Recording of suspected adverse drug reaction reporting in veterinary free-text clinical narratives.

OBJECTIVES: To use text mining approaches to identify instances of suspected adverse drug reactions recorded in first opinion veterinary free-text clinical narratives, and to evaluate whether these were also reported to either the Veterinary Medicines Directorate or the relevant Marketing Authorisation holder in order to derive an estimate of the suspected adverse drug reaction (sADR) minimum under-reporting rate. To characterise sADR reports and explore whether particular features are associated with report submission. MATERIALS AND METHODS: Two regular expressions were developed to identify mentions of "adverse drug reactions" and "side effects" in the free-text clinical narratives of electronic health records contained within the Small Animal Veterinary Surveillance Network database. Consultations containing a match for the developed regular expressions were manually reviewed for inclusion and further classified to determine the suspected product, seriousness and expectedness of the event, and an indication of whether the event had been reported. The associations between event characteristics and reporting were explored using Fisher's exact tests. RESULTS: A total of 10,565 records were manually reviewed from which 827 sADRs were identified. Approximately 90% of these sADRs were not recorded as reported. Suspected adverse drug reactions that were not considered "expected" were recorded as reported more frequently than "expected" sADRs. However, clinical severity did not appear to impact on whether there was a record of reporting. CLINICAL SIGNIFICANCE: This is the first estimate of under reporting sADRs based on real world evidence from veterinary clinical records. The under-reporting rate implied by this study highlights that further interventions are required to improve reporting rate within the veterinary profession in order to support pharmacovigilance activities and improve drug safety.

DrugCentral 2023 extends human clinical data and integrates veterinary drugs.

DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and 'Target Cards' based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are on-market drugs with expired patent and exclusivity coverage, 17% are off-market, and 23% are on-market drugs with active patents and exclusivity coverage; (ii) 59% of the drugs are oral, 33% are parenteral and 18% topical, at the level of the active ingredients; (iii) only 3% of all drugs are for animal use only; however, 61% of the veterinary drugs are also approved for human use; (iv) dogs, cats and horses are by far the most represented target species for veterinary drugs; (v) the physicochemical property profile of animal drugs is very similar to that of human drugs. Use cases include azaperone, the only sedative approved for swine, and ruxolitinib, a Janus kinase inhibitor.

Adverse event classification and signal detection of data from the customer service and pharmacovigilance of a multinational veterinary pharmaceutical company.

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.

Insights into Current Veterinary Pharmaceutics for Companion Animals in Japan: A Study Based on Data from the Veterinary Drug Side Effect Database.

In veterinary medicine, various drugs are used on a daily basis. Using inappropriate medications poses health hazards to companion animals and humans; thus, assessing adverse events in veterinary medicine has great social significance but remains an untapped area of research. In this study, to promote the appropriate use of veterinary drugs and clarify common pharmaceutical issues in Japanese veterinary medicine, we analyzed information in the Veterinary Drug Side Effects Database (National Veterinary Assay Laboratory of the Ministry of Agriculture, Forestry and Fisheries, Japan). We found that the number of reports has been increasing annually, including those on high-risk drugs, molecular-targeted drugs, and antibody-based drugs. The details of the reports were similar to those from the United States, including the misadministration of veterinary drugs to humans, improper drug management, and re-administering drugs with a history of side effects. Furthermore, 46.50% of all reports mentioned the administration of one or more drugs, with the highest number of concomitant drugs being 10. In addition, 37.78% of all reports described the use of drugs in manners deviating from the intended use indicated in the package insert. Therefore, to avoid adverse events, pharmacists may have to be involved in dispensing and aseptically preparing veterinary medicines and providing drug information and medication guidance. To optimize pharmacotherapy for ill companion animals, "veterinary pharmacy" and "veterinary medicine pharmacy" must be developed in line with clinical situations in Japan, while considering knowledge from countries that are advanced in terms of veterinary medicine.

[Vaccinovigilance: Adverse reaction reports of animal vaccines in 2020]. / Vaccinovigilance: Gemeldete unerwünschte Arzneimittelwirkungen immuno­logischer Tierarzneimittel im Jahr 2020.

