Adverse drug reactions: Report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1994

Seventy-seven reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee (ADRSc) of the Australian Veterinary Association from April 1993 to December 1994 inclusive. The number of reports received/number of animals involved per species were: dogs (32/44), cats (18/31), horses (17/48), and cattle (10/21). Of these, 49 (64%) were classified as definite ADRs and 9 (12%) as probable ADRs. In 11 (14%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Eight reports were not classified because the manufacturer and the ADRSc disagreed as to the appropriate classification. Sixteen reports involved apparent hypersensitivity reactions, which resulted in death on 6 occasions. Six reports were associated with ‘off label’ use and 1 report with use of an expired product. Of the definite, probable and unclassified reports of suspect ADRs, the most frequent types of drugs involved were antimicrobial drugs (13 reports), anthelmintics (13), insecticides (11), vaccines (10), nonsteroidal anti-inflammatory preparations (5), chondroprotective agents (4), anaesthetic/sedative agents (4) and vitamin preparations (2). Single reports concerning definite, probable or unclassified ADRs to a vasodilator, a corticosteroid, a local anaesthetic and a disinfectant were received.     

Adverse drug reactions: Report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992

Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved veterinarians inadvertently overdosing animals. Eighteen reports involved apparent hypersensitivity reactions and 6 reports involved probable drug interactions. Four reports involved the use of drugs at appropriate doses but in inappropriate clinical situations, and 3 reports were associated with 'off-label' use.     

Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.     

Drug hypersensitivity reactions targeting the skin in dogs and cats

Adverse drug reactions (ADRs) can be dose dependent or idiosyncratic. Most idiosyncratic reactions are believed to be immune-mediated; such drug hypersensitivities and allergies are unpredictable. Cutaneous reactions are the most common presentation of drug allergies. In veterinary medicine it can be difficult to assess the true prevalence of adverse drug reactions, although reports available suggest that they occur quite commonly. There are multiple theories that attempt to explain how drug allergies occur, because the pathogenesis is not yet well understood. These include the (pro)-hapten hypothesis, the Danger Theory, the pi concept, and the viral reactivation theory. Cutaneous drug allergies in veterinary medicine can have a variety of clinical manifestations, ranging from pruritus to often fatal toxic epidermal necrolysis. Diagnosis can be challenging, as the reactions are highly pleomorphic and may be mistaken for other dermatologic diseases. One must rely heavily on history and physical examination to rule out other possibilities. Dechallenge of the drug, histopathology, and other diagnostic tests can help to confirm the diagnosis. New diagnostic tools are beginning to be used, such as antibody or cellular testing, and may be used more in the future. There is much yet to learn about drug allergies, which makes future research vitally important. Treatment of drug allergies involves supportive care, and additional treatments, such as immunosuppressive medications, depend on the manifestation of the disease. Of utmost importance is to avoid the use of the incriminating drug in future treatment of the patient, as subsequent reactions can be worse, and ultimately can prove fatal.     

Adverse reactions to veterinary drugs reported in Sweden during 1991–1995

The present article gives a summary of suspected adverse reactions reported by Swedish veterinarians during the period 1991–1995. The summary shows that severe adverse drug-reactions sometimes occur in Swedish veterinary practice. In horses, several cases of acute reactions in animals treated with procaine benzylpenicillin were reported and seven horses died within a few minutes after intramuscular injections of the drug. In cattle and swine most reports referred to the use of antimicrobial agents. In dogs reactions to vaccines were the most frequently reported adverse effects. The reactions were, however, usually rather mild. In dogs there were also several reports of severe reactions related to treatments with non-steroid anti-inflammatory drugs (NSAID) and α₂-receptor agonists. Amongst the reports six deaths were observed for each of these groups of drugs. In cats, as in dogs, adverse effects to vaccines were the most frequently reported reactions.     

Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2010

In 2010, we observed again an increase in the number of declarations reported to the vigilance system for veterinary medicinal products up to a total of 160. The species and drug classes reported remained the same as in previous years: the majority of adverse drug reactions (ADRs) concerned either dogs or cats and the most frequently involved drugs were either antiparasitic products or antiinfectives. Adverse reactions following reconversions and 8 cases of suspected allergic reactions following the use of amoxicillin-clavulanic acid combinations in dogs were reported. Additional enquiries were processed by the Swiss Toxicological Information Centre and transmitted to Swiss medic. 11 of these reported accidental ingestions of flavoured tablets in overdose by dogs and some cats. The vaccino vigilance program received 179 declarations following immunization against blue tongue disease as well as 82 declarations following the application of other vaccines. The vigilance system increases the chance to identify rare reactions or interactions and thereby contributes to the security of veterinary medicinal products.     

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2004 - February 2006)

The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2004 to February 2006 is presented. A total of 21 reports was received in the 2-year period, continuing the decline in the number of reports to a lower figure than in any previous year. This is surprising considering the legal obligation of the veterinary professionals to report all adverse drug reactions. Once again the majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were stock remedies. Veterinarians predominantly administered these products.     

Drug distribution and stability in extemporaneous preparations of meloxicam and carprofen after dilution and suspension at two storage temperatures

OBJECTIVE: To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days. DESIGN: Prospective study. SAMPLE POPULATION: Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively. PROCEDURES: Preparations were stored at approximately 4 degrees C (39.2 degrees F) or 22 degrees C (71.6 degrees F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated. RESULTS: In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained > or = 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 +/- 0.04 and 0.21 +/- 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22 degrees C for 28 days yielded bacterial growth. CONCLUSIONS AND CLINICAL RELEVANCE: DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.     

How to respond to adverse drug reactions.

Adverse drug reactions (ADRs) are part of the risks, professional responsibilities, and liabilities inherent to veterinary medicine. The incidence of proven ADRs is not known, but veterinarians should anticipate, plan, and practice a response for patients that experience adverse reactions. The attending veterinarian should work closely with professional services personnel at pharmaceutical manufacturers to provide care for those patients, to investigate causes of ADRs, and to factually improve reports of ADRs that can be of considerable medicolegal benefit to the client and the profession.     

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2002 - February 2003)

The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2002 to February 2003 is given. In total, 40 reports were received. This had declined from the previous year. Most reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were Stock Remedies. The animal owner predominantly administered these products. Only 1 report was received from a veterinary pharmaceutical company. Increasing numbers of reports are being received from veterinarians.     

Pharmacovigilance in veterinary medicine in Chile: a pilot study

Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study. J. vet. Pharmacol. Therap. 34 , 108–115. In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6‐month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under‐reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs’ presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus, Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR‐presenting drug detection and drug safety improvement.     

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2001 - February 2002)

An overview of reports of suspected adverse drug reactions received by the Veterinary Pharmacovigilance and Medicines Information Centre during the period March 2001 to February 2002 is given. A total of 77 reports were received. The majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most products implicated in the reports were Stock Remedies. The products were predominantly administered either by veterinarians or trained paraveterinary professionals. Although the majority of reports were received from veterinary pharmaceutical companies, the proportion of reports received directly from veterinarians increased compared with previous years.     

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2003 - February 2004)

The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2003 to February 2004 is given. A total of 20 reports was received. This had declined from the previous year. The general apathy with regards to the reporting of adverse drug reaction has prompted the Medicines Control Council to make reporting a legal obligation on all members of the veterinary and medical profession as from August 2004. The majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were Stock Remedies. Veterinarians predominantly administered these products. Only two reports were received from a veterinary pharmaceutical company.     

