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.

Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study.

This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance(®); Virbac SA) in 10 cats with presumed allergic dermatitis. The cats initially received two sprays/100 cm(2) of skin once daily. Clinical lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm visual analog scale with grade descriptors) and owner assessments of efficacy, tolerance and ease of use (from 1=very poor to 5=excellent) were assessed every 14 days. The frequency of treatment was reduced after day 28 in cats with a >50% reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28 and two at day 42. Intention-to-treat data were analysed. The FeDESI [mean (SD): day 0, 42.2 (15.7) and day 56, 9.9 (11.7); P<0.0001] and pruritus scores [day 0, 61.2 mm (20.1) and day 56, 14.6 mm (16.1); P<0.0001] significantly decreased throughout the trial. The owner scores for tolerance [median (range): day 14, 4 (1-5) and day 56, 4 (3-5); P=0.003] and ease of administration [day 14, 3 (2-5) and day 56, 4 (2-5); P=0.02] significantly increased during the trial, but there was no significant change in efficacy scores [day 14, 4 (3-5) and day 56, 4 (2-5); P=0.5]. There were no adverse effects attributable to the HCA spray, no significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg (1.6); P=0.51] and no significant changes in haematology, biochemistry or urinalysis (n=4). Six cats required every-other-day treatment and four required daily treatment. In conclusion, HCA spray appeared to be effective and safe in these cats, although it is not licensed for use in this species.

[Clinical application of computed tomography in cattle]. / Klinische Anwendung der Computertomographiebeim Rind.

Computed tomography involves the use of x-rays to produce cross-sectional images of body regions. It provides non-overlapping, two-dimensional images of all desired planes as well as three-dimensional reconstruction of regions of interest. There are few reports on the clinical use of computed tomography in farm animals. Its use in cattle is limited by high cost, the application of off-label drugs and the need for general anaesthesia. In cattle computed tomography is indicated primarily for diseases of the head, e.g. dental diseases and otitis media, and neurological disorders. Less often it is used for diseases of the vertebrae and limbs. In valuable cattle, the results of computed tomography can be an important part of preoperative planning or be used to avoid unnecessary surgery when the prognosis is poor.

A producer survey of knowledge and practises on gastrointestinal nematode control within the Australian goat industry.

Gastrointestinal nematodes (GINs) have been identified in Australia as a major problem in goat production, with few anthelmintics registered for use in goats. Therefore, anecdotally many producers use anthelmintics that have not been registered for goats. Using unregistered products could increase selection pressure for anthelmintic resistance as well as safety and/or meat or milk chemical residues of products from treated goats. This producer survey was conducted in 2014 to establish Australian goat producer knowledge, perception and practises of GIN treatment and control. Eighty-eight producers responded to the survey. Of these respondents, 90% thought that GINs were a problem for the Australian goat industry, and 73% considered GINs had caused production losses or health impacts for their goats during the 5 years prior to the survey. With regard to anthelmintic resistance, 7% believed that anthelmintic resistance was not a problem at all, 93% acknowledged anthelmintic resistance was a problem in Australian goats herds, with 25% of these reporting their properties as being affected. The majority (81%) of respondents believed the number of anthelmintics registered for goats was inadequate for effective GIN control. Of the 85% of producers who used an anthelmintic during the survey period, 69% had used a treatment not registered for use in goats. Fifty respondents listed the anthelmintic dosage used, and 50% of those had used a dose rate greater than the recommended label dose. The average frequency of administration of anthelmintic was 2.5 times per annum. Of the 51% of respondents who listed the frequency of their treatments given during the survey period, 16% administered four or more treatments annually to the majority of their goats and 8% administered treatments on an "as needed" basis. Faecal egg count (FEC) had been performed on 72% of properties in at least one of the six years covered by the survey. These results indicated that the majority of surveyed producers use anthelmintics that are not registered for use in goats and at different dose rates to label. These practises have the potential for increasing the spread of anthelmintic resistance in the GIN populations of goats and sheep. Further, giving dose rates in excess of label recommendations could impact goat safety and/or product residues. Further research is needed to investigate these risks and evaluate more sustainable GIN control options for goat herds. In addition more effective dissemination of information is necessary for the improvement of the Australian goat industry.

Compounding and Extralabel Use of Drugs in Exotic Animal Medicine.

Extralabel drug use is the use of a Food and Drug Administration (FDA)-approved drug in a manner different from what is stipulated on the approved label. Compounding is the process of preparing a medication in a manner not indicated on the label to create a formulation specifically tailored to the needs of an individual patient. Extralabel drug use and compounding are vital aspects of safe and effective drug delivery to patients in exotic animal practice. There are few FDA-approved drugs for exotic animal species, and many approved drugs for other species are not available in suitable formulations for use in exotic animals.

