Spontaneous Reports Research Articles

Comparison of vaccine-induced immune thrombocytopenia and thrombosis cases following two adenovirus-vectored COVID-19 vaccines

Background:Vaccine-induced immune thrombocytopenia and thrombosis (VITT) was first described after administration of adenovirus-vectored COVID-19 vaccines including Ad26.COV2.S and ChAdOx1 nCoV-19. It is not known if the clinical characteristics and outcomes of VITT after Ad26.COV2.S and ChAdOx1 nCoV-19 vaccination are different. We assessed demographic and clinical characteristics, laboratory findings and outcomes in patients with VITT after each vaccine.Methods:Spontaneous postmarketing reports of VITT after Ad26.COV2.S were identified from Janssen’s Global Safety Database and classified using NICE criteria (n = 86). Cases after ChAdOx1 nCoV-19 were identified from a published case series (n = 220). The analysis is descriptive.Results:The median age of patients with definite/probable VITT after Ad26.COV2.S or ChAdOx1 nCoV-19 vaccination is 43 and 48 years, respectively. Median time-to-onset is 11 days and 14 days post-vaccination, cerebral venous thrombosis (CVT) is present in 50.6% and 50%, and mortality is 30% and 22% of patients, respectively. Women make up 55.3% of cases after Ad26.COV2.S and 55% after ChAdOx1 nCoV-19, 74%/60% of CVT cases and 68%/62.5% of deaths. Patients present with severe thrombocytopenia, grossly elevated D-dimer, and most test positive for anti-platelet factor-4 antibodies. Patients with preexisting rare autoimmune diseases are observed despite the small sample sizes.Conclusion:Within the limitations of the data, our study finds no strong evidence for a clinically relevant difference in VITT occurring after Ad26.COV2.S or ChAdOx1 nCoV-19. Observed differences in some parameters likely result from the demographic of the populations vaccinated, and the situational and reporting differences in how, when, and where patients were identified and treated.

A disproportionality analysis of interstitial lung disease associated with drug therapy in spontaneous adverse event reports

ABSTRACT Background Interstitial lung disease (ILD) is a group of disorders characterized by inflammation and fibrosis of lung tissue that make it hard to carry oxygen. Our study aimed to comprehensively evaluate the risk of drug-induced ILD using data from the FDA Adverse Event Reporting System (FAERS) database. Research design and methods We queried the ILD reports from 2004 to 2023. The reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were calculated to detect disproportionality signals for drugs associated with ILD. Results A total of 39,332 ILD-related reports were identified. The most frequently reported drugs were Methotrexate (N = 1245), followed by Pembrolizumab (N = 1026), Amiodarone (N = 975), Rituximab (N = 915), and Doxorubicin (N = 911). Disproportionality analysis revealed significant signals for the top 50 drugs, including Trastuzumab deruxtecan (ROR 56.25, 95% CI 51.27–61.72; IC025 5.49), Ramucirumab (ROR 27.80, 95% CI 241.6–31.99; IC025 4.50), Amiodarone (ROR 24.35, 95% CI 22.82–25.99; IC025 4.40), Gefitinib (ROR 23.02, 95% CI 20.66–25.66; IC025 4.29), and Doxorubicin (ROR 13.99, 95% CI 13.09–14.95; IC025 3.64). Conclusions Drug-induced ILD represents a significant challenge in clinical practice. Our findings underscore the importance of maintaining a high index of suspicion for drug-induced ILD, particularly when prescribing medications identified as having significant associations with ILD.

Interplay of Spontaneous Reporting and Longitudinal Healthcare Databases for Signal Management: Position Statement from the Real-World Evidence and Big Data Special Interest Group of the International Society of Pharmacovigilance.

