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European Heart Journal. Cardiovascular... Jun 2024To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical...
AIMS
To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice.
METHODS
Cohort study using data from nationwide registers in Sweden, Denmark and Norway, from June 2014 to June 2021 including 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death and diabetic ketoacidosis.
RESULTS
Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events (adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, [95% CI 0.97-1.08]), heart failure (6.5 vs. 6.3 events per 1000 person-years; HR 1.05 [0.97-1.14]) and serious renal events (3.7 vs. 4.1 events per 1000 person-years; HR 0.97 [0.87-1.07]). In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis.
CONCLUSIONS
Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality and diabetic ketoacidosis.
PubMed: 38918063
DOI: 10.1093/ehjcvp/pvae045 -
Cureus May 2024While drugs are intended to benefit patients, adverse drug reactions (ADRs) represent a significant negative outcome of drug consumption. They rank as the sixth...
INTRODUCTION
While drugs are intended to benefit patients, adverse drug reactions (ADRs) represent a significant negative outcome of drug consumption. They rank as the sixth leading cause of death among hospitalized patients. Many harmful effects are preventable and can reduce morbidity, mortality, and hospitalization duration. This study is a valuable resource for physicians, aiding in the safe and optimal use of medications.
METHODOLOGY
This retrospective observational study, conducted at the Pharmacovigilance Center of Saveetha Medical College and Hospital, Chennai, India, received approval from the Institutional Ethics Committee. All adverse drug interactions reported in our hospital from January 2019 to February 2024 were included after screening for inclusion and exclusion criteria. The collected reactions were analyzed, assessed, and evaluated between February 2024 and April 2024. Data on the drugs causing adverse reactions, the types of reactions, and the treatments administered were collected and documented. The reactions were categorized using the Rawlins and Thompson classification, while causality and severity were assessed using the standard Naranjo causality and modified Hartwig and Siegel severity assessment scales.
RESULTS
During the study, 252 ADRs were documented by the Central Drugs Standard Control Organization. The gender distribution showed 123 cases (48.8%) in males and 129 cases (51.2%) in females, with a higher prevalence in the 20-40 age group. The departmentwise distribution revealed the highest number of ADRs in Obstetrics and Gynecology (60 cases, 24%), followed by General Surgery (52 cases, 21%), General Medicine (44 cases, 17%), Pediatrics (22 cases, 9%), and Emergency Medicine (20 cases, 8%). Antimicrobial drugs constituted the majority of ADRs (149 cases, 59.1%), followed by vitamins and mineral supplements (21 cases, 13.8%), contrast dye (15 cases, 6%), antituberculosis drugs (15 cases, 6%), analgesics (13 cases, 5.2%), and gastrointestinal (GIT) drugs (8 cases, 3.2%). Cefotaxime was the most commonly reported antibiotic (42 cases, 28.2%), followed by Ciprofloxacin (41 cases, 27.5%). Among vitamins and mineral supplements, iron sucrose was implicated in the highest number of ADRs (15 cases, 71.4%). The parenteral route of drug administration showed the highest incidence of ADRs (229 cases, 91%), followed by oral (20 cases, 8%) and topical routes (3 cases, 1%). Dermatological manifestations were most frequently reported (196 cases, 77.8%), followed by GIT symptoms (27 cases, 10.7%), and other manifestations such as shivering, fever, seizures, and dyspnea (29 cases, 11.5%). Based on the Naranjo causality assessment scale, 179 ADRs (71%) were categorized as probable, 55 (22%) as possible, 10 (4%) as certain, and 8 (3%) as doubtful. Approximately 47.2% of ADRs were self-limiting, while 44.1% required symptomatic treatment and 8.7% necessitated aggressive treatment, leading to a prolonged hospital stay or admission to the intensive care unit.
CONCLUSION
The pattern of ADRs in our hospital aligns with findings from other studies. While many of these reactions are unpredictable and mild, they underscore the importance of raising awareness among clinicians and regulatory authorities to promote safe medication use and prevent potentially serious outcomes.
PubMed: 38915954
DOI: 10.7759/cureus.60977 -
Frontiers in Pharmacology 2024To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better...
OBJECTIVE
To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
METHODS
Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
RESULTS
Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the "primary suspected (PS)" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
CONCLUSION
Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).
PubMed: 38915470
DOI: 10.3389/fphar.2024.1358592 -
Expert Opinion on Drug Safety Jun 2024From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading... (Review)
Review
INTRODUCTION
From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading to the development of Good Signal Detection Practices. The ensuing period witnessed the independent exploration of research paths proposed by IMI PROTECT, accumulating valuable experience and insights that have yet to be seamlessly integrated.
