Selpercatinib 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
Selpercatinib
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.
Your cancer medicine selpercatinib (Retevmo) can gently slow down a liver enzyme (called CYP3A) that your body uses to break down clindamycin. When that clean-up slows a little, clindamycin can build up in your body and its side effects, like stomach upset or diarrhea, may become more noticeable.
I want to be clear that this concern is theoretical, meaning it is based on how these drugs behave rather than reports of problems in people. The good news is your care team can manage this easily by adjusting your dose if needed and keeping an eye on how you feel. Please don't change anything on your own, just check in with your doctor or pharmacist.
Mechanism: Selpercatinib is a weak CYP3A inhibitor; clindamycin is a CYP3A4 substrate. Inhibition may reduce clindamycin clearance, increasing exposure (AUC/Cmax) and adverse-effect risk. Neither agent's action is prodrug-dependent here, so the effect is a straightforward increase in substrate exposure.
- Direction: Increased clindamycin exposure and adverse effects (GI intolerance, diarrhea/C. difficile risk).
- Magnitude: Reference midazolam data showed AUC +54%, Cmax +39%; clindamycin-specific data not established.
- Onset: Unspecified.
- Evidence: Theoretical.
- Management: Avoid where minimal concentration changes matter; if necessary, consider substrate dose reduction and closer monitoring.
What happens
Increased substrate exposure and an increased risk for adverse effects
Interaction Deep Dive
Do not combine selpercatinib (a weak inhibitor of CYP3A) with any CYP3A substrate for which small shifts in concentration could trigger adverse reactions. A pharmacokinetic study demonstrated that giving midazolam (a sensitive CYP3A substrate) alongside selpercatinib raised midazolam AUC (0 to inf) by 54% and Cmax by 39%. When it is unavoidable to use selpercatinib together with such a CYP3A substrate, reducing the substrate dose as appropriate should be considered1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by selpercatinib
How to manage this interaction
Your care team can handle this safely. Depending on your situation, they may take steps such as:
- Adjusting and individualizing your clindamycin dose while you are also taking selpercatinib.
- Monitoring you more closely for side effects like diarrhea, cramping, or stomach upset.
- Sometimes choosing a different antibiotic if it makes sense for your treatment.
What you should do: keep taking both medicines exactly as prescribed unless your provider tells you otherwise. Let your pharmacist or doctor know if you develop worsening diarrhea or belly pain, and make sure they know you take both drugs.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic study, giving selpercatinib together with midazolam (a sensitive CYP3A substrate) raised the midazolam AUC (0 to inf) by 54% and the Cmax by 39% 1.
Common questions
Can I take Selpercatinib and Clindamycin together?
Selpercatinib can raise clindamycin levels a bit, so watch for more side effects like diarrhea; your care team may adjust the dose or monitor you more closely, so keep taking both as prescribed and report any problems. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib 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 Selpercatinib and Clindamycin interaction managed?
Your care team can handle this safely. Depending on your situation, they may take steps such as: Adjusting and individualizing your clindamycin dose while you are also taking selpercatinib. Monitoring you more closely for side effects like diarrhea, cramping, or stomach upset. Sometimes choosing a different antibiotic if it makes sense for your treatment. What you should do: keep taking both medic… 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 Selpercatinib 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: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Selpercatinib
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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