Signal management, defined as the set of activities from signal detection to recommendations for action, is conducted using different data sources and leveraging data from spontaneous reporting databases (SRDs), which represent the cornerstone of pharmacovigilance. However, the exponentially increasing generation and availability of real-world data collected in longitudinal healthcare databases (LHDs), along with the rapid evolution of artificial intelligence-based algorithms and other advanced analytical methods, offers a wide range of opportunities to complement SRDs throughout all stages of signal management, especially signal detection. Integrating information derived from SRDs and LHDs may reduce their respective limitations, thus potentially enhancing post-marketing surveillance. The aim of this position statement is to critically evaluate the complementary role of SRDs and LHDs in signal management, exploring the potential benefits and challenges in integrating information coming from these two data sources. Furthermore, we presented successful cases of the interplay between SRDs and LHDs for signal management, along with future opportunities and directions to improve such interplay.

Improving the Pharmacovigilance System in Medical Organisations as an Opportunity to Enhance the Quality of Pharmacotherapy

INTRODUCTION. It is essential to monitor the efficacy and safety of medicinal products as part of post-marketing surveillance to identify, assess, and prevent adverse drug reactions (ADRs). The effectiveness of pharmacovigilance depends largely on healthcare professionals’ adherence to the requirements and timeframes for reporting information to regulatory authorities.AIM. This study aimed to identify and systematise the key aspects of pharmacovigilance through an analysis of experience in organising pharmacovigilance in Moscow-based healthcare institutions in 2018–2024 to determine the focus areas for implementing, monitoring, and improving the pharmacovigilance system operating in medical organisations.DISCUSSION. The significance of pharmacovigilance systems and the need for their continuous improvement are underpinned by experience in establishing pharmacovigilance databases, including the global VigiBase database, the European Union’s EudraVigilance database, and the Eurasian Economic Union’s database. The main pharmacovigilance tools include active surveillance and collection of unsolicited/solicited reports of suspected ADRs. The Russian Federal Service for Surveillance in Healthcare (Roszdravnadzor) has developed clear operational criteria for pharmacovigilance in medical organisations. These criteria require that medical organisations should have in-house regulations for collecting, registering, and reporting data on ADRs to Roszdravnadzor, appointing qualified persons responsible for pharmacovigilance, and obtaining access to the Pharmacovigilance database of Roszdravnadzor’s Automated Information System. This article provides a detailed description of tools for establishing an effective pharmacovigilance system in a medical organisation, as well as the focus areas for organising pharmacovigilance in medical organisations, identified by analysing the experience of a territorial entity of the Russian Federation.CONCLUSIONS. To improve the effectiveness of pharmacovigilance in medical organisations, it is necessary to ensure the quality, integrity, and completeness of data submitted in spontaneous ADR reports. Spontaneous reporting should be supplemented with active surveillance methods, including the Global Trigger Tool. The current pharmacovigilance system in Moscow demonstrates a steady increase in reporting ADRs to Roszdravnadzor.

Exploring the complexities of disproportionality analysis in pharmacovigilance: reflections on the READUS-PV guideline and a call to action.

The use of disproportionality analysis (DA) in pharmacovigilance to detect signals of disproportionate reporting (SDRs) has gained popularity, resulting in a surge of publications based on aggregate analysis of spontaneously reported adverse events (AE). The recently published READUS-PV guideline, designed to standardize reporting practices of DA-based publications, is a commendable first step toward standardizing DA reporting; however, it will not overcome totally many of the inherent limitations of DA including their inability to eliminate unnecessary noise in order to identify true signals. The limitations arise from the data sources of AEs, the analytic approaches, and the interpretability of the results. This article discusses those limitations, highlights the challenges posed by the premature publication of safety signals derived from spontaneous reports, and evaluates the READUS-PV guideline's potential to improve interpretation of DA results. The article emphasizes that effective reporting of safety signals is only the first step; a broader, coordinated effort is necessary to establish clear scientific boundaries on what aspects of signal detection should be publicly shared to prevent unwarranted alarm and misinterpretation. It proposes the formation of a consortium, or a similar effort, led by regulators and involving academia and industry, to develop standards for the responsible validation and sharing of safety signal data.

