Post-marketing Surveillance Research Articles

Biocompatibility and Post-Marketing Surveillance Study of Emollient Plus Medical Device Cream Containing Oligofructans from Ophiopogon japonicus and Acetyl Heptapeptide-4 in Atopic Dermatitis Skin Care

Emollients plus are defined as topical formulations containing active ingredients with no pharmacological effect. They are designed to target multiple mechanisms in AD pathophysiology. The objective of the present study was to assess the efficacy of emollient plus medical device cream by performing a post-marketing surveillance study. It was carried out in cooperation with 88 members of the Polish Association for Atopic Diseases who were diagnosed with AD and voluntarily fulfilled the questionnaire after 14 days of product use. Additionally, the medical device underwent in vitro/ex vivo testing. Cytotoxicity was assessed by in vitro studies: direct MTT assay and indirect Agarose Overlay Assay. An ex vivo EpiDerm™ culture (EPI-200) was used to investigate the irritation potential, and culture medium was collected after 18 h of contact with the skin model to perform a flow cytometric for the analysis of inflammatory cytokines. A dermatological assessment with the local SCORAD was employed to confirm the efficacy of the cream. It was found that 86% of patients with AD observed an improvement in their skin condition during the two-week testing period. In vitro/ex vivo assays confirmed that the product is safe, non-irritant, and does not stimulate the production of proinflammatory cytokines. According to the local SCORAD, the symptoms of AD were alleviated. Moreover, preliminary studies indicated its efficacy in eliminating S. aureus on patients’ skin.

Safety of baricitinib in Japanese patients with rheumatoid arthritis in clinical use: 3-year data of all-case post-marketing surveillance study.

To assess safety of baricitinib in Japanese patients with rheumatoid arthritis in real-world clinical practice. This all-case post-marketing surveillance study included patients initiating baricitinib for rheumatoid arthritis from September 2017 to April 2019. Treatment duration was recorded. Safety data were collected for up to 3 years from baricitinib initiation (up to 4 weeks post discontinuation in discontinuing patients). Safety analyses included 4720 patients; 2580 (54.7%) were ≥65 years old. Baricitinib persistence rate was 45.4% (3 year Kaplan-Meier analysis); the most common discontinuation reason was insufficient effectiveness (n = 1005, 21.3%). Serious adverse events occurred in 600 patients (incidence rate 10.42/100 patient-years; 95% confidence interval, 9.76-11.09). There were 39 deaths (incidence rate 0.43 [0.30-0.57]/100 patient-years). Incidence rate per 100 patient-years for adverse events of special interest were herpes zoster 4.68 (4.22-5.14), serious infection 3.05 (2.68-3.41), malignancy 1.09 (0.87-1.30), major adverse cardiovascular events 0.35 (0.23-0.48) and venous thromboembolism 0.25 (0.15-0.36). Incidence rates did not increase with prolonged exposure. No new safety concerns were identified during this 3 year post-marketing surveillance study of baricitinib in Japanese patients with rheumatoid arthritis. Patients and clinicians should be cognizant of herpes zoster and other serious infection risks during baricitinib treatment, especially in the first 6 months.

Sildenafil-induced priapism in a dog : an unusual case report

BackgroundPriapism is defined as erection that lasts for more than 4 h without sexual stimulation. There are various causes of priapism, but there are no reports of sildenafil-induced priapism in dogs. In human medicine, there were no pre-marketing reports of priapism caused by sildenafil, but post-marketing surveillance has shown that it is rare. In cases of pulmonary hypertension in dogs, sildenafil is the first-line drug of choice for symptomatic relief.Case presentationAn 11-year-old neutered male Maltese dog that presented with tachypnea and cough was diagnosed with myxomatous mitral valve disease, American College of Veterinary Internal Medicine (ACVIM) stage C, and was treated medically. Eighteen months after the diagnosis, severe pulmonary hypertension occurred due to left heart disease. At 20 months postdiagnosis, pleural effusion occurred, and sildenafil (2 mg/kg twice daily) was added to the existing treatment. Two weeks later, the dyspnea recurred, confirming pleural fluid recurrence, and sildenafil was increased to 2 mg/kg thrice daily. One day later, the patient developed persistent erections and penile pain. Penile amputation and urethrostomy were recommended but were refused; therefore, analgesia and palliative care were provided. The patient died of acute dyspnea 22 months after the first presentation, with no specific priapism recurrence at the time of death.ConclusionTo the best of our knowledge, this is the first report of sildenafil-induced priapism in a dog with pulmonary hypertension.

Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

Safety evaluation of the trastuzumab biosimilar in Iranian women with HER2-positive breast cancer undergoing adjuvant chemotherapy: a post-marketing surveillance

ABSTRACT Background Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). Research Design and Methods The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. Results A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. Conclusions The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. Clinical Trial Registration www.clinicaltrials.gov identifier is NCT06021379.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Safety and Effectiveness of Four-Factor Prothrombin Complex Concentrate in Special Populations with INR Below 2: A Post-Marketing Surveillance Study.

We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitaminK antagonist (VKA) reversal in Japanese patients. This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0. Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0years vs 74.0years), body mass index (22.1kg/m2 vs 21.9kg/m2), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5IU/kg [INR < 2.0 group] and 29.2IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (- 28%) and 1.31 (- 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups. This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date.

Predictors of continuation for asenapine from real-world data in patients with schizophrenia

BackgroundThe continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties.MethodsOur investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure.ResultsMultivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%.ConclusionsOur findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.

Post-marketing safety surveillance of fostamatinib: an observational, pharmacovigilance study leveraging FAERS database

ABSTRACT Objective Fostamatinib, an FDA-approved oral small-molecule spleen tyrosine kinase (SYK) inhibitor, is used to treat thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have not responded to previous treatments. However, comprehensive safety data is lacking. This study uses the FDA Adverse Event Reporting System (FAERS) database to explore real-world adverse events (AEs) related to fostamatinib, aiming to inform its clinical use. Methods The FAERS database was retrospectively queried to extract reports associated with fostamatinib from 2019 to 2023. To identify and evaluate potential AEs in patients receiving fostamatinib, various disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed. Results A total of 23 AE signals were included in our analysis. Among them, hypertension, blood pressure increase, blood pressure abnormality, hepatic enzyme increase, and diarrhea were consistent with the common AEs described for fostamatinib in clinical trials. In addition, unexpected serious AEs were detected including cerebral thrombosis and necrotizing soft tissue infection. The median time to onset of fostamatinib-related AEs was 86 days. Conclusion Our investigation revealed several possibly emergent safety concerns associated with fostamatinib in real-world clinical practice, which might provide essential vigilance evidence for clinicians and pharmacists to manage the safety issues of fostamatinib.

Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System.

Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an increasingly prevalent class of drugs for managing overweight/obesity and type 2 diabetes mellitus. Postmarket surveillance is essential for characterizing their risk profiles in real-world patient populations as clinical use increases. This study investigated the association of GLP-1RAs with mortality and serious adverse events (AEs) reported to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods A disproportionality analysis was conducted utilizing FAERS data from Q2 2005 to Q1 2024 to identify AEs listing an approved GLP-1RA as the primary suspect drug. The reporting odds ratio (ROR) was calculated for mortality and serious AEs associated with each GLP-1RA compared to the combined group of all other GLP-1RAs. A signal of disproportionate reporting indicating a potential safety concern was defined as a lower bound of the 95% CI for the ROR exceeding 1.0. Results The analysis identified 287,201 AEs associated with GLP-1RAs during the study period. Disproportionality analyses revealed statistically significant elevated signals for mortality with the earliest approved GLP-1RAs: Byetta (ROR = 2.20, 95% CI: 2.06-2.34) and Victoza (ROR = 2.12, 95% CI: 1.98-2.28). Significant elevated signals for serious AEs were identified with the semaglutide products Ozempic (ROR = 2.77, 95% CI: 2.69-2.85), Rybelsus (ROR = 2.42, 95% CI: 2.26-2.60), and Wegovy (ROR = 1.30, 95% CI: 1.22-1.39); the liraglutide products Victoza (ROR = 2.10, 95% CI: 2.04-2.15) and Saxenda (ROR = 2.21, 95% CI: 2.09-2.33); and Byetta (ROR = 1.11, 95% CI: 1.08-1.14) compared to other GLP-1RAs. The newer GLP-1RAs were associated with a higher proportion of serious AEs reported in younger patients (p < 0.001) and females (p < 0.001). Conclusion This pharmacovigilance study utilizing the FAERS database identified potential safety signals of increased mortality and serious AE reporting associated with certain GLP-1RAs, particularly the earlier approved liraglutide agents Byetta and Victoza. These findings highlight the importance of proactive postmarket surveillance to characterize the real-world safety profiles of individual GLP-1RA drugs.

