Clindamycin and Nirogacestat: 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
Clindamycin
Nirogacestat
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 with these two medicines. Nirogacestat (Ogsiveo) slows down a liver enzyme called CYP3A that your body uses to break down many drugs, including clindamycin. When that enzyme is blocked, clindamycin can build up higher than usual in your body, which may raise your chance of side effects like stomach upset, diarrhea, or other reactions.
The good news is that this is very manageable. Your care team knows about this interaction and can plan for it, whether that means choosing a different antibiotic, adjusting things, or watching you a little more closely. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor so they can guide you.
Effect: Nirogacestat inhibits CYP3A, reducing metabolism of CYP3A substrates and increasing their systemic exposure with a higher risk of substrate-related adverse effects.
- Direction: Increased clindamycin exposure (clindamycin is partly CYP3A4-metabolized).
- Magnitude: Not established for clindamycin. For midazolam (index CYP3A substrate), nirogacestat 150 mg BID is predicted to raise Cmax ~1.77-fold and AUC ~2.07-fold.
- Evidence / onset: Probable; onset unspecified.
- Management: Label advises avoiding concomitant use of nirogacestat with CYP3A substrates. Consider a non-CYP3A alternative antibiotic; if co-use is unavoidable, monitor closely for clindamycin-related adverse effects. Dose may need individualization by the care team.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse effects
Interaction Deep Dive
Do not administer nirogacestat together with CYP3A substrates. Because nirogacestat raises the exposure of CYP3A substrates, even small changes in their concentrations can produce serious adverse reactions. When taken alongside multiple doses of nirogacestat (150 mg twice daily), the Cmax of midazolam (a CYP3A substrate) is projected to rise by 1.77-fold and its AUC by 2.07-fold1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by nirogacestat
How to manage this interaction
What your care team may do:
- Consider whether a different antibiotic that isn't affected by nirogacestat would work for your infection.
- If both are needed, monitor you more closely for side effects such as GI upset or diarrhea.
- Adjust and individualize your therapy as appropriate for you.
What you should do:
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Tell your pharmacist or doctor you're on both drugs, and report any new or worsening side effects.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When taken together with repeated doses of nirogacestat (150 mg twice daily), the Cmax of midazolam (a CYP3A substrate) is projected to rise by 1.77-fold and its AUC by 2.07-fold 1.
Common questions
Can I take Clindamycin and Nirogacestat together?
Nirogacestat can raise clindamycin levels by blocking CYP3A, so the label advises avoiding this combination when possible. Don't change anything on your own; ask your pharmacist or doctor whether a different antibiotic is a better fit. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clindamycin and Nirogacestat 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 Clindamycin and Nirogacestat interaction managed?
What your care team may do: Consider whether a different antibiotic that isn't affected by nirogacestat would work for your infection. If both are needed, monitor you more closely for side effects such as GI upset or diarrhea. Adjust and individualize your therapy as appropriate for you. What you should do: Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise… 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 Clindamycin or Nirogacestat 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: OGSIVEO(TM) oral tablets, nirogacestat oral tablets. SpringWorks Therapeutics, Inc. (per FDA), Stamford, CT, 2023. DailyMed
Keep reading about Clindamycin
Keep reading about Nirogacestat
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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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