach pain, or nausea. If needed, your clindamycin dose may be adjusted and individualized by your care team. What to raise: Tell your pharmacist or prescriber you take both drugs,… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Lonafarnib or Clindamycin 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 Clindamycin
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.
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