-
Frontiers in Pharmacology 2023The risk of falls and bone fractures with sodium-glucose co-transporter-2 (SGLT2) inhibitors has been characterized by conflicting evidence. Therefore, we decided to...
The risk of falls and bone fractures with sodium-glucose co-transporter-2 (SGLT2) inhibitors has been characterized by conflicting evidence. Therefore, we decided to investigate the reporting probability of falls and fractures by comparing SGLT2 inhibitors with DPP4 inhibitors. A retrospective, pharmacovigilance study of the European database of Individual Case Safety Reports (ICSRs) was conducted. Disproportionality analyses (Reporting Odds Ratio, ROR) were conducted to compare the reporting probability of falls or fracture between treatments. A total of 507 ICSRs reporting at least one fall or fracture with SGLT2 inhibitors were identified. The most reported SGLT2 inhibitor was canagliflozin ( = 188; 36.9%), followed by empagliflozin ( = 176; 34.5%), and dapagliflozin ( = 143; 28.0%). A total of 653 events related to fall or bone fracture were reported. Fall was the most reported event ( = 333; 51.0%). Among fractures ( = 320; 49.0%), the most reported were foot fractures ( = 40; 6.1%) and hip fractures ( = 32; 4.9%). SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors (ROR, 0.66; 95%CI, 0.57-0.78). The lower reporting probability of fall was also observed when the single SGLT2 inhibitor was compared to DPP4 inhibitors: dapagliflozin (ROR, 0.67; 95%CI, 0.53-0.83), canagliflozin (ROR, 0.56; 95%CI, 0.45-0.70), and empagliflozin (ROR, 0.77; 95%CI, 0.63-0.94). For fractures, canagliflozin showed a slightly significant increased reporting when compared with DPP4 inhibitors (not confirmed in the sensitivity analysis), whereas all other comparison showed no statistically significant difference. SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors, in accordance with the reassuring evidence about the safety profile of these drugs. Future researches will help to confirm their long-term safety profile.
PubMed: 38027019
DOI: 10.3389/fphar.2023.1245642 -
Frontiers in Pharmacology 2023Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is authorized for the treatment of chronic lymphocytic leukemia (CLL). This study aims to explore the cardiac...
Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is authorized for the treatment of chronic lymphocytic leukemia (CLL). This study aims to explore the cardiac safety profile of ibrutinib in comparison with obinutuzumab. A retrospective pharmacovigilance study was conducted on data retrieved from the European pharmacovigilance database (Eudravigilance) from 1 January 2014 to 30 September 2022. To compare the reporting frequency of cardiovascular events among ibrutinib, obinutuzumab, and the combination of both. A total of 2 291 CV cases were retrieved, of which 1965 were related to ibrutinib, 312 to obinutuzumab, and 14 to the combination. Most cases referred to patients aged ≥65 years ( = 1,454; 63.47%) and male ( = 1,497; 65.34%). Most cases were serious ( = 2,131; 93.02%). The most reported events were: atrial fibrillation ( = 913; 31.31%) and haemorrhage ( = 201; 6.89%). A higher reporting frequency of CV events was found when ibrutinib was compared to obinutuzumab (ROR, 3.22; 95% CI, 2.89-3.60) or combination (ROR, 1.77; 95% CI, 1.11-2.83). A lower reporting was observed when obinutuzumab was compared to combination (ROR, 0.55; 95% CI, 0.34-0.88). A higher reporting frequency of CV events in patients exposed to ibrutinib in comparison with obinutuzumab was found. Further studies are needed to better explore the safety of ibrutinib.
PubMed: 37654615
DOI: 10.3389/fphar.2023.1229304 -
Therapeutic Innovation & Regulatory... Mar 2024Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare... (Review)
Review
Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare professionals. Understanding the current regulatory landscape in the clinical trial and postmarketing settings is critical to facilitate the development of applicable processes and tools for studying medicine use during pregnancy and breastfeeding and comply with health authority expectations. This review summarizes key findings from a landscape assessment of regulations, guidelines, and guidance on the use of medicines in pregnancy and breastfeeding issued by health authorities in various territories (including the Americas, Europe, Africa, and Asia Pacific) and outlines relevant initiatives undertaken by health authorities, academic institutions, industry consortia, and public-private organizations. While global pharmacovigilance legislation regarding medication use during pregnancy and breastfeeding exists and continues to evolve, the landscape assessment revealed that there is a lack of global legislative harmonization in both the clinical trial and postmarketing surveillance settings and regulatory gaps still exist in many countries/regions. Despite ongoing efforts from health authorities and public and private organizations, intensive efforts for legislation harmonization and stakeholder collaboration are required to improve the current environment of medication safety in pregnancy and breastfeeding.
