Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review.

OBJECTIVE: The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. METHODS: A search strategy was conducted in MEDLINE, EMBASE, and Google Scholar using a list of predetermined keywords. Peer-reviewed articles written in English and published through June 2021 were included. Articles covered included randomized clinical trials and expert recommendations, as well as patent and other types of reviews. RESULTS: The discussed AEs include weight gain and withdrawal pain, as well as neuromuscular, central nervous system (dysesthesias and peripheral sensory neuropathies, dizziness and ataxia, and dysgeusia), gastrointestinal (nausea, vomiting, and diarrhea), and respiratory symptoms. Additionally, several AEs encountered with entrectinib specifically (cognitive and vision disorders, congestive heart failure, QTc elongation, and skeletal fractures) are discussed. First, an overall mechanism of action explaining these AEs is presented. Then, for each AE, incidence and severity are stated and followed by practical management recommendations. While nearly all AEs were reversible upon TRKi suspension, the proposed managements are mainly constituted of pharmacological and non-pharmacological interventions. CONCLUSION: With the estimated growth of gene sequencing in the coming years, it is foreseeable that TRKi will take a larger position in the oncologic therapeutic arsenal. Therefore, adequate management of AEs associated with TRKi in adults should be a prime focus.

Development of a Web-Based Tool Built From Pharmacy Claims Data to Assess Adherence to Respiratory Medications in Primary Care.

BACKGROUND: Medication adherence in asthma and COPD is notoriously low. To intervene effectively, family physicians need to assess adherence accurately, which is a challenging endeavor. In collaboration family physicians and individuals with asthma or COPD, we aimed to explore the barriers and facilitators of assessing medication adherence in clinical practice (exploratory phase), and to develop a novel web-based tool (e-MEDRESP) that will allow physicians to monitor adherence using pharmacy claims data (development phase). METHODS: We used qualitative research methods and a framework inspired by user-centered design principles. Five focus groups were held: 2 with subjects (n = 15) and 3 with physicians (n = 20), and 10 individual interviews were conducted with physicians. In the exploratory phase, data were analyzed using thematic networks. In the development phase, we identified components to be included in an e-MEDRESP prototype through an iterative approach. The web-based e-MEDRESP tool was constructed by applying algorithms to pharmacy claims data that reflected end-users' recommendations through an informatics approach designed for electronic medical records. RESULTS: The main barriers to assessing medication adherence included a lack of objective information regarding medication use and short duration of medical visits. Physicians emphasized that identifying patients at risk for nonadherence requires a team effort from pharmacists, respiratory therapists, and nurses. Subjects also agreed that the use of easily interpretable pharmacy claims data could be an important facilitator and contributed to the development of the e-MEDRESP prototype, which contains graphical representations of the adherence to respiratory controller medications and dispensing of rescue medications. CONCLUSIONS: The e-MEDRESP tool has the potential to allow physicians to measure adherence objectively and to facilitate patient-physician communication concerning medication use. Future studies are needed to evaluate the feasibility of implementing e-MEDRESP in clinical practice. It would be relevant to develop strategies that could facilitate the sharing of information presented in e-MEDRESP among primary care health professionals.