Off-label use of ceftiofur in one-day chicks triggers a short-term increase of ESBL-producing E. coli in the gut.

This trial was designed to evaluate the off-label use of ceftiofur with Marek's vaccine in one-day-old broiler chicks, a prophylactic treatment that has been done in some commercial hatcheries, on the emergence of extended-spectrum beta-lactamase producing Escherichia coli (ESBL-E. coli). A total of 168 chicks (Cobb500®) were used in a completely randomized design. Birds were assigned to two treatments (Marek's vaccine plus saline vs Marek's vaccine plus ceftiofur) and six repetitions, with 14 animals each. Cloacal swabs were collected from 1 to 14 days post-hatch. The majority (86%; p<0.0001) of the ESBL-producing isolates harboring blaCTX-M and blaSHV genes originated from animals receiving the antimicrobial. None of the isolates were positive for plasmid-mediated AmpC betalactamase genes (blaACC, blaCMY-2, blaDHA, blaFOX, blaMOX and blaMIR). These findings indicate that the off-label use of ceftiofur with Marek's vaccine is associated with the short-term increase in ESBL-producing Escherichia coli in the gut of chicks.

Systematic account of animal poisonings in Germany, 2012-2015.

A systematic retrospective study on animal poisonings in Germany (wildlife excluded) between January 2012 and December 2015 was conducted. Data were collected on animal exposure calls to German poison centres, poisoning cases presenting to the University of Veterinary Medicine, Hannover Small Animal and Equine Clinics, cases involving off-label use of veterinary medicinal products reported to the Federal Office of Consumer Protection and Food Safety and toxicological submissions to the Institute of Pharmacology, Toxicology, and Pharmacy, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Munich. Descriptive statistics were used to characterise animal type, exposure reason, type and substance, year/month of exposure, case severity and outcome. An evaluation of the data and data sources was also carried out. Variation in poisoning patterns was seen. However, dogs and cats were the most frequently reported species and medicinal products, pesticides and plants were consistently implicated as top causes of poisoning. Advantages and disadvantages were associated with each data source; bias was found to be an important consideration when evaluating poisoning data. This study provided useful information on animal poisonings in Germany and highlights the need for standardised approaches for the collection, evaluation and integration of poisoning data from multiple sources.

Extemporaneous compounding in veterinary practice: a New Zealand perspective.

AIMS: The aims of this study were to explore the extent of extemporaneous compounding in veterinary centres throughout New Zealand and to determine whether pharmacists could collaborate with veterinarians to improve this service in New Zealand. METHODS: Questionnaires were sent to 200 randomly selected veterinarians in New Zealand. Semi-structured interviews were also conducted with selected participants from four animal facilities (zoos, research facilities and animal shelters) and two compounding pharmacies. RESULTS: Of the 200 veterinarian questionnaire recipients, 99 responded. Ten replies were withdrawn from the study giving a response rate of 44.5%. Of these 89, 33 (37%) compounded in their practice. Of the 33 compounding professionals, 3 (9%) compounded daily for animals under their care; 11 (34%) weekly, 18 (54%) monthly and 1 (3%) compounded yearly. Compounding was done by 29/33 (88%) veterinarians, 16/33 (48%) veterinary nurses or 6/33 (18%) others. It was carried out due to the unavailability of commercial products, or the need for dose adjustment to ease administration or improve compliance. The animals most commonly requiring veterinary compounding were dogs (21/33; 64%), cats (19/33; 58%) or cattle (15/33; 46%). Products which were commonly compounded included cyclosporin eye drops, methimazole gels and potassium bromide solutions. Issues commonly faced when compounding included unavailability of dosage forms (18/33; 55%) or appropriate ingredients (14/33; 42%), stability (12/33; 36%), time constraints (10/33; 30%) or unavailability of equipment (9/33; 27%). Reasons given for not compounding included medicines being commercially available (38/56; 68%), pharmacy compounding for those particular practices (24/56; 43%), lack of training (21/56; 38%), ingredients (16/56; 29%) or equipment (15/56; 11%). All participants who worked with a pharmacist (11/33; 33%) described this relationship as beneficial and indicated they would continue to do so in the future. CONCLUSIONS: Veterinary extemporaneous compounding exists in New Zealand. As pharmacists have extensive knowledge in formulating medications and compounding they could be of greater value to veterinarians and their patients. Educating both professions on the opportunities available to them from this collaboration could be an important step forward. CLINICAL RELEVANCE: This study provides new information regarding extemporaneous compounding for veterinary patients in New Zealand.

Extralabel use of anesthetic and analgesic compounds in cattle.

The need for drugs for sedation, anesthesia, or analgesia in cattle is relatively common in bovine practice. Because almost nothing is specifically approved for anesthesia or analgesia in cattle, the administration of most of these drugs represents extralabel drug use. The primary purpose of this article is to discuss the pharmacokinetics of the main drugs used for sedation, anesthesia, or analgesia in cattle, including information on meat and milk withdrawal where possible.

