Adverse Experiences Reporting Program - Report 1996

Introduction

Adverse Experiences Classified as Product Related or Possibly Product Related

REFERENCES

Appendix A

CATS

Parasiticides:

Vaccines:

Anaesthetic agents:

Antimicrobials:

CATTLE

Antimicrobials:

Parasiticides:

Vaccines:

Multivitamin injections:

Corticosteroids:

Mineral supplement:

Intrauterine preparation:

DOGS

Vaccines:

Antimicrobials:

Internal parasiticides:

External Parasiticides

Antiarthritic agent:

Sedatives:

Analgesics

Anaesthetics

Skin creams

Food Supplement

HORSES

Antimicrobials - parenteral:

Antimicrobials - supplements:

Parasiticides:

Local anaesthetics:

Anti-inflammatory agents:

Corticosteroid:

Topical wart treatment:

RABBITS

Rabbit calicivirus vaccine:

SHEEP

HUMAN REACTIONS

CATS

CATS contd.

CATS contd.

CATS contd.

CATTLE

CATTLE contd.

Adverse Experiences Reporting Program Report 1996

Introduction
Adverse Experiences Classified as Product Related or Possibly Product Related
CATS
CATTLE
DOGS
HORSES
RABBITS
SHEEP
HUMAN REACTIONS
REFERENCES
Appendix A
CATS
CATTLE
DOGS
HORSES

The NRA's Adverse Experience Reporting Program was established in January 1995. Voluntary reports of adverse experiences with veterinary chemical products are received by the NRA from veterinarians, farmers, and other users of such products. These reports are forwarded to product manufacturers for investigation and comment.

In its assessment of reports, the NRA considers - in addition to the information received in the initial report - the findings of the investigation by the registrant, the available scientific literature, published information from monitoring agencies in other countries, and the opinions of experienced veterinary practitioners.

On the basis of all the available information, the reported adverse experiences are then classified by the NRA as one of the following:

Product related: there is sufficient evidence to confirm that the adverse reaction, whether expected or unexpected, is related to the use of the product. Included in this group are those reactions where it is probable or almost certain that the adverse experience is related to the use of the product;
Possibly product related: it is not certain or probable that the product was responsible for the reaction but the possibility that the product was implicated cannot be excluded;
Not product related: the reaction was definitely not related to the use of the product, or there was not enough information to allow classification;
Caused by not using the product according to label directions: this category includes reactions reported after off-label use of products by veterinarians exercising their professional right to prescribe an appropriate treatment, as well as instances of overdose or incorrect route of administration.

The following report is divided into four sections. The first shows the numbers of reports received where reactions were classified as product related or possibly product related for each species and product category and the numbers of animals involved. It is presented in the form of tables 1-7 arranged alphabetically by species. A brief discussion of the adverse experiences, by product categories, follows each species table. A summary of adverse experiences in humans is given in table 8.

Thre are three appendices: Appendix A is a summary table with details of all individual reports of adverse animal reactions classified as product related or possibly product related since publication of the 1995 report. The table is divided into sections which show, for each of the products identified by active constituent, the numbers of animals involved, a brief description of each adverse reaction and the NRA classification of the reaction.

Appendix B summarises all reports of alleged lack of efficacy received in the 1995 and 1996 reporting periods, while Appendix C is a summary table of reported human reactions to veterinary chemicals.

Reactions to parasiticides made up the largest group of adverse experiences in cats.

A broad spectrum anthelmintic containing praziquantel, febantel and pyrantel embonate was the subject of four reports with the main symptoms being ataxia, vomiting, weakness and depression. The incidence of this effect remains low relative to the number of doses sold.

An eight week old kitten died 5 hours after administration of a piperazine citrate syrup. Initial symptoms of ataxia, vomiting and depression, seen within 45 minutes of treatment, were followed by bradycardia, continuing depression and coma. Batch testing of the product showed conformity with specifications except for a slightly lower potency. While the dose given in this case was normal, large oral doses are reported as causing such symptoms in dogs and cats.¹

It is well known that some cats react adversely to the pyrethrins. Products containing pyrethrins were implicated in three reports. A cat bathed by a veterinarian in a clinic, with a pyrethrin product as treatment for fleas, died at home after suffering a reaction described by the veterinarian as anaphylactic. Of two other cats washed in a veterinary clinic, one, which had an existing grade 3 heart murmur with no clinical signs, presented six hours later with seizures, dyspnoea and an elevated temperature. It died 48 hours later. Although atypical as regards time of onset, the reaction was classified as product related.