INTRODUCTION: The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B).

INTRODUCTION: L'objectif du système de vaccinovigilance en Suisse est l'évaluation et la classification des effets indésirables suspectés signalés en rapport à des médicaments vétérinaires immunologiques, y compris le manque présumé d'efficacité attendue. L'Institut de virologie et d'immunologie (IVI) est l'autorité compétente pour les autorisations de mise sur le marché des médicaments immunologiques vétérinaires en Suisse et est responsable du système de vaccinovigilance. En 2020, 130 déclarations d'effets indésirables ont été reçues (5% de moins par rapport à 2019). Les signalements concernaient principalement les chiens (41%) et les chats (25%) suivis des bovins (18%) et des chevaux (7%). Chez les chiens, ces annonces impliquaient principalement l'application de vaccins combinés contre la maladie de Carré, l'hépatite, la parvovirose et la parainfluenza en combinaison avec la leptospirose, chez les chats contre le coryza et la panleucopénie féline en association avec la leucose féline. Les évaluations de causalité ont été effectuées selon le système international ABON. Dans 27% des cas rapportés, les évaluations de causalité entre la vaccination et la réaction décrite ont été évaluées comme probables (ABON A), dans 44% comme possibles (ABON B).

Assessment of veterinary drug residues in food: Considerations when dealing with sub-optimal data.

The use of veterinary drugs in food-producing animals may lead to residues in animal-derived foodstuffs, potentially posing a risk to human safety. While the process of veterinary drug residue risk assessment continues to evolve as new data emerges, a recurring challenge is when sub-optimal or incomplete data are provided with the expectation of supporting a robust risk assessment. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) is comprised of international experts who routinely deal with such data challenges when performing veterinary drug residue evaluations. Recent developments in veterinary drug residue risk assessment are described, including specific consequences of sub-optimal data during the risk assessment process. When feasible, practical solutions to such challenges are also highlighted. Case examples from recent JECFA veterinary drug evaluations are provided to clearly quantify and illustrate the concepts described. The information provided is intended to facilitate the generation of improved quality data, enabling more timely and robust veterinary drug residue risk assessments.

Poultry Farms as a Potential Source of Environmental Pollution by Pharmaceuticals.

Industrial poultry breeding is associated with the need to increase productivity while maintaining low meat prices. Little is known about its impact on the environment of soil pollution by pharmaceuticals. Breeders routinely use veterinary pharmaceuticals for therapeutic and preventive purposes. The aim of this work was to determine the influence of mass breeding of hens on the soil contamination with 26 pharmaceuticals and caffeine. During two seasons-winter and summer 2019-15 soil samples were collected. Liquid extraction was used to isolate analytes from samples. Extracts were analyzed using ultra-high performance liquid chromatography coupled with tandem mass spectrometry detection (UPLC-MS/MS). The results showed the seasonal changes in pharmaceutical presence in analyzed soil samples. Ten pharmaceuticals (metoclopramide, sulphanilamide, salicic acid, metoprolol, sulphamethazine, nimesulide, carbamazepine, trimethoprim, propranolol, and paracetamol) and caffeine were determined in soil samples collected in March, and five pharmaceuticals (metoclopramide, sulphanilamide, sulphamethazine, carbamazepine, sulfanilamid) in soil samples collected in July. The highest concentrations were observed for sulphanilamide, in a range from 746.57 ± 15.61 ng/g d.w to 3518.22 ± 146.05 ng/g d.w. The level of bacterial resistance to antibiotics did not differ between samples coming from intensive breeding farm surroundings and the reference area, based on antibiotic resistance of 85 random bacterial isolates.

Bacterias Multirresistentes. Revisión del Estado Actual / No disponible

No disponible

Veterinary pharmacovigilance in sub-Sahara Africa context: a pilot study of adverse reactions to veterinary medicine in Cameroon.