Topics: Humans; Female; Pregnancy; Infant, Newborn; Infant Health; Pharmacovigilance; Asia; Europe
PubMed: 38105314
DOI: 10.1007/s43441-023-00593-3 -
Advances in Pharmacological and... 2023This exploratory qualitative study aimed to analyze the experiences of healthcare providers (HCPs) in pharmacovigilance (PV) and ADR reporting in the southern highland...
PURPOSE
This exploratory qualitative study aimed to analyze the experiences of healthcare providers (HCPs) in pharmacovigilance (PV) and ADR reporting in the southern highland zone of Tanzania.
METHODS
In 2022, an exploratory qualitative case study using in-depth interviews (IDIs) was conducted to explore the experiences of PV and ADR reporting among HCPs (doctors, nurses, and pharmacists). The study was carried out in a zonal referral hospital and a regional referral hospital of the Tanzanian southern highlands zone. Inductive-deductive thematic analysis was adopted for data analysis.
RESULTS
Participants demonstrated adequate knowledge of PV and its related activities including ADR reporting. Knowing the interactions and wrong medication dosage as sources of ADR, signs, and symptoms, stopping the drug, and treating the symptoms following ADR emerged as subthemes linked with adequate knowledge in identifying and managing ADR. Participants perceived reporting ADR as laborious, posing a subjective burden and that not all ADRs needed to be reported. The latter contributed to limited participation in ADR reporting despite that participants were conversant with both physical and online ADR reporting platforms.
CONCLUSION
Although HCPs are well informed about PV and ADR reporting including the benefits to public health, their involvement in ADR reporting is low. In addition to the ongoing on-the-job training and regular supportive supervision for HCPs to improve the ADR practice, there is still a need to explore other strategies to be used as motives for HCPs to report ADR regularly.
PubMed: 37876921
DOI: 10.1155/2023/5537592 -
ERJ Open Research May 2024Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying...
BACKGROUND
Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. The objective of the present study was to assess the association between gemcitabine and PH.
METHODS
We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 and December 2022. The aetiology, clinical, functional, radiological and haemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the World Health Organization (WHO) pharmacovigilance database.
RESULTS
We identified nine cases of pulmonary arterial hypertension, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (range 26-47) mmHg, a cardiac index of 2.4 (1.6-3.9) L·min·m and a pulmonary vascular resistance of 6.3 (3.1-12.6) Wood units. The median time from the initiation of gemcitabine to the onset of PH was 7 (4-50) months, with patients receiving a median of 16 (6-24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.
CONCLUSION
Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnoea.
PubMed: 38770007
DOI: 10.1183/23120541.00654-2023 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice.
METHODS
Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality.
RESULTS
The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs.
CONCLUSION
These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Pharmacovigilance; United States; United States Food and Drug Administration; Randomized Controlled Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Adverse Drug Reaction Reporting Systems; Bayes Theorem; Retrospective Studies
PubMed: 38745663
DOI: 10.3389/fimmu.2024.1396752 -
JCO Clinical Cancer Informatics May 2024This new editorial discusses the promise and challenges of successful integration of natural language processing methods into electronic health records for timely,...
This new editorial discusses the promise and challenges of successful integration of natural language processing methods into electronic health records for timely, robust, and fair oncology pharmacovigilance.
Topics: Pharmacovigilance; Humans; Artificial Intelligence; Electronic Health Records; Medical Oncology; Natural Language Processing; Data Collection; Neoplasms; Adverse Drug Reaction Reporting Systems
PubMed: 38713889
DOI: 10.1200/CCI.24.00051 -
Unveiling drug induced nephrotoxicity using novel biomarkers and cutting-edge preventive strategies.Chemico-biological Interactions Jan 2024Drug-induced nephrotoxicity is still a significant obstacle in pharmacotherapy of various diseases and it accounts for around 25 % of serious side-effects reported... (Review)
Review
Drug-induced nephrotoxicity is still a significant obstacle in pharmacotherapy of various diseases and it accounts for around 25 % of serious side-effects reported after drug administration. Furthermore, some groups of drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, antiviral drugs, antifungal drugs, immunosuppressants, and chemotherapeutic drugs have the "preference" for damaging the kidney and are often referred to as the kidney's "silent killer". Clinically, the onset of acute kidney injury associated with drug administration is registered in approximately 20 % of patients and many of them develop chronic kidney disease vulnerability. However, current knowledge about the mechanisms underlying this dangerous phenomenon is still insufficient with many unknowns. Hence, the valuable use of these drugs in clinical practice is significantly limited. The main aim of this study is to draw attention to commonly prescribed nephrotoxic drugs by clinicians or drugs bought over the counter. In addition, the complex relationship between immunological, vascular and inflammatory events that promote kidney damage is discussed. The practical use of this knowledge could be implemented in the engineering of novel biomarkers for early detection of drug-associated kidney damage such as Kidney Injury Molecule (KIM-1), lipocalin associated with neutrophil gelatinase (NGAL) and various microRNAs. In addition, the utilization of artificial intelligence (AI) for the development of computer algorithms that could detect kidney damage at an early stage should be further explored. Therefore, this comprehensive review provides a new outlook on drug nephrotoxicity that opens the door for further clinical research of novel potential drugs or natural products for the prevention of drug-induced nephrotoxicity and accessible education.