Medication Errors Associated with the Use of Levofloxacin: An Analysis of the National Database of Spontaneous Reports

INTRODUCTION. Newly identified risks associated with the use of fluoroquinolones and the spread of antimicrobial resistance make the identification and analysis of medication errors (MEs) in prescribing fluoroquinolones especially important for providing rational antibiotic therapy. Fluoroquinolones that are most commonly used in real-world clinical settings include levofloxacin.AIM. This study aimed to examine the pattern of MEs associated with fluoroquinolones, exemplified by levofloxacin, through an analysis of spontaneous reports (SRs) submitted to the Russian pharmacovigilance database.MATERIALS AND METHODS. The authors retrospectively analysed the SRs of adverse drug reactions (ADRs) submitted to the Russian pharmacovigilance database between 1 April 2019 and 28 February 2023. According to the selected inclusion criteria, the study focused on the SRs that specified levofloxacin as a suspect medicinal product and described ADRs that took place in the Russian Federation. ME identification used summaries of product characteristics for levofloxacin approved in Russia, official clinical guidelines, and the antimicrobial stewardship guidelines Strategy for the Control of Antimicrobial Therapy (SCAT).RESULTS. The analysis included 950 SRs. MEs were identified in 307 (32.3%) of these SRs, and the total number of MEs was 332. MEs associated with the selection of the medicinal product included prescribing levofloxacin to patients without an indication for antibacterial therapy (38.9%, n=129, with 76.0% of cases being viral infections), incorrect selection of levofloxacin as a first-line antibacterial agent (18.1%, n=60), and irrational and excessive prescribing of levofloxacin in combination with other antibacterial agents (15.4%, n=51). Less frequently identified MEs were related to inappropriate dosing (13.0%, n=43), levofloxacin use in patients with contraindications (8.7%, n=29), and incorrect selection of the route of administration (3.9%, n=13) and the dosage form (2.1%, n=7).CONCLUSIONS. According to the results of this study, the practice of prescribing antibacterial agents for viral infections persists despite strong evidence of ineffectiveness in such cases. Antibacterial agents can be used effectively and safely only if prescribed for approved indications, administered at recommended doses, and delivered via specified routes of administration. The overuse of antibiotics may have negative sequelae not only for the health of an individual patient but for the health of the general population because of the increased risk of antimicrobial resistance. Therefore, there is a need to develop measures to limit the excessive use of antibiotics.

Risk of medication-induced lactic acidosis and hyperlactatemia: a pharmacovigilance study of the United States Food and Drug Administration's Adverse Event Reporting System database.

Lactic acidosis and hyperlactatemia (LAHL) are predictors of poor clinical outcomes in critically ill patients. This research aimed to specify medications reported in association with LAHL, thus providing valuable insights into medication safety. Spontaneous reports were excavated from the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database from Q1 2004 to Q2 2024. Adverse reaction signals of medication-induced lactic acidosis and hyperlactatemia (MILAHL) were detected by reporting odds ratio (ROR) and proportional reporting ratio (PRR). 1,055 medications were identified as primary suspect medications of LAHL from Q1 2004 to Q2 2024, of which 180 were considered to have risk signals by ROR and 160 by PRR. Metformin (16,439 cases), linezolid (815 cases), amlodipine (646 cases), salbutamol (531 cases), and paracetamol (417 cases) were the top 5 medications with the most cases of LAHL. Among the top 50 medications with the strongest ROR and PRR signal, 16 were systemic antivirals, and 13 were antidiabetics (9 containing metformin). 23 of the top 50 medications with the strongest ROR and PRR signal did not indicate the risk of LAHL in the Summary of Product Characteristics (SmPC). This study listed high-risk medications by ROR and PRR analysis, especially those without an LAHL warning in SmPC, to help health professionals identify MILAHL in case of elevated lactate and enhance medication safety monitoring.