Suspected adverse reactions to veterinary drugs reported in South Africa (January 1998 - February 2001)

The Veterinary Pharmacovigilance Centre received 59 reports of suspected adverse drug reactions during the period January 1998 - February 2001. The number of reports received increased after the establishment of a formal procedure for recording and responding to reports. The number of reports received per species was: dogs 19, cats 15, cattle 7, sheep/ goats 6, chickens 4, pigs 3, horses 2 and giraffe 1. Many different types of adverse reactions were reported, including lack of efficacy, hypersensitivity, inappropriate use of products by non-veterinarians, known adverse effects and adverse effects encountered with extra-label use of products.     

Suspected adverse drug reactions in 2004

We received 62 reports of suspected adverse events (SARs) for the year 2004. Their number and repartition according to affected animals and active substances were comparable with the previous year. The distributors or manufacturers submitted most of the declarations, but the proportion submitted by practicing veterinarians is slowly growing. 72% of the declarations dealt with adverse reactions in small animals (cats and dogs), followed by cattle and horses. Antiparasitics, anti-inflammatory drugs and immunologicals were the most frequently mentioned therapeutic classes, which are listed here according to the international ATCvet classification. A report from abroad about a fatality following injection of an antibiotic preparation for cattle prompted Swissmedic to review the security of this medication also sold on the Swiss market. It was decided to modify the package insert to warn about the danger of inadvertent self-injection in humans, to reduce the risk of similar accidents in Switzerland. We hope that the pharmacovigilance system will enjoy an increasing awareness by the practicing veterinarians.     

Cutaneous and ocular adverse reactions in a dog following meloxicam administration

The present report addresses the development of cutaneous and ocular reactions possibly related to meloxicam administration in a dog. Based on clinical signs and absence of laboratory data compatible with the other differential diagnoses considered, the possibility of an adverse drug reaction (ADR) due to meloxicam was considered. Skin biopsy revealed haemorrhage of the superficial and deep dermis, associated with hyperplasia of endothelial cells and epidermal sloughing. Vasculitis in the deep dermis was also noted. Such lesions were considered compatible with an ADR. Although the owner was not aware of any previous allergic reaction to drugs, the animal had a clinical history of atopic dermatitis. Meloxicam is a nonsteroid anti-inflammatory drug (NSAID) in the oxicam family, indicated for the control of inflammation and pain in acute and chronic musculoskeletal disorders in dogs. Although meloxicam is usually well tolerated, the present clinical case represents an alert to practitioners about the potential role of NSAIDS in ADRs in dogs with a history of allergic cutaneous diseases.     

Survey of Toxoplasma antibodies among sheep in western United States

A survey was conducted to determine the prevalence of toxoplasma antibodies among breeding ewes and among lambs slaughtered for food in western United States. Each serum was tested by the indirect hemaglutination method, using microtiter technique. Agglutination (greater than or equal to 2 +) at the 1:64 dilution was considered to be a positive reaction. Of 2,164 ewes from 18 flocks tested in California, 523 (24%) were seropositive for Toxoplasma gondii, with prevalence rates among flocks ranging from 4 to 51%. In 9 of those flocks, 1,495 ewes were stratified by whether ewes had lambed or were barren. On an overall basis, the antibody prevalence was similar (about 25%) in both groups, but there was a significant difference (P less than 0.05) in 1 flock in which 30% of the nursing ewes were seropositive, compared with 21% of the barren ewes. Of 1,056 market lambs from 19 lots tested, 85 (8%) were seropositive. The antibody prevalence in lambs tested at slaughter in California, by state of origin, were: Oregon, 11/51 (22%); Nevada, 32/159 (20%); Idaho, 12/147 (5%), and California, 30/699 (4%).     

前噬菌体对猪链球菌毒力、环境适应性、耐药性及代谢活动的影响

旨在了解和掌握前噬菌体与猪链球菌(Streptococcus suis,SS)毒力、环境适应性、耐药性及代谢活动之间的关系,本研究对前噬菌体阳性菌株(简称阳性菌)与前噬菌体阴性菌株(简称阴性菌)进行了致病性试验、LD50的测定、组织荷菌数的测定及病理组织学观察、生物被膜(BF)形成能力的测定、药敏试验和转录组测序.结果...     

