Retrospective evaluation of erlotinib and gefitinib used in the military health system from the perspective of drug-drug interactions.

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e15108 Background: Erlotinib and gefitinib are epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) approved primarily for non-small cell lung cancer treatment, with pharmaceutical drug-drug interactions (DDIs) that are vague and poorly understood. Previous studies show that concomitant use of EGFR-TKIs with fluoxetine or losartan results in inhibition of both fluoxetine and losartan. Since DDIs can cause significant clinical ramifications, drugs that may interact with erlotinib or gefitinib must be identified. Methods: Data review was performed by Military Health System (MHS) data experts with data provided by the Joint Pathology Center (JPC) from the Department of Defense (DoD) Cancer Registry, the comprehensive ambulatory/professional encounter record (CAPER) and the pharmacy data transaction service (PDTS). Patients treated for cancer were identified, and the CAPER database was used to identify comorbidities. The PDTS database identified prescription drugs filled during erlotinib/gefitinib use, for all cancers. Patients were sorted into subgroups, (1) completed treatment (erlotinib or gefitinib was the last drug that patients completed, without recorded side effects), or (2) discontinued treatment (patients were treated with erlotinib or gefitinib but had recorded side effects and/or switched treatment). PDTS data and retrospective analysis of encounter notes, were used to sort medications into those that were taken before or after (“.”, “,”, “/”, or space between drugs) and those that were taken at the same time (“+”, “-/+”, or “and” between drugs). Results: 348 patients had diagnosis data, with 234 patients having completed treatment and 114 patients having discontinued treatment. Patients who discontinued treatment were diagnosed with more health issues than patients who completed treatment. A total of 258 patients had pharmacy data filled for erlotinib (240 patients) or gefitinib (18 patients). Of these, 177 patients completed treatment and 81 patients discontinued treatment. Patients in the completed treatment group filled 1 to 75 drugs, median range 11-20 drugs. Patients in the discontinued treatment group filled 3 to 103 drugs, median range 31-40 drugs. Patients who discontinued treatment filled more drugs than patients who completed treatment. The 20 most filled drugs, associated with side effects during erlotinib or gefitinib usage and the specific associated side effects were identified. Conclusions: This review cannot conclude that any drug resulted in erlotinib or gefitinib discontinuation. However, associations between top filled drugs and side effects have been made. Proof of concept in vitro laboratory testing should be done with these identified drugs, to confirm mechanistic interactions that may lead to clinical effects.