Timing Matters: Exploring the Role of the Time to Onset in Recall Bias for Adverse Events Following Immunization (AEFIs) of COVID-19 Vaccines from Spontaneous Reports

Timing Matters: Exploring the Role of the Time to Onset in Recall Bias for Adverse Events Following Immunization (AEFIs) of COVID-19 Vaccines from Spontaneous Reports

Methotrexate-related drug reactions on kidneys and liver in rheumatoid arthritis: an analysis of spontaneous reports in EudraVigilance

ObjectiveMethotrexate (MTX), a standard treatment for rheumatoid arthritis (RA), is known for its potential kidney and liver toxicity. Whether concomitant use of analgesics, possibly affecting the same organs, has an impact on the occurrence or course of adverse drug reactions (ADRs) remains unclear.MethodsWe used all spontaneous reports (until 2022) of suspected ADRs associated with MTX in RA patients, from the EudraVigilance database, a spontaneous report system operated by the European Medicines Agency (EMA). We displayed case and treatment characteristics, stratified by the organ affected (kidneys, liver) and the outcome (fatal, non-fatal).ResultsWe included a total of 10,319 reports (mean age: 62.3 years, 72.6% female). 365 and 1,082 were related to ADRs involving the kidneys and liver, respectively. Patients with ADRs on the kidneys were older and comedication (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, metamizole and corticosteroids) was more common than in cases with ADRs on the liver. More patients with kidney- than liver-related ADRs had a fatal outcome (21.1% vs. 5.8%). In fatal cases with ADRs on the kidneys and with ADRs on the liver comedication was more common compared to non-fatal cases.ConclusionLiver dysfunction was reported nearly three times more often than renal impairment. However, the kidneys need to be especially watched for, since a fatal outcome was considerably more common in renal failure. More precise and standardized recommendations on renal function tests might be necessary to support physicians in the complex treatment of RA.

The safety assessment of ustekinumab on psoriasis and psoriatic arthritis: A real-world analysis based on the FDA adverse event reporting system database.

The safety assessment of ustekinumab on psoriasis and psoriatic arthritis: A real-world analysis based on the FDA adverse event reporting system database.

Rotigotine safety in real-world settings: a pharmacovigilance study using FAERS data

BackgroundThis pharmacovigilance study aims to assess adverse reactions to rotigotine based on spontaneous reports in the FDA Adverse Event Reporting System (FAERS) database, providing insights for clinical dosing.MethodsWe conducted a retrospective analysis using FAERS data from Q2 2007 to Q2 2024, employing four disproportionality analysis methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multinomial Gamma Poisson Shrinkage (MGPS). These methods were utilized to detect and evaluate adverse events (AEs) associated with rotigotine.ResultsThe dataset retrieved from the FAERS, encompassing 17,522,075 reports, a subset of 7,570 AE reports specifically implicated rotigotine. Upon analysis, 172 preferred terms (PTs) exhibited significant disproportionality and were consistently identified by the four employed algorithms. Particularly, product adhesion issue(N = 1,336, ROR 115,28 [108.94–121.98], PRR 108.46 [135850.43], EBGM 103.57 [98.79], IC (5.03) [5.03]) emerged as the predominant AE. Serious and unexpected AEs, such as drug ineffectiveness(N = 651, ROR 1.32 [ 1.22–1.43], PRR 1.31 [50.04], EBGM 1.31 [1.23], IC 0.39 [-1.27]), fall incidents(N = 361, ROR 2.93 [2.64–3.25 ], PRR 2.9 [451.76], EBGM 2.9 [2.66], IC 1.54 [-0.13]), and Parkinson’s disease(N = 345, ROR 51.57 [46.31–57.42], PRR 50.79 [16476.71], EBGM 49.7 [45.43], IC 5.64 [3.97], were also recorded.The majority of these AEs were reported within the initial 30 days of therapy (n = 298, 22.1%), whereas a significant number were noted after 360 days of treatment (n = 507, 36.2%). The median time to the onset of AEs was 213 days.ConclusionOur findings, which align with the established safety profile of rotigotine, reveal the presence of unexpected serious AEs and emphasize the importance of continued vigilance in post-marketing surveillance.

