COVID-19 has been announced pandemic by WHO and over 17,000,000 people infected (Till April 21st 2020). The disease is currently under control in China, with a curative rate of 86.8%. Chloroquine (CQ) is an old anti-malarial drug with good tolerability, which had proved to be effective in previous SARS-coronavirus, which spread and disappeared between 2002-2003. In vitro studies demonstrated the efficacy of CQ in curing COVID-19. Consequently, via analytical PBPK modeling, a further preliminary clinical trial has proved the efficacy and safety of CQ in China., and multiple clinical trials were registered and approved to investigate the activity of other analogs of CQ against COVID-19. We have listed all the clinical trials and made a meta-analysis of published data of hydroxychloroquine (HCQ). HCQ could increase the CT improvement and adverse reactions (ADRs) significantly though there was considerable heterogeneity among current researches. Actually, CQ and its analogs have unique pharmacokinetic characteristics, which would induce severe side effects in some circumstances. We have then summarized pharmacological considerations for these drugs so as to provide to the busy clinicians to avoid potential side effects when administered CQ or its analogs to COVID-19 patients, especially in the elderly, pediatrics, and pregnancies.

Objective: The introduction of Bruton’s tyrosine kinase (BTK) inhibitors was a milestone in the treatment of B-cell malignancies in recent years owing to its desired efficacy against chronic lymphocytic leukaemia and small cell lymphocytic lymphoma. However, safety issues have hindered its application in clinical practice. The current study aimed to explore the safety warning signals of BTK inhibitors in a real-world setting using the FDA Adverse Event Reporting System (FAERS) to provide reference for clinical rational drug use.Methods: Owing to the short marketing time of other drugs (zanbrutinib and orelabrutinib), we only analysed ibrutinib and acalabrutinib in this study. All data were obtained from the FAERS database from January 2004 to December 2021. Disproportionality analysis and Bayesian analysis were utilised to detect and assess the adverse event (AE) signals of BTK inhibitors.Results: In total, 43,429 reports of ibrutinib were extracted and 1527 AEs were identified, whereas 1742 reports of acalabrutinib were extracted and 220 AEs were identified by disproportionality analysis and Bayesian analysis. Among reports, males were more prone to develop AEs (58.2% for males vs. 35.6% for females treated with ibrutinib, and 55.9% vs. 31.9%, respectively, for acalabrutinib), and more than 30% of patients that suffered from AEs were over 65 years of age. Subsequently, we investigated the top 20 preferred terms (PTs) associated with the signal strength of ibrutinib and acalabrutinib, and our results identified 25 (13 vs. 12, respectively) novel risk signals. Among the top 20 PTs related to death reports, the terms infectious, pneumonia, pleural effusion, fall, asthenia, diarrhoea, and fatigue were all ranked high for these two BTK inhibitors. Further, cardiac disorders were also an important cause of death with ibrutinib.Conclusion: Patients treated with ibrutinib were more prone to develop AEs than those treated with acalabrutinib. Importantly, infection-related adverse reactions, such as pneumonia and pleural effusion, were the most common risk signals related to high mortality associated with both BTK inhibitors, especially in elderly patients. Moreover, cardiovascular-related adverse reactions, such as atrial fibrillation and cardiac failure, were fatal AEs associated with ibrutinib. Our results provide a rationale for physicians to choose suitable BTK inhibitors for different patients and provide appropriate monitoring to achieve safer therapy and longer survival.

Aims: With the extensive use of tyrosine kinases inhibitors(TKIs) in hepatocellular cancer, cardiac adverse events(AEs) emerged in recent years. This study explored the cardiac AEs of TKIs through the Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. Results: A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib and cabozantinib were identifed. Among them, 17 cardiac AEs signals were detected in regorafenib, 15 cardiac AEs signals were detected in lenvatinib, 57 cardiac AEs signals were detected in sorafenib while 27 cardiac AEs signals were detected in cabozantinib. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR=7.7(3.46,17.17)]. Acute myocardial infarction were detected in lenvatinib [ROR=7.91(5.64,11.09)] and sorafenib[ROR=2.22(1.74, 2.84)]. Acute coronary syndrome were detected in lenvatinib[ROR=11.57(6.84, 19.58)] and sorafenib [ROR=2.81(1.87,4.24)]. Atrial fibrillation were detected in sorafenib [ROR=1.82(1.55,2.14)] and regorafenib [ROR=1.36(1.03,1.81)]. Meanwhile, aortic dissection were detected in sorafenib [ROR=5.08(3.31,7.8)] and regorafenib [ROR=3.39(1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days after TKIs treatment. Patients taking lenvatinib developed acute coronary syndrome increased in the periods of 180 days(64.29%) . Conclusion: Analysis of FAERS provides more precise profile on the characteristics of cardiac AEs after different TKI regimens. Distinct monitoring and appropriate management are needed in the care of the TKIs recipients.