BACKGROUND: Sub-Saharan African market is highly affected by counterfeit veterinary drugs. Though these counterfeit and non-compliance of drugs can induce adverse effects during their utilization, there is no monitoring system of veterinary medicines. The present pilot study was carried out in Cameroon to identify and describe suspected cases of adverse reactions to veterinary drugs in animals and / or humans as well as inefficacy of veterinary drugs. The methodology involved a descriptive cross-sectional survey of 67 actors in the veterinary medicine sector in Cameroon. RESULTS: A total of 74/120 (62%) cases of suspected adverse effects and or lack of efficacy of veterinary drugs in animals and 46 (38%) cases of adverse reactions in humans were identified. Antiparasitics were the most incriminated therapeutic class in animals (61%) and human (56%). Adverse reactions were reported in dogs (44%) and poultry (24%) while drug inefficacy was most observed in poultry (47%). According to animal health professionals, levamisole (24%) and ivermectin (16%) were identified to be responsible for the adverse effects and that the highest level of inefficacy was most frequently reported for oxytetracycline (29%). The main adverse reactions were systemic (22%), gastrointestinal (20%) and neurological (13%) disorders. CONCLUSION: The results of this study showed that misuse and circulation of poor quality as well as lack of efficacy of veterinary drugs is very common in Cameroon. Adverse reactions were observed in animals and humans. Therefore, the establishment of a national veterinary pharmacovigilance system based on solid legal bases is essential for a continuous assessment of the risks-benefits effects of veterinary drugs marketed in Cameroon.

Perceptions of Tennessee cattle producers regarding the Veterinary Feed Directive.

Since January 1, 2017, the United States Food and Drug Administration (FDA) has fully implemented the Veterinary Feed Directive (VFD) final rule aimed at facilitating the judicious use of medically important antimicrobials in food-producing animals. The objective of this study was to identify the common perceptions of Tennessee (TN) cattle producers regarding the VFD. We used a combination of focus groups and survey questionnaires to explore TN cattle producers' perceptions regarding the VFD. Preliminary findings from seven focus groups of 62 producers were used in the development of the questionnaire sent both online and in-print to rest of cattle producers in TN. The beef focus group participants perceived the VFD: to be a top-down policy; to have led to unregulated access to in-feed antimicrobials; a regulation that has limited the producers' ability to prevent disease and leading to economic losses; to negatively affect small producers; and to be affected by challenges related to prescription writing and disposal of un-used medicines. The dairy focus group participants perceived the VFD as unnecessary and burdensome, to have affected small producers, and introduced additional costs. Among the survey questionnaire respondents, 35 (15.4%) beef producers and 6 (13.6%) dairy producers respectively were not familiar at all with the VFD. Forty-eight (21.1%) beef producers and 11 (25%) dairy producers were slightly familiar with VFD. Gender was significantly associated (P = 0.02) with the beef producers' belief in the usefulness of the VFD. Similarly, for dairy producers, herd size was significantly associated (P = 0.002) with their perceptions regarding the usefulness of the VFD. The findings of this study could inform future VFD policy review processes. More awareness regarding the VFD and its benefits is needed among both beef and dairy producers in TN.

[Vaccinovigilance: Reported adverse reactions of immunological veterinary medicinal products in 2018]. / Vaccinovigilance: Gemeldete unerwünschte Wirkungen immunologischer Tierarzneimittel im Jahr 2018.

INTRODUCTION: The registration of adverse events after the use of immunological veterinary medicinal products (VMP) is the aim of the vaccinovigilance reporting system in Switzerland. Adverse events comprise suspected adverse reactions and lack of expected efficacy. Since the Institute of virology and immunology (IVI) is the competent authority for the regulation of immunological VMP in Switzerland, the reporting system is administrated by the IVI. In 2018, 162 reports concerning authorized immunological VMP were received. While most of the reports were submitted by the marketing authorization holders (79%), practicing veterinary surgeons contributed to the reporting system, too (18%). Five reports were submitted by private persons (3%). Dogs were mainly affected (43%) with several terrier breeds and chihuahuas being the most frequently reported dog breeds. Further reports were related to cats (16%), cattle (14%) and horses (14%). Recently, the numbers of reports concerning cats (+26) and horses (+23) have considerably increased after there had been clearly less reports concerning these species (11 and 5, respectively) in the previous year. Most of the reports were based on the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza with or without leptospirosis in dogs as well as cat flu and feline panleukopenia in cats. In 29.6% of the submitted cases, the causality assessment between the vaccination and the reaction described was evaluated probable.

