Therapeutic Advances in Drug Safety最新文献

To perform optimal monitoring of the safety profile in the postmarketing phase, Marketing Authorization Holders and National Regulatory Authorities (NRAs) must evaluate the adverse drug reactions (ADRs) that occurred and characterize their nature, frequency, and severity. Management is possible through Individual Case Safety Reports (ICSRs), which are the reports of organized and processed data. Globally, the International Council for Harmonisation (ICH) E2B guideline suggests harmonized activities for the ICSR electronic content and transmission. In America, the Pan American Health Organization (PAHO) is the agency responsible to implement cooperation among its members, which are recognized as National Regulatory Authorities of Reference (NRARs) such as Argentina, Brazil, Canada, Chile, Colombia, Cuba, Mexico, and the United States. PAHO published the 'Good Pharmacovigilance Practices for the Americas' suggesting improvement and harmonization in the region. After reviewing the regulatory framework, it is assumed that all NRARs have a regulated ICSR transmission system (i.e. a systematic vigilance system for collecting, analyzing, and disseminating information from ADRs). However, significant differences exist, such as the requirement for social media vigilance, expedited and non-expedited ICSRs, coding, severity, and transmission. The volume of ICSRs has significantly increased, due to using electronic standards managed by the NRAs, which facilitates early identification of new ADRs, allowing the implementation of novel minimization activities, contributing to the continuous assessment of the benefit-risk balance of medicines. Nevertheless, there is still area for improvement, especially in Latin America.

Background: Polypharmacy is a growing phenomenon among elderly individuals. However, there is little information about the frequency of polypharmacy among the elderly population treated in emergency departments (EDs) and its prognostic effect. This study aims to determine the prevalence and short-term prognostic effect of polypharmacy in elderly patients treated in EDs.

Methods: A retrospective analysis of the Emergency Department Elderly in Needs (EDEN) project's cohort was performed. This registry included all elderly patients who attended 52 Spanish EDs for any condition. Mild and severe polypharmacy was defined as the use of 5-9 drugs and ⩾10 drugs, respectively. The assessed outcomes were ED revisits, hospital readmissions, and mortality 30 days after discharge. Crude and adjusted logistic regression analyses, including the patient's comorbidities, were performed.

Results: A total of 25,557 patients were evaluated [mean age: 78 (IQR: 71-84) years]; 10,534 (41.2%) and 5678 (22.2%) patients presented with mild and severe polypharmacy, respectively. In the adjusted analysis, mild polypharmacy and severe polypharmacy were associated with an increase in ED revisits [odds ratio (OR) 1.13 (95% confidence interval (CI): 1.04-1.23) and 1.38 (95% CI: 1.24-1.51)] and hospital readmissions [OR 1.18 (95% CI: 1.04-1.35) and 1.36 (95% CI: 1.16-1.60)], respectively, compared to non-polypharmacy. Mild and severe polypharmacy were not associated with increased 30-day mortality [OR 1.05 (95% CI: 0.89-2.26) and OR 0.89 (95% CI: 0.72-1.12)], respectively.

Conclusion: Polypharmacy was common among the elderly treated in EDs and associated with increased risks of ED revisits and hospital readmissions ⩽30 days but not with an increased risk of 30-day mortality. Patients with polypharmacy had a higher risk of ED revisits and hospital readmissions ⩽30 days after discharge.

Background: Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy.

Objective: To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites.

Design: A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University.

Methods: The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected.

Results: There is no significant correlation between OCTA outcomes and the patient's age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter (r = 0.419, p = 0.005 and r = 0.407, p = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP (r = -0.378, p = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter (r = 0.445, p = 0.003 and r = 0.434, p = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP (r = -0.383, p = 0.011 and r = -0.424, p = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations.

Conclusion: OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes.

Background: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments.

Objectives: This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment.

Design: After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges.

Methods: Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models.

Results: Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child-Pugh-A, Child-Pugh-B, and Child-Pugh-C hepatic impairment, respectively.

Conclusion: The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.