Pantoprazole with Capecitabine Interaction Details
Brand Names Associated with Pantoprazole
- Pantoprazole
- Protonix®
Brand Names Associated with Capecitabine
- Capecitabine
- Xeloda®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 22, 2023
Interaction Effect
Reduction in capecitabine efficacy
Interaction Summary
Coadministration of capecitabine with a proton pump inhibitor (PPI) may lower the antitumor efficacy of capecitabine based on an ad hoc evaluation of a capecitabine efficacy trial and reduced recurrence-free survival in a retrospective review of patients with early stage colorectal cancer . Data from a pharmacokinetic study of coadministration of esomeprazole and capecitabine suggest the proposed interaction is not due to altered pharmacokinetics of capecitabine; further studies are warranted to validate the drug interaction and clarify a mechanism . Consider discontinuing the PPI or adjusting oral capecitabine to parenteral fluorouracil regimens to avoid this interaction .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Coadministration of capecitabine with a proton pump inhibitor (PPI) may lower the antitumor efficacy of capecitabine. Consider discontinuing the PPI or adjust oral capecitabine to parenteral fluorouracil regimens to avoid this interaction .
Mechanism Of Interaction
Unknown
Literature Reports
A) Coadministration of capecitabine with a proton pump inhibitor (PPI) significantly reduced capecitabine efficacy in an ad hoc analysis of the TRIO-013/LOGiC trial in patients with metastatic esophagogastric cancer randomized to capecitabine/oxaliplatin with or without lapatinib (N=545). PPI use was identified by medication records, with 20% or more overlap for the duration of study treatment, and was evenly distributed across treatment arms. Among patients treated with capecitabine/oxaliplatin (n=117), those without a concurrent PPI had a significantly prolonged median progression-free survival (PFS, 5.7 vs 4.2 months) and median overall survival (OS, 11.3 vs 9.2 months) compared with PPI-treated patients; patients treated with lapatinib did not have a difference in PFS or OS between concurrent PPI or not. Neither pharmacokinetics nor drug levels were assessed during the original trial .
B) Coadministration of capecitabine monotherapy with a proton pump inhibitor (PPI) at any point was associated with an increased recurrence risk in a retrospective review of patients with early stage colorectal cancer (N=298). Patients who took a concurrent PPI while on capecitabine treatment (n=77) had a significant decrease in 5-year recurrence-free survival (RFS) rate compared with patients who did not take a PPI (n=221; 74% vs 83%), but overall survival was not effected. RFS was not different between the 2 groups when adjusting for male gender, stage III, advanced age, and poorer Eastern Cooperative Oncology Group performance status. Neither pharmacokinetics nor drug levels were assessed during capecitabine treatment in the patients included in this review.
C) In a randomized crossover trial, patients with solid tumors (n=22) were assigned to 2 sequence groups, each with 3 phases: esomeprazole administered 3 hours before capecitabine, capecitabine administered alone, and capecitabine administered concomitantly with cola with esomeprazole administered 3 hours before capecitabine. After esomeprazole administration, there was a nonsignificant increase of 18.9% (95% CI, -10% to 57%) in capecitabine AUC(0 to infinity) and 9.9% (95% CI, -33% to 80.1%) in Cmax compared to capecitabine alone. Capecitabine half-life was significantly longer after esomeprazole administration (0.63 vs 0.46 hours). Concomitant cola use with capecitabine did not significantly reverse the AUC effects observed after esomeprazole (relative difference, 3.3%; 95% CI, -16.3% to 27.4%). Data suggest the proposed interaction between capecitabine and esomeprazole cannot be explained by pharmacokinetics. Results from this study show capecitabine exposure is not influenced by esomeprazole coadministration and contradicts theories that proton pump inhibitors (PPIs) reduce capecitabine absorption and effect. Additional prospective studies are warranted to confirm a drug-drug interaction and to elucidate a mechanism .
Pantoprazole Overview
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Pantoprazole is used to treat damage from gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 5 years of age and older. Pantoprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults with GERD. It is also used to treat conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome in adults. Pantoprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount of acid made in the stomach.
Capecitabine Overview
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Capecitabine is used in combination with other medications to treat breast cancer that has come back after treatment with other medications. It is also used alone to treat breast cancer that has not improved after treatment with other medications. Capecitabine is also used to treat colon or rectal cancer (cancer that begins in the large intestine) that has gotten worse or spread to other parts of the body. It is also used to prevent colon cancer from spreading in people who have had surgery to remove the tumor. Capecitabine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.