Insight into Quantum Computing and Deep Learning Approach for Drug Design

: In recent years, substantial modelling breakthroughs have been achieved in artificial intelligence due to new algorithms, improved computer power, and expanded storage capacity. These factors have made it possible to process large amounts of data in a short amount of time. By using quantum computing in conjunction with deep learning models, it has been possible to explain the characteristics of ligands and their interactions with biological targets. This contributes to the process of ligand identification and ultimately results in the optimization of drug design. This review explains the extensive use of quantum deep learning in the development of drug design from traditional to quantum-powered deep learning neural networks that cover some domains like variational quantum Eigen solver, variational quantum circuits, quantum convolutional deep neural networks, QC-based deep neural networks for QSAR, as well as quantized generative models for the discovery of small drug molecules. Quantum computing can execute incredible computational work tenfold faster than current technology, transforming drug design, development, and post-marketing surveillance. This will reduce the time and resources needed to develop a medicine. Scientific research is moving toward quantum computing since it is anticipated that QC-based deep learning technologies can predict and mimic the characteristics, structures, and activities of molecules more efficiently than different ML techniques or conventional computers.

Pharmaceutical Market Access in Latin America: Analyzing Approval Requirements in Three Key Nations: Ecuador, Dominican Republic and Nicaragua

: This article presents a comprehensive and comparative analysis of the regulatory frameworks governing the approval of pharmaceuticals in the Dominican Republic, Ecuador, and Nicaragua. It delves into the intricate scientific terminology and complex procedures inher-ent in these regulatory systems, shedding light on the demanding requirements that pharmaceu-tical companies must fulfil to secure market access in these countries. Employing a comparative approach, the article explores both the analogy and differences in the approval processes, focus-ing on factors such as safety standards, efficacy assessments, clinical trial prerequisites, post-marketing surveillance, and overall transparency. The findings contribute to a deeper under-standing of the scientific accuracy and ongoing efforts towards regulatory harmonisation within the pharmaceutical industry across these countries. Furthermore, this study aims to define the regulatory requirements for drug approval in the LATAM region, explicitly emphasising the Dominican Republic, Ecuador, and Nicaragua. It provides insights into the current pharmaceuti-cal market landscape in Latin America, compares the regulatory requirements for drug approval in these three countries, and offers guidance on preparing dossiers for obtaining authorisation of pharmaceutical drug products. By examining the similarities and differences in regulatory stand-ards, this article facilitates a comprehensive understanding of the stringency ratios between these countries and assists companies in navigating the specific regulatory landscapes to achieve suc-cessful drug approvals

Identification of Novel Signals Associated with US-FDA Approved Drugs (2013) Using Disproportionality Analysis.

Drugs are related with various adverse drug reactions (ADRs), however, many unexpected ADRs of drugs are reported through post-marketing surveillance. The current study's goal is to uncover potential signals connected with FDA-approved medications in the United States (2013). Open Vigil 2.1-MedDRA-v24 (data 20004Q1-2021Q3) was used as a tool to query the FAERS data. To find possible signals, disproportionality measures such as Proportional Reporting Ratio (PRR 2) with associated Chi-square value, Reporting Odds Ratio (ROR 2) with 95% confidence interval, and case count (3) were calculated. A total of eight potential signals were identified with five drugs. Positive signals were found with pomalidomide, canagliflozin, dolutegravir sodium, macitentan and ibrutinib. However, further causality assessment is required to confirm the association of these drugs with identified potential signals.

A Comprehensive Analysis of Class I Medical Device Recalls: Unveiling Patterns, Causes and Global Impacts.