Topics: Humans; Lipocalin-2; Artificial Intelligence; Kidney; Acute Kidney Injury; Drug-Related Side Effects and Adverse Reactions; Biomarkers
PubMed: 38104745
DOI: 10.1016/j.cbi.2023.110838 -
Frontiers in Pharmacology 2023This study aimed to develop active surveillance programs (ASPs) for anaphylaxis using the China Hospital Pharmacovigilance System (CHPS) and analyze the...
This study aimed to develop active surveillance programs (ASPs) for anaphylaxis using the China Hospital Pharmacovigilance System (CHPS) and analyze the characteristics, allergens, and management strategies for anaphylaxis within a tertiary hospital setting in China. We retrospectively analyzed the anaphylaxis cases reported to the National Adverse Drug Reaction Monitoring System in our hospital from 2014 to 2021. Characteristic medical orders, progress notes, and diagnoses in these cases were recorded to identify initial anaphylaxis trigger entries. Based on these initial entries, the questionnaire was developed, and the Delphi method was used to establish consensus entries for anaphylaxis triggers. The CHPS was used to program these trigger entries and construct ASPs, which were then tested on the 238,194 discharged patients to evaluate their performance and analyze the related clinical data. Ten anaphylaxis triggers and three ASPs were ultimately identified. The ASPs captured 309 cases, out of which 94 cases were confirmed as anaphylaxis following manual screening. After removing duplicates, we noted 76 patients who experienced anaphylaxis 79 times. The positive rate of triggers and the positive predictive value of the programs were 0.13% and 30.42%, respectively. The incidence of anaphylaxis in our study was 0.03%, and the number of anaphylaxis cases detected by the ASPs was 5.64 times higher than those detected by the spontaneous reporting system. Anaphylaxis was more common among female patients. Antibacterial drugs, antineoplastic drugs, and contrast media were the most prevalent allergens in clinical practice. Anaphylaxis to antineoplastic drugs had the highest incidence (0.6%) when compared with patients admitted during the same period. Our study revealed a significant underuse of epinephrine and overuse of second-line therapy (glucocorticoids and antihistamines) in the management of anaphylaxis. Furthermore, we found the use and dosage of epinephrine to be inappropriate. The CHPS can effectively utilize both structured and unstructured data to construct anaphylaxis ASPs, and this could counteract the under-reporting by the spontaneous reporting system, the primary adverse reaction monitoring method in China. The treatment and management of anaphylaxis are currently inadequate and require improvement to reduce mortality risk.
PubMed: 37497105
DOI: 10.3389/fphar.2023.1180685 -
International Journal of Clinical... Dec 2023Spontaneous reporting is the most used method to monitor post-marketing safety information. Although patient involvement in spontaneous reporting has increased overtime,... (Review)
Review
BACKGROUND
Spontaneous reporting is the most used method to monitor post-marketing safety information. Although patient involvement in spontaneous reporting has increased overtime, little is known about factors associated with patients' adverse drug reaction (ADR) reporting.
AIM
To identify and assess the sociodemographic characteristics, attitudes and knowledge that influence spontaneous reporting and the reasons associated with ADR underreporting by patients.
METHOD
A systematic review was conducted according to PRISMA guidelines. A search on the MEDLINE and EMBASE scientific databases was performed to retrieve studies published between 1 January 2006 and 1 November 2022. Studies were included if they addressed knowledge and attitudes associated with ADR underreporting.
RESULTS
A total of 2512 citations were identified, of which 13 studies were included. Sociodemographic characteristics were frequently identified with ADR reporting in 6 studies, being age (3/13) and level of education (3/13) the most often reported. Older age groups (2/13) and individuals with higher level of education (3/13) were more likely to report ADRs. Underreporting was shown to be motivated by reasons related to knowledge, attitudes, and excuses. Ignorance (10/13), complacency (6/13), and lethargy (6/13) were the most frequent reasons for not reporting.
CONCLUSION
This study highlighted the scarcity of research conducted with the aim of assessing ADR underreporting by patients. Knowledge, attitudes, and excuses were commonly observed in the decision to report ADRs. These motives are characteristics that can be changed; hence strategies must be designed to raise awareness, continually educate, and empower this population to change the paradigm of underreporting.
Topics: Humans; Aged; Surveys and Questionnaires; Adverse Drug Reaction Reporting Systems; Health Knowledge, Attitudes, Practice; Pharmacovigilance; Drug-Related Side Effects and Adverse Reactions
PubMed: 37247159
DOI: 10.1007/s11096-023-01592-y