BACKGROUND: Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population.
METHODS: We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis.
RESULTS: We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults.
CONCLUSIONS: The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms.

To specify psychoactive substances and related complications observed in spontaneous reports (SRs) in women versus men, we assessed SRs on substance-linked acute toxicity sent to a French Addictovigilance centre. Over the period 2021-2022, 880 SRs were analysed (33.4% concerned women). Severe complications concerned more men than women (70.3% versus 59.5%; p = 0.0014). In women, the main implicated substances were psychoactive medications (opioids, benzodiazepines). The most frequently reported complication was suicidal behaviour (14.6% versus 7.8%, p = 0.002). In men, SRs concerned mainly illicit substances (cocaine, amphetamines) or misuse of opioid maintenance therapy or nitrous oxide. The main complications in men were infections (12.97% versus 5.4%, p = 0.0006) and neurological troubles (37.6% versus 23.5%, p < 0.0001).Our data highlight sex/gender disparities in substance use and complications, in agreement with recent literature and French national Addictovigilance data.

In recent years, complications of drug therapy are an important medical problem. Data on adverse drug reactions (ADR) in patients of older age groups were analyzed. The object of the study was notification cards for unwanted reactions received from medical organizations of the Irkutsk region for period 2009-2020 years. The Narangio scale was used to assess the causality between ADR and medicines. Of the 1021 ADR notifications in patients over 65 years of age, 2/3 (668) are presented with ADR notifications in women, 353 (34,6%) in men. The presence of background diseases was registered in 915 notifications (89,6%). There were no gender differences except for a higher incidence of chronic obstructive pulmonary disease in men (7,2 and 3,5% respectively, p<0,05) and diabetes mellitus in women (14 and 3,5% respectively, p<0,05). ADRs for antibacterial agents amounted to 31,8%, drugs for the treatment of cardiovascular diseases - 10,5%, cases of therapeutic inefficiency - 5,1%. The ADR data statement was in line with the recommended form of 76%. The most common filling defect was incomplete patient information. The validity of the Narango causation was high. The deadlines for reporting data were observed in 89,1%. For effective interaction in the pharmacovigilance system, it is necessary in each medical organization to constantly inform about the procedure for pharmacovigilance, types of ADRs, the rules for their detection and the timing of data reporting. The work should be supervised by a trained specialist.
В последние годы осложнения лекарственной терапии являются важной медицинской проблемой. Проведен анализ данных о нежелательных реакциях лекарственных средств у пациентов старших возрастных групп. Объектом исследования были карты-извещения о нежелательных реакциях, поступившие из медицинских организаций Иркутской обл. за период 2009–2020 гг. Для оценки причинно-следственной связи между нежелательными реакциями и лекарственными средствами использовали шкалу Наранжо. Из 1 021 извещения о нежелательных реакциях у пациентов старше 65 лет было 668 (65,4%) — от женщин, 353 (34,6%) — от мужчин. Наличие фоновых заболеваний зарегистрировано в 915 (89,6%) извещениях. Не было гендерных различий, за исключением более высокой частоты ХОБЛ у мужчин — 7,2 и 3,5% у женщин соответственно (р<0,05), и сахарного диабета у женщин — 14 и 3,5% у мужчин соответственно (р<0,05). Нежелательные реакции на антибактериальные средства составили 31,8%, на препараты для лечения сердечно-сосудистых заболеваний — 10,5%, случаи терапевтической неэффективности — 5,1%. Изложение данных о нежелательных реакциях соответствовало рекомендуемой форме в 76%. Наиболее частым дефектом заполнения являлась неполная информация о пациенте. Степень достоверности причинно-следственной связи по шкале Наранжо выставляли как определенную, вероятную и возможную. Сроки репортирования данных соблюдали в 89,1%. Для эффективного взаимодействия в системе фармаконадзора необходимо в каждой медицинской организации постоянное информирование о порядке осуществления фармаконадзора, видах нежелательных реакций, правилах их выявления и сроках репортирования данных. Курировать работу должен подготовленный специалист.

Adverse drug reactions (ADRs) are known to show sex-specific differences in occurrence and phenotype. The aim of this study was to analyse sex-specific differences in ADR-drug combinations that required hospitalization based on two different datasets.
We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR-drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR-drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis-)concordance.
In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1-2.1] for quetiapine in spontaneous reports to 41.3 [13.1-130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR-drug combination self-injurious behaviour-quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3-11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports.
Our results can contribute to raise awareness and further knowledge regarding sex-specific ADRs. The findings require further in-depth investigation.

Pharmacovigilance studies based on spontaneous reporting systems use disproportionality analysis methods to identify drug-event combinations with higher-than-expected reporting. Enhanced reporting is deemed as a proxy for a detected signal and is used to generate drug safety hypotheses, which can then be tested in pharmacoepidemiologic studies or randomized controlled trials. Higher-than-expected reporting means that the reporting rate of a drug-event combination of interest is disproportionately higher than the rate in a specific comparator or reference set. Currently, it is unclear which comparator is the most appropriate for use in pharmacovigilance. Moreover, it is also unclear how the selection of a comparator may affect the directionality of the various reporting and other biases. This paper reviews commonly used comparators chosen for signal detection studies (active comparator, class-exclusion comparator, and full data reference set). We give an overview of the advantages and disadvantages of each method based on examples from the literature. We also touch upon the challenges related to the derivation of general recommendations for the selection of comparators when mining spontaneous reports for pharmacovigilance.