In the landscape of medical device regulation, Class I recalls serve as pivotal indicators of potential risks, necessitating comprehensive analysis to unveil underlying patterns and causal factors. This research offers a detailed examination of Class 1 recalls, focusing on the critical aspects of device classification, review panel involvement, and the geographic distribution of recalling companies. Utilizing a robust dataset spanning multiple jurisdictions and device categories, this study reveals recurring trends in recall occurrences, providing insights into the regulatory mechanisms governing device safety assessments. Furthermore, it investigates the role of review panels in evaluating device safety and effectiveness, shedding light on their significance in the recall process. Moreover, the analysis explores the countries of origin of companies initiating recalls, offering insights into the global impact of regulatory actions on medical device manufacturers. By understanding the drivers behind recall decisions and their implications on a regional scale, regulatory authorities, and healthcare stakeholders can implement targeted measures to enhance patient safety and strengthen post-market surveillance practices.

Field Study on the Assessment of Antimalarial Drug Quality Using Minilab Kitin India

Background: A lack of proper anti-malarial medication use can lead to drug resistance, failed therapy, and even death. It is unclear how widespread the use of fake anti-malarial medications is in India. Better malaria treatment and the execution of regulatory initiatives to improve anti-malarial drug quality necessitate regional research into the quality of available anti-malarial pharmaceuticals. This study aimed to look into the quality of anti-malarial drugs in regions of India where malaria is common. Conclusions about the prevalence of substandard anti-malarial medications in Indian communities can be drawn from the findings. Methods: Samples of anti-malarial pills were bought from stores in five different Indian areas. One hundred and fifty anti-malarial drug samples were gathered. Using a GPHF minilab lab kit, the quality of the following samples was determined: chloroquine (n=50), artemether lumefantrine (n=50), artesunate sulphadoxine-pyrimethamine (n=14), and primaquine (n=31). Results: This research confirmed that 98% of the tablets disintegrated properly in a minilab disintegration test. As a result, when compared to both the full set of standards and 80% of the samples, 99% of the samples passed the preliminary qualitative TLC test. Only 4% of samples (those with insufficient amounts of the active medicinal component) failed the quantitative HPLC test. Conclusion: Anti-malarial medicine counterfeiting has been found to be quite uncommon in India compared to other countries. However, further research is needed, such as post-marketing surveillance, to ensure that effective anti-malarials are distributed to the public.

Evidence for differences in patterns of temporal trends in meta-analyses of diagnostic accuracy studies in the Cochrane database of systematic reviews

ObjectivesTemporal trends in comparative meta-analyses of interventions are well-recognized in the medical literature. For studies of diagnostic test accuracy (DTA), evidence of temporal trends is growing and the importance of assessing and reporting them has been highlighted in recent guidelines on postmarket surveillance in several jurisdictions. In this study, we evaluate the prevalence and patterns of time trends using a larger and more up-to-date set of DTA systematic reviews than has previously been examined, from the Cochrane Database of Systematic Reviews. Study Design and SettingCumulative meta-analysis was conducted on bivariate random effects meta-analysis estimates of sensitivity and specificity, after ranking studies by publication date. Trends for all studies were assessed graphically using plots of summary estimates by study rank, and using receiver operating characteristic plots of sensitivity vs specificity. Linear trends were also described using weighted linear regression with autocorrelated errors of summary estimates against study rank. Various patterns of nonlinear trends were characterized descriptively. ResultsThe analysis included 46 reviews (92 meta-analyses) conducted between 2017 and 2022. The total number of studies within all reviews was 1486, with a median (IQR) 7134 (2782–16,406) participants per review. Reviews had a median (IQR) time span of 19 (15-25) publication years. Time trends in at least 1 DTA measure were observed in 40 (87%) reviews, and statistically significant linear trends in 32 (70%) reviews. Nonlinear time trends were observed in 14 (30%) reviews. There was no evidence for a trend in either DTA measure in 6 (13%) reviews. ConclusionThe study contributes evidence on the variety in patterns of linear and nonlinear temporal DTA trends which has not previously been described. We recommended researchers check statistical assumptions of trend analysis methods, eg, using graphical methods. Further research into potential reasons for time trends could contribute to the robustness of future meta-analyses.