INTRODUCTION: L'objectif du système de vaccinovigilance est d'identifier les effets indésirables pouvant survenir à la suite de l'utilisation de médicaments immunologiques pour animaux en Suisse. En plus des effets indésirables, le système couvre aussi les cas d'absence d'efficacité souhaitée. Comme l'institut de virologie et d'immunologie (IVI) est l'autorité compétente en matière des médicaments vétérinaires immunologiques, il est chargé de gérer le système d'annonces de vaccinovigilance. En 2018, 162 notifications ont été soumises concernant des médicaments vétérinaires immunologiques approuvés commercialement. Bien que la plupart des notifications aient été envoyées par les sociétés d'enregistrement (79%), les vétérinaires praticiens (18%) et les particuliers (3%) ont également contribué avec des annonces. Les effets indésirables concernaient principalement les chiens (43%), surtout les chihuahuas et les terriers. Les chiens furent suivis des chats (16%), des bovins (14%) et des chevaux (14%). Comparé aux années précédentes, il y a eu une nette augmentation des notifications concernant les chats (+26) et les chevaux (+23). La plupart des annonces concernait des vaccins combinés contre la maladie de Carré, l'hépatite, la parvovirose et la parainfluenza avec ou sans composants contre la leptospirose chez les chiens, ou des vaccins contre le coryza et la panleukopénie chez les chats. Dans 29.6% des cas, la relation entre la réaction et l'utilisation du vaccin a été jugée probable.

Comparison of international legislation and standards on veterinary drug residues in food of animal origin.

Current legislation governing monitoring of drug residues in foodstuff of animal origin is being revised at the European level. This study provides a qualitative comparison of the legislation, public and private standards in the European Union, the United States of America (USA) and the Eurasian Customs Union/Russia. We made a quantitative comparison of Maximum Residue Levels (MRLs) applied in each region for pork kidneys for tetracycline (with a focus on doxycycline), penicillin and chloramphenicol. The Customs Union generally applied lower levels than the other regions, with MRLs for tetracyclines in pig kidneys being 1200 times lower than those applied in the USA. Growing consumer interest and concern about chemicals in their food could be leveraged to support and enhance the implementation of new initiatives to improve veterinary public health. Farmers and veterinarians could help reduce findings of drug residues in meat through the judicious use of preventive actions when using veterinary medicine.

Importance of antibiotic residues in animal food.

Veterinary medicines, especially antibiotics, are among the most important components related to animal feed production. Generally, the main use of antibiotics in animals is for the treatment and prevention of diseases and growth promotion. Antibiotic usage in animals may result antibiotic residues in foodstuffs such as milk, egg and meat. These residues may cause various side effects such as transfer of antibiotic resistant bacteria to humans, immunopathological effects, allergy, mutagenicity, nephropathy (gentamicin), hepatotoxicity, reproductive disorders, bone marrow toxicity (chloramphenicol) and even carcinogenicity (sulphamethazine, oxytetracycline, furazolidone). The most important adverse effect of antibiotic residues is the transfer or antibiotic resistant bacteria to the humans due to the mobile properties of resistance. Because of these undesirable effects, it is important to regulate the use of antibiotics in food animals. The individuals and the local procedures should be aware of the problem through education by authorities. In this review, antibiotic use in the foodstuffs and their effects on the human health will be discussed.

Persistence of antibiotic resistance genes in beef cattle backgrounding environment over two years after cessation of operation.