Enhancing Clarity in Dynamic Myelography Reporting: Results of a Survey of Patients and Referring Providers Evaluating a Standardized Reporting System in the Myelographic Workup of Patients with Suspected Spontaneous Intracranial Hypotension.

Dynamic myelography is a critical diagnostic tool for identifying cerebrospinal fluid (CSF) leaks, yet the current lack of standardized reporting can lead to variability in both clinical decision-making and patient understanding. To address these issues, we developed the Spontaneous Intracranial Hypotension Reporting and Data System (SIH-RADS), a standardized scoring system designed to categorize findings on dynamic myelography based on the degree of diagnostic certainty. We then administered a survey to patients and referring providers in order to evaluate the perceived value, clarity, and impact of SIH-RADS on patient and provider experiences as an adjunct to traditional reporting methods for dynamic myelography. The SIH-RADS scoring system was developed as a collaborative effort between patients and physicians, with six categories ranging from "Definite Positive with Precise Localization" (SIH-RADS 5) to "Technical Failure" (SIH-RADS 0). Surveys were distributed to three groups: (1) patients who had undergone myelography at our institution for suspected SIH, (2) anonymous patients via private spinal CSF leak groups on social media who had previously undergone myelography, and (3) referring providers who order myelograms for SIH evaluation. Survey questions assessed understanding of traditional reports, clarity of the SIH-RADS system, its impact on decision-making, and preferences for future reporting. Statistical comparisons between local and anonymous patient responses were performed using chi-square tests for categorical variables and t-tests for continuous variables. The observational study STROBE Checklist was utilized, with the proposed methodology followed. A total of 125 patients (78 local patients, 47 anonymous patients) and 13 providers participated in the survey. Among patients, 77% expressed a preference for SIH-RADS over traditional reporting methods, and 58% believed it would improve their understanding of myelography results. Among providers, 92% favored adopting SIH-RADS for future reports, with 85% rating it as very or extremely useful for guiding clinical decisions. 92% of providers reported that the standardized system would enhance communication with patients. Qualitative feedback emphasized the benefits of clearer categorization and actionable recommendations, while also highlighting opportunities to refine patient-facing language and address ambiguities in intermediate scores. A structured reporting system improves the perceived clarity, utility, and communication of dynamic myelography findings among both patients and providers. CSF = cerebrospinal fluid; SIH = spontaneous intracranial hypotension; CVF = CSF venous fistula.

Oxaliplatin-induced peripheral nerve injury in real-world clinical practice

Cancer is a public health problem and the leading cause of death for patients worldwide. In 2018, about 18 million new cases of cancer and 9.6 million deaths were registered in the world. Platinum-based drugs, as the main drugs in chemotherapy for cancer patients, are widely used in the treatment of various malignant tumors. Oxaliplatin is a third-generation cytotoxic platinum compound, widely utilized in the treatment of various oncological diseases. It is known that the main spectrum of adverse reactions (AR) of oxaliplatin includes neuro- and hematotoxicity, toxic manifestations from the gastrointestinal tract, and hypersensitivity reactions. The most significant manifestation of oxaliplatin neurotoxicity is peripheral nerve damage, the frequency of which accounts for ≥10%, according to the results of safety assessment in clinical trials [1–4] and meta-analyses [5]. There are two forms of neurotoxicity: acute and chronic. Acute neurotoxicity occurs in more than 90% of patients, may debut even during drug infusion, and usually spontaneously resolves in a short time. Chronic neurotoxicity is cumulative, and it is more often observed in patients who received oxaliplatin in a course dose of >540 mg/m2. Despite the sensory nature of neuropathy, it can lead to impairment of physical functions and significantly reduce the quality of life of patients. The safety of oxaliplatin in the Russian Federation has been assessed only in the framework of clinical trials with a small number of participants (less than 100 subjects in each) [7,8]; large-scale clinical trials have not been conducted. Spontaneous reports (SRs) of ADRs are one of the effective systems for assessing the current safety status of drugs without time and sample size restrictions. In addition, analysis of the spectrum of ADRs in SRs can allow assessing the effectiveness of routine measures to prevent the risks of pharmacotherapy, which, in relation to oxaliplatin, includes peripheral nerves injury.