The ischiorectal fossa: an alternative route for the administration of prostaglandin in cattle

Three experiments were conducted to investigate the ischiorectal fossa (IRF) as a route for the administration of prostaglandin F2 alpha (dinoprost) in cattle. In Experiment 1, 21 nonlactating Holstein cows were given 100 micrograms of gonadotropin releasing hormone (GnRH), intramuscularly (i.m.), and, 7 d later, 25 mg of dinoprost into the IRF. Sixteen cows had serum progesterone concentrations > or = 1.0 ng/mL at the time of dinoprost treatment, and all of these had rapid and complete luteolysis; the other 5 cows were not considered to have a functional corpus luteum (CL) at the time of treatment. There were minimal adverse behavioral reactions to the IRF injections and no visible or palpable tissue reactions at the injection site. In Experiment 2, 74 Holstein heifers were given 25 mg of dinoprost by IRF injection. Luteolysis occurred in 84.3% of the heifers with a functional CL (as determined by the serum progesterone concentration at the time of treatment). Of the heifers bred by either natural service or artificial insemination, 61.8% became pregnant. In Experiment 3, 48 beef heifers received dinoprost 7 d after ovulation, as follows: 25 mg, i.m. (n = 9); 25 mg, IRF (n = 10); 10 mg, IRF (n = 10); 10 mg, subcutaneously (s.c.) (n = 10); or 10 mg, intravulvosubmucosally (IVSM) (n = 9). Fewer heifers (P < 0.05) were found to be in estrus or ovulating in the 10 mg IVSM group (0% and 11%, respectively) than in the 25 mg i.m. group (100% and 100%), the 25 mg IRF group (90% and 100%, respectively), or the 10 mg IRF group (80% and 80%). The rates of estrus (50%) and ovulation (50%) were intermediate in the 10 mg s.c. group. In summary, 25 mg of dinoprost injected into the IRF caused minimal behavioral or tissue response and induced luteolysis and fertile estrus. In addition, 10 mg of dinoprost injected into the IRF was as efficacious as 25 mg given either i.m. or into the IRF in inducing estrus and ovulation.     

Bone marrow necrosis in dogs: 34 cases (1996-2004)

OBJECTIVE: To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs. DESIGN: Retrospective study. ANIMALS: 34 client-owned dogs. PROCEDURES: Reports of cytologic examinations of bone marrow specimens performed between 1996 and 2004 were reviewed. All reports that indicated the presence of necrosis, stromal disruption, phagocytic macrophages, individual cell necrosis, or myelofibrosis were evaluated further. RESULTS: Of 609 reports of bone marrow evaluations performed during the study period, 34 (5.6%) had evidence of bone marrow necrosis. Nine dogs had no evidence of associated diseases or drug or toxin exposure, and 25 dogs had associated disease conditions or drug exposures. All 9 dogs with idiopathic bone marrow necrosis were anemic (mean Hct, 14%), but only 3 had neutropenia, and 3 had thrombocytopenia. All 9 had myelofibrosis. Of the 25 dogs with associated disease conditions or drug exposures, only 14 (56%) had anemia (mean Hct, 33%). In addition, 14 (56%) had neutropenia and 18 (72%) had thrombocytopenia. Only 10 (40%) had myelofibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that bone marrow necrosis may be common in dogs with hematologic disorders. In most dogs, bone marrow necrosis was associated with an underlying disease condition or drug exposure, but idiopathic bone marrow necrosis was also identified. Disease conditions that should increase suspicion of possible bone marrow necrosis include sepsis, lymphosarcoma, and systemic lupus erythematosus; drug exposures that should increase suspicion of possible bone marrow necrosis include chemotherapeutic agents, phenobarbital, carprofen, metronidazole, and mitotane.