OBJECTIVE: Recent case reports have suggested that sodium-glucose co-transporter 2 (SGLT2) inhibitors may interact with statins to increase their risk of myotoxicity. We assessed the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins.
METHODS: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins or both. We estimated several measures of disproportionate reporting of myopathy and rhabdomyolysis associated with concomitant use of SGLT2 inhibitors and statins: reporting odds ratio (ROR) with 95% confidence interval (CI), Ω shrinkage measure (safety signal if >0) and an extension of the proportional reporting ratio (PRR) (two-criteria set, safety signal if both criteria are met), using the full FAERS dataset as the reference set. In sensitivity analyses, we focussed on specific SGLT2 inhibitor-statin pairs with higher interaction potential (canagliflozin-rosuvastatin, empagliflozin-rosuvastatin) and accounted for stimulated reporting.
RESULTS: There were 456 myopathy and 77 rhabdomyolysis reports involving both an SGLT2 inhibitor and a statin. Concomitant use of SGLT2 inhibitors and statins was not associated with an increased risk of myopathy (ROR 0.79, 95% CI 0.70 to 0.89) or rhabdomyolysis (ROR 0.58, 95% CI 0.41 to 0.83) reporting. For both outcomes, the Ω shrinkage measure was negative and only one criterion of the PRR extension was met. SGLT2 inhibitor-statin pairs with higher interaction potential yielded potential signals for rhabdomyolysis; these signals disappeared after accounting for stimulated reporting.
CONCLUSIONS: There was no increased risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins or for specific drug pairs.

Post-marketing pharmacosurveillance is important to reduce harm to patients from marketed drugs. Oral adverse drug reactions (OADRs) are seldom reported and only few OADRs are listed scarcely in summary of product characteristics (SmPC) of drugs.
Structured search for OADRs in the Danish Medicines Agencies database from January 2009 to July 2019.
Forty-eight percent of OADRs were categorized as \"serious\" where oro-facial swelling was reported 1041 times, medication-related osteonecrosis of the jaw (MRONJ) 607 times and para- or hypoaesthesia 329 times. Four-hundred-eighty OADRs in 343 cases were related to biologic or biosimilar drugs where 73% affected the jawbone as MRONJ. Physician reported 44%, dentists 19% and citizens 10% of OADRs.
Health care professionals had a sporadic reporting pattern that seemed to be influenced by the debate in the community and in professional circles but also by the information in the SmPC of the drugs. The results indicate some reporting stimulation of OADRs in relation to Gardasil 4, Septanest, Eltroxin and MRONJ. Eventually the knowledge of OADRs increases but there is a risk of skewed information if reporting is not systematic, reliable and consistent. All healthcare professionals must be educated in spotting and reporting all suspected adverse drug reactions.

Literature reports of adverse drug events can be replicated across multiple companies, resulting in extreme duplication (defined as a majority of reports being duplicates) in the FDA Adverse Event Reporting System (FAERS) database because they can escape legacy duplicate detection algorithms routinely deployed on that data source. Literature reference field, added to in 2014, could potentially be utilized to identify replicated reports. FAERS does not enforce adherence to the Vancouver referencing convention, thus the same article may be referenced differently leading to duplication. The objective of this analysis is to determine if variations of the same literature references observed in FAERS can be resolved with text normalization and fuzzy string matching.
We normalized the literature references recorded in the FAERS database through the first quarter of 2021 with a rule-based algorithm so that they better conform to the Vancouver convention. Levenshtein distance was then utilized to merge sufficiently similar normalized literature references together.
Normalization of literature references increases the percentage that can be parsed into author, title, and journal from 61.74% to 93.93%. We observe that about 98% of pairs within groups do have a Levenshtein similarity of the title above the threshold. The extreme duplication ranged from 66% to 87% with a median of 72% of reports being duplicates and often involved addictovigilance scenarios.
We have shown that these normalized references can be merged via fuzzy string matching to improve enumeration of all the individual case safety reports that refer to the same article. Inclusion of the PubMed ID and adherence to the Vancouver convention could facilitate identification of duplicates in the FAERS dataset. Awareness of this phenomenon may improve disproportionality analysis, especially in areas such as addictovigilance.

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines\' selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.

The pharmacovigilance of a veterinary company may include the analysis of spontaneous reports of adverse events (AE) related to its products. The present study developed an AE classification flowchart to analyze AE notified to the customer service and pharmacovigilance department of a multinational veterinary pharmaceutical company in Brazil. The product-AE binomials using the flowchart were characterized in terms of their frequencies and subsequently, three signal detection models were used: Reporting Odds Ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker. The signals detected with the three methods were classified according to their intensity, always with the most intense signal in the first position. Among the signals detected by the three methods, the positions of each signal were summed to obtain an aggregated classification that considered the results of the three methods and allowed a serial interpretation. Among the 531 reports, 20 types of AE; 88 product-AE binomials were identified. From the total of reports, seven were signs identified by the three methods. The classification of AE following explicit criteria and the combined use of more than one signal detection method enhances spontaneous-reports-based pharmacovigilance.