A review of analgesic compounds used in food animals in the United States.

Extralabel drug use for pain relief in the United States is regulated under the Animal Medicinal Drug Use Clarification Act. Agents that may provide analgesia in livestock include local anesthetics, nonsteroidal antiinflammatory drugs, opioids, α2-agonists, and N-methyl-d-aspartate receptor antagonists. The challenges associated with providing pain relief in food animals and the salient pharmacokinetic and pharmacodynamic features of the analgesic compounds that could potentially be used in livestock are reviewed. The potential use of novel agents such as bicarbonate, magnesium, ethanol, and gabapentin to augment analgesia is also discussed.

Rates and determinants of antimicrobial use, including extra-label, on Ontario sheep farms.

Few antimicrobials are licensed for use in sheep in Canada, and the range of indications is narrow. Treatment in an "extra-label" manner may be ineffective. In addition, potentially harmful drug residues in food-animal products and antimicrobial resistance in bacteria may be associated with extra-label drug use (ELDU). No data had been documented on drug use, specifically antimicrobial use (AMU), in Ontario sheep, although it was thought that much use was extra-label. This study investigated AMU and ELDU on 49 lamb-producing Ontario sheep farms. Data were prospectively collected over 12 months from the participating farms, and farm-level practices were ascertained with a questionnaire. Treatment-level and farm-level variables were investigated for associations with rates of AMU by means of Poisson rate regression models fit with a generalized estimating equation to control for clustering at the farm level. Antimicrobials with high mean exposure rates included chlortetracycline (in feed), penicillins, and oxytetracycline. The exposure rate in lambs was significantly lower (P < 0.01) with antimicrobial treatment of systemic signs, respiratory disease, or wound or injury than with treatment of other reported diseases or conditions; it was also significantly lower with 3 or more lambing periods per year (α = 0.05). The exposure rate in adult sheep was significantly lower with treatment of 5 of the 6 most prevalent diseases or conditions (α = 0.05) and significantly higher with producer decision to treat and producer experience of 20 y or greater. Rates of using antimicrobials not licensed for use in sheep were high, as was extra-label use of licensed antimicrobials. Diseases reportedly treated most often with antimicrobials (e.g., systemic signs, mastitis) were significantly associated with lower rates of ELDU (α = 0.05). Compared with the rates in adult sheep, the mean rate of use of nonlicensed antimicrobials was similar in the lambs, whereas the mean rate of extra-label use of licensed antimicrobials was lower among the lambs. The results are useful in determining if public health concerns about antimicrobial use in Ontario sheep are warranted and in creating drug use and licensure strategies for the Canadian sheep industry.

Treatment of animal toxicoses: a regulatory perspective.

This article focuses on the regulatory issues to consider when veterinarians are called upon to treat animal toxicoses, in particular those involving food-producing animals. The lack of Food and Drug Administration-approved drugs to treat animal toxicoses has been a long-standing problem. This article reviews extralabel drug use regulations, and the responsibilities of the treating veterinarian. It discusses the legal implications of compounding and the use of unapproved drugs to treat animal toxicoses. Efforts should be made to increase the availability of life-saving antidotal therapies.

Development of rapid immunoassays for the detection of ractopamine in swine urine.

The monoclonal antibodies (mAbs) against ractopamine (Rac) were prepared and their properties identified by indirect competitive enzyme-linked immunoabsorbant assay (ELISA). The IC(50) of mAbs was 2.7 ng ml(-1) towards Rac or 9.3 ng ml(-1) towards Rac-glucuronides and no cross-reactivity (CR) towards other competitors except dobutamine (CR: 3.76%). Based on the mAbs, the Rac-kit (kit) and Rac-strip (strip) were developed to detect Rac residues in swine urine. The strip and kit assay could be performed within 5-10 min and 2 h, respectively, allowing the analysis of urine samples without the need for sample clean-up. The detection limits were 1 ng ml(-1) for kit and 3 ng ml(-1) with the unaided eye, and 0.2 ng ml(-1) with the Strip Reader for strip. The correlation coefficients (R(2)) were 0.988 for kit in the range 0-128.0 ng ml(-1), and 0.987 for strip in the range 0-10.8 ng ml(-1). Comparing the gas chromatography-mass spectrometry (GC-MS) with the kit or strip in swine urine spiked with Rac standards, the differences ranged from 1.4% to 4.5% for kit and 1.0% to 4.7% for strip. However, the differences were greater than 54% for the kit and 55% for the strip test for the analysis of urine from swine treated with Rac. The results obtained from GC-MS using hydrolysed urine samples were generally in good agreement with those obtained from strip or kit using non-hydrolysed urine samples.