Pharmacotherapy’s safety audit at the outpatient clinic level

Objective: to analyze the structure of drug prescriptions and adverse drug reactions (ADRs) in the conditions of application of the developed risk-based approach to the audit of pharmacotherapy in patients of outpatient clinics. Materials and methods: the basis for the study was an outpatient clinic in Rostov-on-Don. The sample consisted of 680 patients observed by a general practitioner. Based on the results of a retrospective analysis of spontaneous reports of ADRs registered in the Rostov region for 2019-2021, a risk-based questionnaire was developed. 50 % (n = 340) of the observed patients were surveyed and, depending on the results, pharmacotherapy was adjusted; the other half of the patients (n = 340) were not questioned and received standard pharmacotherapy. Statistical processing of the results was carried out on a PC using the LibreOffice Calc software package and IBM SPSS Statistics v. 26. Results: the overall incidence of ADR development in outpatient clinics was 7.5 % (4.5 % and 8.2 %, respectively) (p < 0.05). Patients who underwent a risk-based audit of drug prescriptions had higher rates of the psychological component of health (84.8 ± 3.2 versus 73.2 ± 2.4, respectively) (ρ = 0.386; p = 0.01), the physical component of health (78.3 ± 2.6 versus 69.4 ± 1.8, respectively) (ρ = 0.493; p = 0.01), less drug burden (3.1 ± 1.4 versus 5.3 ± 2.1, respectively) (ρ = 0.452; p = 0.01), the number of unscheduled visits to a therapist (by 24 % on average), the incidence of serious ADRs (by 18 %) (ρ = 0.949; p = 0.01), additional treatment costs (by 23 % on average) (ρ = 0.334; p = 0.01). Conclusions: the results of the study can be used for further, including pharmacoeconomic studies, to improve the safety of drug therapy, avoid the “cascade of drug prescriptions” and improve the quality of life of specialized patients in outpatient clinics.

Intravitreal vascular endothelial growth factor inhibitors and cardiovascular adverse drug reactions: Added value of the data of the French pharmacovigilance spontaneous reporting assessment.

Intravitreal vascular endothelial growth factor inhibitors and cardiovascular adverse drug reactions: Added value of the data of the French pharmacovigilance spontaneous reporting assessment.

Disproportionality Analysis and Causal Inference in Drug Safety.

Disproportionality analysis is a method of safety signal detection based on quantitative analysis of spontaneous reports of adverse events. Disproportionality findings are often presented in medical publications as real-world evidence on drug safety. In this paper, we review theoretical properties of disproportionality analysis in the framework of causal inference theory. We show that measures of disproportionality can approximate the causal rate ratio for a specific drug-event combination when the study drug and the set of comparator drugs satisfy all of the following conditions: (1) there is no uncontrolled confounding for the drug-event association of interest, (2) under-reporting for the event of interest is either absent or has the same relative magnitude for the study drug and for the comparator drugs, and (3) reporting rates for all adverse events combined are the same for the study drug and for the comparator drug set. Because these conditions are typically not even approximately satisfied in practice, the overwhelming majority of disproportionality hits represent statistical noise rather than causal associations. Researchers choosing to report disproportionality findings in publications should explicitly acknowledge all key assumptions and the exploratory nature of this data-mining technique.

Early Detection of Hearing Impairment Signals Post-mRNA COVID-19 Vaccination: A Disproportionality Analysis Study on French Pharmacovigilance Database.

