Omeprazole and Palbociclib: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Palbociclib
Omeprazole
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. Palbociclib (Ibrance) is a capsule that your body absorbs better in a more acidic stomach. Omeprazole (Prilosec) is a strong acid reducer, and by lowering stomach acid it can cause your body to absorb less of the palbociclib. That means the cancer medicine may not work as well as it should.
This matters because palbociclib is treating your breast cancer, so we want every dose to count. The good news is your care team has options. Please don't stop either medicine on your own. Just talk with your oncologist or pharmacist so they can pick the best acid remedy and make sure your palbociclib stays effective.
Effect: Reduced palbociclib exposure and potentially reduced efficacy (possible decrease in PFS/OS) with PPI coadministration.
Mechanism: Palbociclib capsules exhibit pH-dependent solubility; gastric acid suppression from omeprazole reduces dissolution and absorption. Neither drug is a prodrug requiring activation here.
- Direction: Decreased palbociclib effect.
- Onset: Unspecified.
- Evidence: Probable; clinical significance still being characterized.
- Management: Prefer an H2-antagonist over a PPI in this population. If a PPI is required, use cautiously (especially long term) and consider the palbociclib tablet formulation, which has less pH-dependent absorption. Monitor treatment response.
What happens
Reduced efficacy of palbociclib
Interaction Deep Dive
When palbociclib is given together with proton pump inhibitors (PPIs), progression-free survival and overall survival in patients undergoing treatment for breast cancer may56 or may not72 be reduced. In this patient group, a H2-antagonist should be considered as an alternative to a PPI. Should coadministration be necessary, a PPI should be used with caution, particularly over the long term1, and the tablet formulation of palbociclib should be considered2.
Why it happens (mechanism)
Unknown
How to manage this interaction
What your care team may do:
- Consider switching you from a PPI like omeprazole to an H2-blocker (a different type of acid reducer), which is less likely to interfere.
- If a PPI is still needed, use it carefully, particularly with long-term use.
- Consider the palbociclib tablet form, which is absorbed more reliably when stomach acid is lowered.
- Monitor how well your treatment is working.
What you should do: Keep taking both medicines as prescribed and don't change anything on your own. Tell your oncologist and pharmacist about your omeprazole (including over-the-counter use) so they can choose the best acid option for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a retrospective study of patients with estrogen-positive, HER2-negative metastatic breast cancer (N=112), giving palbociclib together with a proton pump inhibitor (PPI) significantly reduced progression-free survival (PFS) time compared with patients receiving palbociclib alone plus endocrine therapy (14 vs 37.9 months). Palbociclib was taken orally once daily at lunchtime for 21 days, then 7 days without the drug, alongside either fulvestrant or letrozole. The majority of patients received palbociclib 125 mg (61.6%), although dose reductions for toxicity were made to 100 mg (26.8%) and 75 mg (9.8%) when needed. Patients receiving concurrent PPI therapy took either lansoprazole 15 mg (n=42), omeprazole 10 mg (n=11), esomeprazole 20 mg (n=1), or pantoprazole 20 mg (n=2) once daily in the morning with breakfast. A potential mechanism for this interaction is that the rise in gastric pH may have reduced palbociclib plasma concentrations, thereby affecting treatment efficacy. Caution should be exercised particularly during prolonged use of PPIs in this population 1.
b) In drug interaction trials involving healthy subjects, giving a single palbociclib 125 mg tablet together with multiple doses of rabeprazole under overnight fasted conditions had no effect on the pharmacokinetics of palbociclib when compared with the palbociclib tablet given alone 3. Under fasted conditions, giving a single palbociclib 125 mg capsule with multiple doses of rabeprazole reduced palbociclib AUC(inf) and Cmax by 62% and 80%, respectively, compared with the palbociclib capsule alone; under fed conditions, AUC(inf) and Cmax were reduced by 41% and 13% 4.
c) Using palbociclib together with proton pump inhibitors (PPIs) produced a significantly shorter median progression-free survival compared with non-users in 2 retrospective studies of patients with breast cancer (10.6 months vs not reached; dosage form not specified 5; 25.3 months vs 39.8 months; capsule formulation); overall survival (OS) was also significantly shorter in concurrent users compared with non-users in 1 of the studies (1-year OS, 83.1% vs 94%; 2-year OS, 69.5% vs 89.3%; capsule formulation) 6. Patients received endocrine therapy (fulvestrant or aromatase inhibitor) and PPI therapy consisted of dexlansoprazole, esomeprazole, ilaprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole 56.
d) Using palbociclib together with proton pump inhibitors (PPIs) did not significantly affect median progression-free survival compared with non-users in 2 retrospective studies of patients with metastatic breast cancer (14.4 months vs 15.8 months; capsule formulation 7; 20.6 months vs 21 months; tablet formulation 2). Patients received endocrine therapy (fulvestrant or aromatase inhibitor) and PPIs included lansoprazole, pantoprazole, esomeprazole, rabeprazole, and omeprazole 72.
Common questions
Can I take Omeprazole and Palbociclib together?
Omeprazole can lower how much palbociclib your body absorbs, which may make your cancer treatment less effective; ask your oncologist or pharmacist whether an H2-blocker or the tablet form of palbociclib is a better fit, and don't stop anything on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Palbociclib 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 Omeprazole and Palbociclib interaction managed?
What your care team may do: Consider switching you from a PPI like omeprazole to an H2-blocker (a different type of acid reducer), which is less likely to interfere. If a PPI is still needed, use it carefully, particularly with long-term use. Consider the palbociclib tablet form, which is absorbed more reliably when stomach acid is lowered. Monitor how well your treatment is working. What you shou… 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 Omeprazole or Palbociclib 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 (7)
- Del Re M, Omarini C, Diodati L, et al: Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients. ESMO Open 2021; 6(5):100231. PubMed
- Schieber T, Steele S, Collins S, et al: Effect of concurrent proton pump inhibitors with palbociclib tablets for metastatic breast cancer. Clin Breast Cancer 2023; 23(6):658-663. PubMed
- Product Information: IBRANCE(R) oral tablets, palbociclib oral tablets. Pfizer Labs (per FDA), New York, NY, 2022. DailyMed
- Product Information: IBRANCE(R) oral capsules, palbociclib oral capsules. Pfizer Labs (per FDA), New York, NY, 2022. DailyMed
- Caglayan D, Kocak MZ, Geredeli C, et al: The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer. Eur J Clin Pharmacol 2023; 79(2):243-248.
- Lee JE, Kwon SH, Kwon S, et al: Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw Open 2023; 6(7):e2324852. PubMed
- Odabas H, Dogan A, Ozcelik M, et al: Does proton pump inhibitors decrease the efficacy of palbociclib and ribociclib in patients with metastatic breast cancer. Medicina (Kaunas) 2023; 59(3):557-. PubMed
Keep reading about Palbociclib
Keep reading about Omeprazole
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