Apixaban and Tucatinib: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Aug 8, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tucatinib
Apixaban
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.
Tucatinib (Tukysa) is a cancer medicine, and apixaban (Eliquis) is a blood thinner. Tucatinib slows down the way your body breaks down and clears apixaban, so more of the blood thinner can build up in your system. That can raise your chance of bleeding, like easy bruising, nosebleeds, or bleeding that is hard to stop.
The good news is your care team knows how to handle this. Depending on your apixaban dose, they may lower it or choose a different plan while you are on tucatinib. Please don't change anything on your own. Just check in with your doctor or pharmacist so they can keep both medicines working safely for you.
Effect: Increased apixaban exposure and bleeding risk.
Mechanism: Tucatinib is a combined strong CYP3A4 and P-gp inhibitor. Apixaban is a substrate of both CYP3A4 and P-gp (not a prodrug), so inhibition reduces its clearance and raises exposure. Reference data (ketoconazole) showed apixaban Cmax +62% and AUC +97%.
Evidence: Probable. Severity: Major.
Management:
- Avoid concomitant use when apixaban is dosed at 2.5 mg PO BID.
- For higher doses (5 or 10 mg BID), reduce apixaban by 50% during co-administration.
- Monitor for signs and symptoms of bleeding.
What happens
Increased apixaban exposure and an increased risk of bleeding
Interaction Deep Dive
In patients taking apixaban at 2.5 mg orally twice daily, steer clear of concurrent administration. For patients on higher apixaban regimens (that is, 5 or 10 mg twice daily), reduce the dose by 50% when a combined P-gp and strong CYP3A4 inhibitor is given at the same time. Because apixaban is a substrate of both CYP3A4 and P-gp, combining it with an agent that inhibits both P-gp and CYP3A4 strongly can raise apixaban exposure and thereby heighten bleeding risk12. A pharmacokinetic study showed that when apixaban was administered together with ketoconazole (a combined P-gp and strong CYP3A4 inhibitor), apixaban Cmax rose by 62% and AUC rose by 97%3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
Keep taking both medicines exactly as prescribed and do not stop or adjust anything yourself. Your care team can manage this combination safely.
- If you take apixaban 2.5 mg twice daily, your team will typically avoid using it with tucatinib and may choose an alternative.
- If you take a higher dose (5 or 10 mg twice daily), your dose may be reduced by half during treatment with tucatinib.
- Your team may watch you more closely for bleeding.
Tell your pharmacist or prescriber about all your medicines, and report any unusual bruising, nosebleeds, blood in urine or stool, or bleeding that won't stop.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Giving apixaban together with ketoconazole produced a 62% rise in apixaban Cmax and a 97% rise in apixaban AUC relative to apixaban given by itself. In 18 subjects, a 10 mg oral dose of apixaban was given 4 days after starting ketoconazole 400 mg once daily 3.
b) In a drug interaction study, administering apixaban alongside ketoconazole, 400 mg, raised apixaban Cmax and AUC by roughly 1.6-fold and 2-fold, respectively 2.
Common questions
Can I take Apixaban and Tucatinib together?
Tucatinib can raise apixaban levels and increase bleeding risk, so your care team may lower your apixaban dose or avoid the combination. Keep taking both as prescribed and watch for any signs of bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Tucatinib 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 Apixaban and Tucatinib interaction managed?
Keep taking both medicines exactly as prescribed and do not stop or adjust anything yourself. Your care team can manage this combination safely. If you take apixaban 2.5 mg twice daily, your team will typically avoid using it with tucatinib and may choose an alternative. If you take a higher dose (5 or 10 mg twice daily), your dose may be reduced by half during treatment with tucatinib. Your team… 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 Apixaban or Tucatinib 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 (3)
- Product Information: ELIQUIS(R) oral tablets, tablets for suspension, apixaban oral tablets, tablets for suspension. Bristol-Myers Squibb Company (per Manufacturer), Princeton, NJ, 2025. DailyMed
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
- Frost CE, Byon W, Song Y, et al: Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015; 79(5):838-846.
Keep reading about Tucatinib
Keep reading about Apixaban
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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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