Authors: Orogun, Lisajo | Chyou, Te-yuan | Nishtala, Prasad S.
Article Type: Research Article
Abstract: BACKGROUND: Recently, antivirals, including remdesivir, have been repurposed to treat COVID-19 infections. Initial concerns have been raised about the adverse renal and cardiac events associated with remdesivir. OBJECTIVE: This study aimed to analyse the adverse renal and cardiac events associated with remdesivir in patients with COVID-19 infections using the US FDA adverse event reporting system. METHOD: A case/non-case method was used to determine adverse drug events associated with remdesivir as the primary suspect drug between January 1, 2020, and November 11, 2021, for patients with COVID-19 infections. Cases were reports for remdesivir with ≥1 ADEs as preferred terms included in …the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes ‘Renal and urinary disorders’ or ‘cardiac’ disorders. To measure disproportionality in reporting of ADEs, frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, and EBGM > 1 for ADEs with ≥4 reports. Sensitivity analyses were undertaken by excluding reports for non-Covid indications and medications strongly associated with AKI and cardiac arrhythmias. RESULTS: In the main analysis for remdesivir use in patients with COVID-19 infections, we identified 315 adverse cardiac events comprising 31 different MeDRA PTs and 844 adverse renal events comprising 13 different MeDRA PTs. Regarding adverse renal events, disproportionality signals were noted for “renal failure” (ROR = 2.8 (2.03–3.86); EBGM = 1.92 (1.58–2.31), “acute kidney injury” (ROR = 16.11 (12.52–20.73); EBGM = 2.81 (2.57–3.07), “renal impairment” (ROR = 3.45 (2.68–4.45); EBGM = 2.02 (1.74–2.33). Regarding adverse cardiac events, strong disproportionality signals were noted for “electrocardiogram QT prolonged” (ROR = 6.45 (2.54–16.36); EBGM = 2.04 (1.65–2.51), “pulseless electrical activity” (ROR = 43.57 (13.64–139.20); EBGM = 2.44 (1.74–3.33), “sinus bradycardia” (ROR = 35.86 (11.16–115.26); EBGM = 2.82 (2.23–3.53), “ventricular tachycardia” (ROR = 8.73 (3.55–21.45); EBGM = 2.52 (1.89–3.31). The risk of AKI and cardiac arrythmias were confirmed by sensitivity analyses. CONCLUSION: This hypothesis-generating study identified AKI and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections. The relationship between AKI and cardiac arrhythmias should be further investigated using registries or large clinical data to assess the impact of age, genetics, comorbidity, and the severity of Covid infections as potential confounders. Show more
Keywords: Antivirals, patient safety, pharmacovigilance, pharmacoepidemiology, elderly, Bayesian
DOI: 10.3233/JRS-220009
Citation: International Journal of Risk & Safety in Medicine, vol. 34, no. 2, pp. 87-99, 2023
Authors: Nicholls, Connie | Chyou, Te-yuan | Nishtala, Prasad S
Article Type: Research Article
Abstract: BACKGROUND: Antimuscarinics are the backbone of the pharmacological management of overactive bladder. Still, concerns have been raised over the nervous system (NS) adverse drug events (AEs) due to their dissimilarities to muscarinic receptor-subtype affinities. OBJECTIVE: This study aimed to identify the nervous system and gastrointestinal adverse drug events (ADEs) associated with solifenacin use in older adults (≥65 years). METHODS: A case/non-case analysis was performed on the reports submitted to the FDA Adverse Event Reporting System (FAERS) between 01/01/2004 and 30/06/2020. Cases were reports for solifenacin with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) …system organ classes ‘nervous system’ or ‘gastrointestinal’ disorders. Non-cases were all other remaining reports for solifenacin. The case/non-cases was compared between solifenacin and other bladder antimuscarinics. Frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to measure disproportionality. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1, for ADEs with ≥4 reports. RESULTS: 107 MedDRA preferred terms (PTs) comprising 970 ADE reports were retrieved for nervous system disorders associated with solifenacin. For gastrointestinal disorders, 129 MedDRA PTs comprising 1817 ADE reports were retrieved. Statistically significant results were found for ‘altered state of consciousness’: ROR = 9.71 (2.13–44.35), PRR = 9.69 (2.12–44.2) and IC = 1.29 (0.93–1.66). CONCLUSIONS: The disproportionality reporting of ‘altered state of consciousness ’, a previously unidentified ADE, was unexpected. Further monitoring of this ADE is needed to ensure patient safety, as this could be linked to poor balance and falls in older adults. Show more
Keywords: Antimuscarinics, patient safety, pharmacovigilance, pharmacoepidemiology, elderly, reporting odds ratio
DOI: 10.3233/JRS-210054
Citation: International Journal of Risk & Safety in Medicine, vol. 34, no. 1, pp. 63-73, 2023