AREAS COVERED
This state-of-the-art review integrates IMI PROTECT recommendations with recent acquisitions and evolving challenges. It deals with defining the object of study, disproportionality methods, subgrouping, masking, drug-drug interaction, duplication, expectedness, the debated use of disproportionality results as risk measures, integration with other types of data.
EXPERT OPINION
Despite the ongoing skepticism regarding the usefulness of disproportionality analyses and individual case safety reports, their ability to timely detect safety signals regarding rare and unpredictable adverse reactions remains unparalleled. Moreover, recent exploration into their potential for characterizing safety signals revealed valuable insights concerning potential risk factors and the patient's perspective. To fully realize their potential beyond hypothesis generation and achieve a comprehensive evidence synthesis with other kinds of data and studies, each with their unique limitations and contributions, we need to investigate methods for more transparently communicating disproportionality results and mapping and addressing pharmacovigilance biases.
PubMed: 38913869
DOI: 10.1080/14740338.2024.2368817 -
JAMA Internal Medicine Jun 2024
PubMed: 38913358
DOI: 10.1001/jamainternmed.2024.1833 -
Drug, Healthcare and Patient Safety 2024The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel...
BACKGROUND
The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel oral polio vaccine type 2 (nOPV2), raised concerns about adverse events following immunization (AEFI) surveillance. We assessed the attributes of AEFI with nOPV2 and examined stakeholder experiences and challenges in AEFI surveillance in Sierra Leone.
METHODS
Using a mixed method approach, we retrospectively reviewed passive data collected during a 2021 immunization campaign, and conducted semi-structured, interviews with vaccinators, district AEFI focal persons, and key stakeholders at the national Expanded Program on Immunization and the National Medicines Regulatory Authority. AEFI were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) and System Organ Class (SOC). Outcomes were stratified as recovered or not, with preventability and causality assessed using the Schumock and Thornton and World Health Organization (WHO) algorithms, respectively.
RESULTS
A total of 528 suspected AEFI were documented, predominantly affecting children aged 28 days to 23 months (63.3%). Most reported AEFI were administration site conditions and general disorders, with pyrexia being the predominant PT. Of 80 serious cases, 78 recovered, with 74 having an inconsistent causal relationship with the vaccine. Most serious cases (78) were deemed non-preventable, with only two being probably preventable. AEFI reporting was not routinely carried out across the group of people interviewed. AEFI reporting was not consistently performed, with discrepancies in defining reportable events and confusion over responsibility. Challenges with the open data kit (ODK) platform were noted, along with perceived inadequacies in training.
CONCLUSION
While the nOPV2 is relatively new, the majority of AEFI were not serious, and most serious cases were not causally linked to the vaccine. Participants exhibited variations in experience and awareness of AEFI reporting.
PubMed: 38911456
DOI: 10.2147/DHPS.S466039 -
Severe Hypertriglyceridemia in a Patient With Metabolic Syndrome and Psoriasis on Risankizumab-Rzaa.JCEM Case Reports Jun 2024We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male...
We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male with a history of longstanding uncontrolled type 2 diabetes, obesity, and coronary artery disease with prior ST-elevation myocardial infarction. On admission, the patient presented with xanthomatous plaques, chest and epigastric discomfort, and headache. Subsequent blood testing revealed severely elevated triglyceride (TG) levels at 7670 mg/dL (86.59 mmol/L) [reference range: <150 mg/dL; 1.69 mmol/L] and total cholesterol at 934 mg/dL (24.14 mmol/L) [reference range: <200 mg/dL; 5.17 mmol/L]. Triglyceride levels decreased and symptoms resolved with dietary restrictions and plasmapheresis. At follow-up, his TG remained elevated but improved, and he was advised to continue lipid-lowering medications as well as cessation of risankizumab. While the patient presented with high risk factors, we posit that the subacute presentation of severe HTG is a possible result of his recent course of risankizumab-rzaa therapy for management of psoriasis. This is noteworthy as pharmaceutical surveys and clinical trials do not list severe HTG as an adverse effect. Postmarketing surveillance studies are essential to confirm this potential association and monitor drug safety. In summary, this case highlights a possible link between risankizumab and severe HTG, emphasizing the importance of ongoing pharmacovigilance to identify and manage unexpected adverse effects associated with new medications.
PubMed: 38911361
DOI: 10.1210/jcemcr/luae087 -
Frontiers in Pharmacology 2024Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight...
BACKGROUND
Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight management in adults with obesity or overweight as an adjunct to a reduced-calorie diet and increased physical activity. However, the safety profile of Tirzepatide-associated adverse events requires comprehensive evaluation.