Real-world safety and effectiveness of intravenous fomepizole in patients with ethylene glycol and methanol poisoning in Japan: results of a 7-year post-marketing surveillance study

ABSTRACT Background Fomepizole is a competitive alcohol dehydrogenase inhibitor used for the treatment of ethylene glycol and methanol poisoning. We evaluated the safety and effectiveness of fomepizole in patients with ethylene glycol or methanol poisoning in Japan. Research design and methods This retrospective post-marketing surveillance study conducted in Japan registered patients who received fomepizole intravenous infusion per the package insert (January 2015−June 2022). Endpoints included adverse drug reactions/infections (ADRs), arterial blood pH, and treatment outcomes. Results Of 147 patients registered (91 institutions), 131 and 126 were included in the safety and effectiveness analysis sets, respectively. Mean age was 43.6 years, and 66.4% were male. Mean time from poison ingestion to treatment was 15.1 hours; 66.4% received concomitant hemodialysis. No serious ADRs were reported. ADRs were reported in seven patients; the most-reported ADR was vomiting (2.3%). Seven patients died, 105 survived without sequelae, and 19 survived with sequelae. Most common sequelae were renal failure or renal dysfunction. Mean arterial blood pH increased to 7.4 by 4 hours of treatment, remaining stable for 24 hours post-treatment. Conclusions Fomepizole is well tolerated and helps improve clinical outcomes in patients with ethylene glycol or methanol poisoning in Japan. Trial registration Japanese Pharmaceutical Information Center (JapicCTI-152817).

Recent approaches of regulatory perspectives for the registration of drugs in southern states in India

Recent approaches in regulatory perspectives for the registration of drugs in Southern states of India have been characterized by a focus on enhancing efficiency, transparency, and safety in the drug approval process. This involves the adoption of stringent regulatory frameworks aligned with international standards to ensure the quality, efficacy, and safety of pharmaceutical products. One significant development is the implementation of electronic submission systems for the registration of drugs, streamlining the application process and reducing administrative burdens for regulators and pharmaceutical companies. Additionally, there has been an emphasis on strengthening post-marketing surveillance mechanisms to monitor the safety and efficacy of drugs once they are in the market, enabling prompt identification and mitigation of potential risks or adverse reactions. Collaborative efforts between regulatory authorities, industry stakeholders, and healthcare professionals have also been encouraged to facilitate knowledge exchange and capacity building in regulatory compliance and pharmacovigilance. Overall, these recent approaches reflect a concerted effort to uphold public health standards and ensure access to safe and effective medications for the population of Southern states in India.

Real-World Safety Profile of Biologic Drugs for Severe Uncontrolled Asthma: A Descriptive Analysis from the Spanish Pharmacovigilance Database.

Background: The present investigation provides a thorough analysis of adverse drug reactions (ADRs) reported in the Database of the Spanish Pharmacovigilance System (FEDRA) for biologic medications primarily indicated for severe refractory asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Our main objective was to identify ADRs not documented in the drugs' Technical Sheets (summary of product characteristics, SmPC), potentially indicating unrecognized risks meriting pharmacovigilance attention. Methods: Data spanning from each drug's market introduction until 22 January 2024, were analyzed, sourced from direct submissions to the Spanish Pharmacovigilance System, industry communications, and literature reviews. We evaluated notifications impartially to ensure a comprehensive review of all the ADRs associated with these medications. Results: This investigation underlines the critical role of post-marketing surveillance in enhancing patient safety. It emphasizes the necessity for healthcare professionals to report ADRs comprehensively to foster a robust pharmacovigilance system. Furthermore, the study highlights gaps between the reported ADRs and the information provided in SmPCs, signaling potential areas for improvement in drug safety monitoring and regulatory oversight. Conclusions: Finally, these findings may contribute to informed decision making in clinical practice and regulatory policy, ultimately advancing patient care and safety in the management of severe uncontrolled asthma.

Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance.

Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021. Among 570 patients who participated, 523 (91.75%) were female and the mean±standard deviation (SD) age was 52.4±14.1years. At baseline, NMOSD expanded disability status scale mean±SD was 4.19±2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean±SD glucocorticoid dose reduced from 12.28±10.17mg/day at the index date to 8.11±7.30mg/day at 6months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6months. In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period. UMIN Clinical Trials Registry, UMIN000041047.