Tucatinib 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
Tucatinib
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 tucatinib (Tukysa) slows down a liver enzyme called CYP3A that helps break down many other drugs. Clindamycin is partly cleared by that same enzyme, so when you take both, clindamycin can build up higher than usual in your body. That could mean a greater chance of side effects, such as stomach upset or diarrhea.
The good news is this is very manageable. Your care team may lower your clindamycin dose or watch you more closely while you are on both. Please don't stop or change either medicine on your own. Just let your pharmacist or doctor know you take both so they can tailor things safely for you.
Mechanism: Tucatinib is a strong CYP3A4 inhibitor. Clindamycin is metabolized in part by CYP3A4, so concurrent use decreases clindamycin clearance and increases exposure (AUC/Cmax), raising toxicity risk.
Direction: Increased clindamycin effect/exposure. Evidence: Probable (tucatinib significantly raised midazolam AUC/Cmax in a clinical DDI study). Severity: Major. Onset: Unspecified.
- Avoid concomitant use where minimal concentration changes may cause serious toxicity.
- If coadministration is required, reduce the CYP3A substrate (clindamycin) dosage.
- Monitor for clindamycin-related adverse effects (GI toxicity, C. difficile risk).
What happens
Increased exposure to CYP3A substrate and risk of toxicity
Interaction Deep Dive
Do not combine tucatinib with any CYP3A substrate for which even small shifts in concentration could produce serious or life-threatening toxicities. During a clinical study, giving tucatinib together with midazolam (a CYP3A substrate) markedly raised both the AUC and Cmax of midazolam. Should coadministration be necessary, lower the dose of the CYP3A substrate1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by tucatinib
How to manage this interaction
This interaction is manageable with your care team's help.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may lower the clindamycin dose or choose an alternative, since tucatinib can raise clindamycin levels.
- They may monitor you more closely for side effects such as diarrhea or stomach problems.
- Tell your pharmacist and doctor that you take both, and report any new or worsening symptoms promptly.
Doses can be individualized, so let your care team make any changes for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical trial, giving a single 2 mg dose of midazolam (a CYP3A substrate with a narrow therapeutic index) together with tucatinib 300 mg twice daily at steady state produced a ratio of midazolam exposure with versus without tucatinib of 5.7 for AUC and 3 for Cmax 1.
Common questions
Can I take Tucatinib and Clindamycin together?
Tucatinib can raise clindamycin levels by blocking CYP3A metabolism, so your care team may lower the clindamycin dose or watch you closely; keep taking both as prescribed and report side effects. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tucatinib 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 Tucatinib and Clindamycin interaction managed?
This interaction is manageable with your care team's help. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may lower the clindamycin dose or choose an alternative, since tucatinib can raise clindamycin levels. They may monitor you more closely for side effects such as diarrhea or stomach problems. Tell your pharmacist and doctor that you take both, and report a… 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 Tucatinib 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: TUKYSA(TM) oral tablets, tucatinib oral tablets. Seattle Genetics Inc (per FDA), Bothell, WA, 2020. DailyMed
Keep reading about Tucatinib
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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