Residents and Fellows Research in Progress
Monday, November 13, 2023
01:00 PM–02:30 PM
Abstract
Introduction: Since cancer patients are commonly prescribed multiple concomitant medications, managing DDIs is critical for optimizing efficacy and minimizing toxicity of oral anticancer drugs.
Research Question or Hypothesis: (1) To determine DDI mechanisms for newly approved oral anticancer drugs and (2) to assess the prevalence of potential DDIs in a cohort of adults with solid cancers.
Study Design: Literature review and retrospective review of electronic health records (EHRs).
Methods: DDI mechanisms for 57 oral anticancer drugs, including CDK4/6 inhibitors, PARP inhibitors, PI3K inhibitors, and tyrosine kinase inhibitors, were determined from clinical DDI studies and pharmacokinetic modeling analyses obtained from FDA drug labels and primary literature. Drugs were classified as having a high DDI potential if they were strong or moderate inhibitors, inducers, or sensitive substrates for major cytochrome P450 (CYP) enzymes or drug transporters or if their exposure was reduced by =50% during co-administration with acid reducers. EHRs of 3697 patients seen at an institutional solid tumor board were reviewed to detect potential DDIs, defined as overlapping prescriptions of anticancer drugs with relevant interacting drugs.
Results: Approximately 80% of anticancer drugs had a high DDI potential involving at least one mechanism. The most common DDI mechanisms were CYP3A victims, CYP3A perpetrators, and victims with acid reducers (37.9%, 17.2%, and 13.8% of anticancer drugs, respectively). Approximately one quarter of patients were prescribed at least one of the studied anticancer drugs, among which 17.5 % had =1 potential DDI. The most prescribed anticancer drugs were palbociclib and olaparib, and potential DDIs were identified in 13.5% and 27.0% of patients prescribed these drugs, respectively.
Conclusion: The majority of anticancer drugs had one or more mechanisms of potential DDI, and greater than 1 in 6 patients had at least one potential DDI. These findings demonstrate the importance of identifying and managing DDIs with oral anticancer drugs.
Presenting Author
Fatimah Alhurayri PharmD, MSPurdue University College of Pharmacy
Authors
Theodore Logan MD
Indiana University School of Medicine
Shadia Jalal MD
Indiana University School of Medicine
Nicholas Powell PharmD
Indiana University School of Medicine
Sara Quinney PharmD, PhD
Indiana University School of Medicine
Zeruesenay Desta PhD
Indiana University School of Medicine
James Tisdale PharmD
Purdue University
Islam Younis PhD
Merck & Co.
Tyler Shugg PharmD, PhD
Indiana University School of Medicine
Todd Skaar PhD
Indiana University School of Medicine