Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr 1;125(7):1155-1162.
doi: 10.1002/cncr.31917. Epub 2019 Jan 3.

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer

Manvi Sharma  1 , Holly M Holmes  2   3 , Hemalkumar B Mehta  3   4 , Hua Chen  3 , Rajender R Aparasu  3 , Ya-Chen T Shih  5 , Sharon H Giordano  5 , Michael L Johnson  3
Affiliations

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer

Manvi Sharma et al. Cancer. .

Abstract

Background: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer.

Methods: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome.

Results: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation.

Conclusions: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

Keywords: Epidemiology; Medicare Part D; Surveillance; and End Results (SEER)-Medicare; drug-drug interaction; elderly; polypharmacy; predictors; prevalence; proton pump inhibitors; survival; tyrosine kinase inhibitors.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Cohort selection flow diagram
See this image and copyright information in PMC

References

    1. Bartel SB. Safe practices and financial considerations in using oral chemotherapeutic agents. Am J Health Syst Pharm 2007;64: S8–S14. - PubMed
    1. Weingart SN, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ. 2007;334: 407. - PMC - PubMed
    1. Weingart SN, Brown E, Bach PB, et al. NCCN Task Force Report: Oral chemotherapy. J Natl Compr Canc Netw 2008;6 Suppl 3: S1–14. - PubMed
    1. European Society for Medical Oncology. Drug-Drug Interactions Associated with Kinase Inhibitors - Pharmacokinetics, Absorption | OncologyPRO. Available from URL: http://oncologypro.esmo.org/Oncology-in-Practice/Drug-Drug-Interactions-... [accessed 10th May, 2016].
    1. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014;15: e315–326. - PubMed

Publication types

MeSH terms

Substances