METHODS
The AE reports from the first quarter of 2022 to the third quarter of 2023 were selected by exploring the FDA Adverse Event Reporting System (FAERS) database. The new and unexpected potenial AE signals were detected using the disproportionality analysis, including reporting odds ratio(ROR), the proportional reporting ratio (PRR) the Bayesian confidence propagation neural network (BCPNN) and the empirical Bayes geometric mean(EBGM). Then the MedDRA was used to systematically classify the results.
RESULTS
A total of 1,904,481 case reports were obtained from 2022Q2 to 2023Q3. Forty-sixth tirzepatide-induced ADRs at the preferred terms (PTs) level are associated with 8 system organ class In addition, this study uncovered multiple anticipated ADRs, such as gastrooesophageal reflux disease, dyspepsia, and vomiting, in line with the drug labels. Moreover, unexpected and significant ADRs at PTs level, such as incorrect dose administered, injection site haemorrhage, and increased appetite, were discovered and linked to Injury, poisoning, and procedural complications, General disorders and administration site conditions, and Metabolism and nutrition disorders at the System Organ Class level.
CONCLUSION
This study offered new perspectives on the monitoring, surveillance, and management of adverse drug reactions related to tirzepatide. The outcomes of severe adverse events and their respective detection signals, along with unexpected significant adverse event signals, are important to consider in efforts to enhance clinical medication safety when using tirzepatide.
PubMed: 38910884
DOI: 10.3389/fphar.2024.1397029 -
Drug Safety Jun 2024The safety profile of COVID-19 vaccines in immunocompromised patients has not been comprehensively evaluated.
BACKGROUND
The safety profile of COVID-19 vaccines in immunocompromised patients has not been comprehensively evaluated.
AIM
To measure the frequency of patient-reported adverse drug reactions (ADRs) related to the first/second/booster dose of COVID-19 vaccine in immunocompromised subject versus matched cohort. As a secondary objective, the time course, evaluated as time to onset (TTO) and time to recovery (TTR), of COVID-19 vaccine-related ADRs was explored.
METHODS
A prospective cohort study, based on electronic questionnaires filled by vaccinees from 11 European countries in the period February 2021 to February 2023 was conducted. All immunocompromised vaccinees who provided informed consent and registered to the project's web-app within 48 h after first/booster vaccine dose administration of any EMA-authorised COVID-19 vaccine were recruited. Participants filled baseline and up to six follow-up questionnaires (FU-Qs) over 6 months from vaccination, collecting information on suspected COVID-19 vaccine-related ADRs. As a control group, non-immunocompromised vaccinees from the same source population were 1:4 matched by sex, age, vaccine dose, and brand. A descriptive analysis of demographic/clinical characteristics of vaccinees was conducted. Heatmaps of the frequency of solicited ADRs, stratified by gender and vaccine brand, were generated. Median TTO/TTR of reported ADRs were visualised using violin/box-plots.
RESULTS
A total of 773 immunocompromised vaccines were included in the analyses. Most participants were females (F/M ratio: 2.1 and 1.6) with a median age of 56 (43-74) and 51 (41-60) years, at the first vaccination cycle and booster dose, respectively. Injection-site pain and fatigue were the most frequently reported ADRs in immunocompromised vaccinees with higher frequency than matched control, especially after the first dose (41.2% vs 37.8% and 38.2% vs 32.9%, respectively). For both cohorts, all solicited ADRs were more frequently reported in females than males, and in those who had received a first dose of the Vaxzevria vaccine. Dizziness was the most frequently reported unsolicited ADR after the first dose in both groups (immunocompromised subjects: 2.5% and matched controls: 2.1%). At the booster dose, lymphadenopathy (3.9%) and lymphadenitis (1.8%) were the most reported unsolicited ADRs for immunocompromised subjects and matched controls, respectively. A very low number of subjects reported adverse event of special interest (AESI) (2 immunocompromised, 3 matched controls) and serious ADRs (5 immunocompromised, 5 matched controls). A statistically significant difference among study cohorts was observed for median TTO after the booster dose, and for median TTR after the first vaccination cycle and booster dose (p < 0.001).
CONCLUSION
The overall safety profile of COVID-19 vaccines in immunocompromised people was favourable, with minor differences as compared to non-immunocompromised vaccinees. Participants mostly experienced mild ADRs, mainly reported after the first dose of Vaxzevria and Jcovden vaccines. Serious ADRs and AESI were rare.
PubMed: 38907947
DOI: 10.1007/s40264-024-01449-x -
Drug Safety Jun 2024Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude... (Review)
Review
INTRODUCTION
Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs.
METHODS
We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources.
RESULTS
We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries.
CONCLUSION
The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.
PubMed: 38907172
DOI: 10.1007/s40264-024-01445-1