Cardiac arrhythmias associated with anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) may provoke cardiac arrhythmias. We conducted this pharmacovigilance analysis to research cardiac arrhythmias associated with ALK-TKIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: The first ALK-TKI, named crizotinib, was approved by the Food and Drug Administration (FDA) on 26 August 2011 for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). We evaluated ALK-TKIs-induced cardiac arrhythmias, by using the reporting odds ratio (ROR) and information component (IC) for mining the adverse event report signals in the FAERS database between January 2016 and June 2022. RESULTS: We identified a total of 362 ALK-TKIs-related cardiac arrhythmia reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 (interquartile range [IQR] 7-74) years. Compared with the full database, ALK-TKIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.26, IC025 = 0.26). Crizotinib and alectinib were found to be related to higher reporting of arrhythmias. The median time to onset (TTO) among five ALK-TKI therapies was significantly different (p = 0.044). CONCLUSION: ALK-TKIs present different frequencies of cardiac arrhythmias reporting, with only crizotinib and alectinib producing positive signals in high-level group term (HLGT) level arrhythmia. The time interval between the initial of drug treatment to the onset of arrhythmia varies greatly and cannot be predicted.

Association between potentially inappropriate medication and adverse drug reactions in hospitalized elderly patients.

WHAT IS KNOWN AND OBJECTIVE: The Beers, European Union (EU) and Screening Tool of Older Persons' potentially inappropriate Prescription (STOPP) criteria were developed to improve the safe use of medicines in the elderly. However, the predictive validity of existing criteria to detect adverse drug reactions (ADRs) remains unexplored. The objective of the current study was to determine whether the 2019 Beers, 2015 STOPP or 2015 EU potentially inappropriate medicine (PIM) criteria were associated with ADRs. METHODS: A retrospective, cross-sectional investigation was conducted among older persons (≥60 years of age) admitted to a tertiary hospital in China between April 2019 and December 2019. PIMs were identified as per the Beers, EU and STOPP criteria definitions. ADRs were retrospectively evaluated by two clinical pharmacists using the Naranjo algorithm. Multivariate logistic regression was used to evaluate the factors associated with ADRs in the hospitalized patients. RESULTS AND DISCUSSION: The study participants included 560 hospitalized patients (mean age 72.05 ± 8.15). The prevalence of patients receiving at least one PIM was 52.1%, 37.0% and 42.9% according to the Beers, EU and STOPP criteria, respectively. Univariate analysis showed that ADRs were associated with PIMs listed in the Beers criteria (OR: 2.093, 95% CI: 1.028-4.263, 0.042), but not with the STOPP-listed (OR: 0.536, 95% CI: 0.255-1.123, 0.098) and EU-listed PIMs (OR: 0.258, 95% CI: 0.118-0.563, 0.001). WHAT IS NEW AND CONCLUSION: In contrast to the STOPP and EU criteria on PIMs, the Beers criteria were significantly associated with avoidable ADRs in hospitalized older persons.