Confined animal feeding operations can facilitate the spread of genes associated with antibiotic resistance. It is not known how cattle removal from beef cattle backgrounding operation affects the persistence of antibiotic resistance genes (ARGs) in the environment. We investigated the effect of cessation of beef cattle backgrounding operation on the persistence and distribution of ARGs in the beef cattle backgrounding environment. The study was conducted at a pasture-feedlot type beef cattle backgrounding operation which consisted of feeding and grazing areas that were separated by a fence with an access gate. Backgrounding occurred for seven years before cattle were removed from the facility. Soil samples (n = 78) from 26 georeferenced locations were collected at the baseline before cattle were removed, and then one year and two years after cattle were removed. Metagenomic DNA was extracted from the soil samples and total bacterial population (16S rRNA), total Enterococcus species and class 1 integrons (intI1), and erythromycin (ermB and ermF), sulfonamide (sul1 and sul2) and tetracycline (tetO, tetW and tetQ) resistance genes were quantified. Concentrations of total bacteria, Enterococcus spp., class 1 integrons, and ARGs were higher in the feeding area and its immediate vicinity (around the fence and the gate) followed by a gradient decline along the grazing area. Although the concentrations of total bacteria, Enterococcus spp., class 1 integrons and ARGs in the feeding area significantly decreased two years after cattle removal, their concentrations were still higher than that observed in the grazing area. Higher concentrations over two years in the feeding area when compared to the grazing area suggest a lasting effect of confined beef cattle production system on the persistence of bacteria and ARGs in the soil.

[Vigilance for veterinary medicinal products: Reports of adverse reactions in the year 2017]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2017.

INTRODUCTION: A total of 306 reports of adverse reactions to veterinary medicinal products were received during the year 2017 representing an increase of 21% compared to the previous year. The majority of these reports described reactions concerning companion animals (180 dogs and 59 cats) as well as cattle (38 reports) and horses (14 reports). Most of the reported reactions were linked to the use of antiparasitics (158 reports), hormone products (30 reports) and anti-inflammatory products (25 reports). 40 reports were generated from consultations with Tox Info Suisse in Zürich and mainly involved the excessive intake of flavoured tablets and, in some cases, the use of products under the cascade regulation (applied to another species than that authorized). Nine signals were identified from the reports, resulting in revisions of the product information in the sections addressing contra-indications or adverse reactions.

INTRODUCTION: En 2017, 306 annonces d'effets indésirables de médicaments vétérinaires ont été enregistrées, ce qui constitue une augmentation de 21% par rapport à l'année précédente. Des réactions ont principalement été rapportées chez les petits animaux (180 chiens et 59 chats), ainsi que chez les bovins (38 annonces) et les chevaux (14 annonces). Les groupes de médicaments les plus souvent concernés étaient, comme les années précédentes, les antiparasitaires (158 annonces), les préparations hormonales (30 annonces) et les anti-inflammatoires (25 annonces). Quarante cas ont été transmis par Tox Info Suisse, Zürich, qui concernaient principalement l'absorption en surdose de médicaments vétérinaires aromatisés ainsi que quelques cas de reconversions. Sur la base de l'ensemble des annonces, neuf signaux ont été identifiés qui ont conduit à l'adaptation des informations sur les produits dans les rubriques «effets secondaires indésirables¼ ou «contre-indications¼.

Therapeutic uses of metronidazole and its side effects: an update.

OBJECTIVE: Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebiasis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles, clinical trials, and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. RESULTS: Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, rosacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. CONCLUSIONS: The therapeutic use of metronidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however, its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.

Veterinary Drug Residue in Food of Animal Origin in Switzerland: A Health Concern?

Many drugs are used in livestock farming, particularly antibiotics, with almost 80% of world antibiotic production used for animals. Therefore, veterinary drugs may be present as residues in food of animal origin even if their use is fully regulated to ensure the proper use of veterinary medicinal products, to protect consumers from undesirable residues, and to ensure the supply of quality, safe and effective veterinary medicinal products to safeguard animal health. Analytical techniques for residue analysis have improved significantly with routine use of liquid chromatography coupled with tandem or high-resolution mass spectrometry. This improvement enabled specific searches for several hundred target compounds within minutes in complex matrices such as milk, eggs, honey or meat and organs after slaughter. For many years, a national residue control programme in food has been effective. The rate of non-compliant samples remains low and shows that consumers do not have to worry too much about the presence of drug residues in food of animal origin produced in Switzerland. Despite the significant reduction in antibiotic consumption observed in recent years, the resistance rate and distribution of multidrug-resistant bacteria is steadily increasing, even in countries where drug consumption has decreased significantly. Reducing antimicrobial resistance will undoubtedly be one of the most difficult food safety challenges in the coming years.