Improving adverse events following immunisation (AEFI) detection is vital for vaccine safety surveillance, as an early safety signal can help minimize risks. In February 2022, the World Health Organization reported a preliminary signal on sudden sensorineural hearing loss (SSNHL) following coronavirus disease 2019 (COVID-19) vaccination, 54 million persons in France received at least one dose, covering 78.8% of the population within a year. The primary objective of this study was to identify a method of disproportionality analysis capable to detect a safety signal for hearing impairment (HI) as early as possible during the initial phases of the COVID-19 vaccination campaign. Secondly, we described all cases of SSNHL reported during vaccine booster campaigns in France. Data from January 2011 to February 2022 were extracted from the French pharmacovigilance database. Cases were all spontaneous reports ofAEFI for elasomeran and tozinameran, while non-cases wereAEFIreported for other vaccines. Disproportionality analysis for HI was performed monthly during 2021, to estimate a reporting odds ratio (ROR). Four different methods were used for ROR estimation. Furthermore, we reviewed cases of SSNHL following messenger RNA COVID-19 vaccinations reported during booster campaigns, from 2 February 2022 to 1 March 2023, based on a comprehensive medical evaluation. Using a standard methodology, we identified a signal on 31 July 2021 (ROR 1.50, 95% confidence interval [CI] [1.06-2.18]). Multivariate analysis adjusted for sex, age, ototoxic drugs and excluding reference reports of common AEFI for vaccines allowed us to detect the HI signal as early as 31 March 2021 (ROR 2.67, 95% CI [1.36-5.57]). The SSNHL reporting rate was estimated to be 0.83/1,000,000 doses for tozinameran and 4.3/1,000,000 for elasomeran during the booster campaigns. Using a well-structured disproportionality analysis could have enhanced early detection of safety signals and contribute to risk minimizing measures. According to descriptive data, HI following mRNA COVID-19 vaccines remains rare.

Lung toxicity related to trimethoprim/sulfamethoxazole: pharmacovigilance data review.

Well-established side effects of trimethoprim/sulfamethoxazole include cutaneous and liver toxicity, hypersensitivity syndrome and blood dyscrasias. Trimethoprim/sulfamethoxazole has also been associated with severe lung toxicity (LT) but reports are scarce. We investigated pharmacovigilance data and reviewed spontaneous reports of trimethoprim/sulfamethoxazole-related LT recorded in the French national pharmacovigilance database (FPVD) and the WHO global database of adverse events (VigiBase®) up to 31 December 2023. We performed disproportionality analysis to detect a possible pharmacovigilance signal. A total of 755 patients with trimethoprim/sulfamethoxazole-related LT were reported in VigiBase®, 17 of which were from the FPVD. In VigiBase®, interstitial lung disease was the most frequent LT pattern (30.5%). A fatal outcome was reported in 197 patients (26.1%). Significant reporting ORs were observed for the following trimethoprim/sulfamethoxazole-related LT patterns: interstitial lung disease 1.5 (95% CI: 1.3-1.7); acute respiratory distress syndrome 2.9 (95% CI: 2.5-3.5); eosinophilic pneumonia 4.1 (95% CI: 3.2-5.2); diffuse alveolar damage 3.7 (95% CI: 2.6-5.3); organizing pneumonia 2.1 (95% CI: 1.4-3.1); pulmonary toxicity 1.9 (95% CI: 1.3-2.9); acute lung injury 7.5 (95% CI: 4.9-11.6) and hypersensitivity pneumonitis 2.7 (95% CI: 1.7-4.2). We highlight statistically significant disproportionality for several trimethoprim/sulfamethoxazole-related LT patterns, which constitutes a pharmacovigilance signal. Trimethoprim/sulfamethoxazole-related LT is rare, but may be critical and even life-threatening. Physicians should be aware of potential trimethoprim/sulfamethoxazole-related LT and should inform their patients, since early intervention could prevent severe outcome.

Аnalysis of cases of adverse reactions during the use of antiretroviral therapy in pregnant women

Antiretroviral therapy is a treatment that involves the regular use of a combination of antiviral drugs. During pregnancy, women with human immunodeficiency virus (HIV) do not stop antiretroviral treatment, as this is necessary to reduce the risk of HIV transmission from the mother to the fetus. However, the body of a pregnant woman can affect the way the antiretroviral medications work, called their pharmacokinetics and pharmacodynamics. This can increase the risk of adverse drug reactions (ADR) from the medications.The aim of the study was investigated of the frequency of ADR of antiretroviral therapies based on analysis of spontaneous reports of ADR among pregnant women who were registered in the ARCADe regional database (Adverse Reactions in Crimea, Autonomous Database). Materials and methods. The study included 64 spontaneous ADR reports registered in the electronic database of spontaneous ARCADE messages in the Republic of Crimea between January 1, 2012 and December 31, 2021. These reports were collected from pregnant women who were taking ARP.Results and discussion. The most common types of ADR have been reported when using combined antiretroviral medications and nucleoside reverse transcriptase inhibitor drugs. The combination of lamivudine and zidovudine drugs was the most frequent cause of adverse effects among pregnant women on antiretroviral therapy. Hematopoietic disorders and dyspepsia were the most prevalent clinical manifestations of the ADR. Almost 85% of identified ADR required medication adjustment, although only 5% were classified as severe manifestations of the events.Conclusion. Long-term antiretroviral drug use requires regular monitoring of ADR, particularly during pregnancy, to provide timely care and maintain high levels of patient adherence to an effective antiretroviral treatment regimen. Despite the high incidence of anemia, skin, and dyspeptic problems, the proportion of serious ADR was found to be relatively low, which justifies the use of antiretroviral therapy during pregnancy. This justifies the continued use of antiretroviral therapy during pregnancy, as it has undeniable benefits in preventing transmission of HIV from mother to child, suppressing viral replication, and reducing mortality in infants.

The Assessment of the Safety Profile of Selective Serotonin Reuptake Inhibitors Versus Other Antidepressants: Drug-Drug Interaction Insights from EudraVigilance.

Depression persists as one of the illnesses described relentlessly through the centuries because it affects a large group of people. Background/Objectives: The treatment of depression consists of various therapeutic agents, among which selective serotonin reuptake inhibitors (SSRIs) are elective. As polypharmacy tends to become the norm in modern days, the study of the real-life occurrence of drug-drug interactions is imperative. The aim of this study was the evaluation of drug-drug interactions (DDIs) between antidepressant medicines, namely SSRIs (each representative) versus eleven representatives from other antidepressant classes. Methods: Based on the spontaneous safety reports (ICSRs) uploaded to EudraVigilance until the end of July 2024, the descriptive and the disproportionality analyses were performed, and results were interpreted in the context of pharmacologic variability. Results: SSRIs were the focus of 137,369 ICSRs while for the other antidepressants, namely amitriptyline, clomipramine, duloxetine, venlafaxine, mirtazapine, bupropion, trazodone, tianeptine, agomelatine, brexpiprazole, and esketamine, a total of 155,458 reports were registered. The most notable differences appeared in psychiatric adverse drug reactions. Except fluvoxamine (n = 463), the remaining SSRIs had a higher number of DDIs reported (n = 1049 for escitalopram and n = 1549 for sertraline) compared to other antidepressants. However, similar numbers of DDIs were reported for duloxetine (n = 1252) and venlafaxine (n = 1513). Sertraline unspecified DDIs were reported with a higher probability compared to all other drugs (e.g., esketamine ROR: 9.37, 95% CI: 5.17-16.96, tianeptine ROR: 4.08, 95% CI: 2.49-6.69, etc.). Conclusions: SSRIs, although known to influence various cytochrome P450 isoenzymes, have not shown higher inhibitory interactions compared to any of the drugs selected as reference. Sertraline appears in more reports concerning DDIs than the other antidepressants. Still, further real world studies related to the DDIs of SSRIs are needed to complete the relevant knowledge level.