In another case, three cats were reported as adversely affected after misuse of a pyrethrin product registered for dogs. Symptoms occurred 7-10 days after washing. Diarrhoea was seen initially, followed by vomiting and seizures. One cat died after being washed with the product weekly for 5 weeks. Another cat died approximately 4-5 weeks after being washed once with the product. It is possible that the symptoms were related to the product but equally likely, because of the time involved, that other causes of disease could be implicated.

Excitement, apparent abdominal discomfort, salivation and vomiting appeared in a cat one and a half hours after treatment with a product containing levamisole and niclosamide. Levamisole toxicity can mimic OP poisoning and it was most likely that the cat was sensitive to the levamisole component.

A cat developed blisters on the lips the same day as treatment with a flea spray product containing fipronil. The veterinary nurse who assisted in application of the product developed lip blisters the next day. The registrant reported that some animals have developed localised type hypersensitivity after spraying with the product, with evidence of hyperaemia, pruritis and pin point blisters like sunburn. This reaction was classified as product related.

There were two reports of reactions in cats to a leukaemia virus vaccine. In the first case, vomiting, dyspnoea and listlessness were seen 2 hours after vaccination in the morning. By afternoon the face and ears were swollen and hot with venous congestion. The cat was depressed for 4 days. Another cat became lame in the left foreleg after a second vaccination in the left shoulder area with the product. It lost interest in food and became depressed by that evening. The next day, veterinary examination revealed a temperature of 39.4⁰C, and a mild swelling over the vaccination site accompanied by pain on palpation or extension of the shoulder. The manufacturer advised that other reactions have been reported from the batch implicated in this second report. Sterility and endotoxins levels in the vaccine have been reassessed and found satisfactory. Suitable quality controls are in place. Further testing is being conducted.

A product containing alphaxalone acetate and alphadalone acetate was the subject of three reports involving four reactions and three deaths. In two reports, cats had been premedicated with xylazine 15-20 minutes before I/V administration of the product. In both cases the reaction occurred within 3 minutes of induction of anaesthesia: in the first, cessation of respiration and in the second, cardiac arrest. No other symptoms were observed. Intra-cardiac adrenaline revived the second cat but not the first, which had been anaesthetised for repair of a minor head wound.

The third report involved two cats premedicated with acepromazine, atropine and antihistamine half an hour before the anaesthetic agent was given i/v. Cardiac arrest and sudden death occurred in one cat immediately after the full dose of the anaesthetic was administered. The other cat was found to be dead fifteen minutes after administration. No other symptoms were observed and no post mortems were carried out.

All general anaesthetics are associated with a certain level of risk. A polyoxyethylated castor oil is the vehicle or carrier substance for the active constituents in this product. This may liberate mast cell histamine in the cat and induce arterial hypotension. Allergic reactions such as hyperaemia of ears and peripheral oedema are commonly seen in cats. Anaphylactoid reactions may also be responsible for some of the deaths observed.² Respiratory failure after use of anaesthetics containing alphaxalone acetate and alphadalone acetate has also resulted in death. In the cases of the cat with the head wound, the contribution of this injury to the death of the cat is unknown.

Oral clindamycin hydrochloride given for one week to kittens of eight weeks of age was reported as causing an ulcer on the tongue of each of three kittens. No similar reactions have been reported. It is possible that the ulcer was caused by administration of the product but coincidental viral infection should also be considered as a cause.

					Type of reaction
Product Category	No. of Reports Received	No. Treated	No. Affected	No. Died	Product Related	Possibly Product Related
Parenteral Antimicrobials	14	19	18	9	17	1
Ecto-parasiticidesTopical	5	244	184	15	183	1
Intramammary Antimicrobials	3	177	97		97
Ecto-parasiticides/AnthelminticTopical	2	25	5			5
Vitamin supplements	2	31	3	1	3
Corticosteroid	2	57	2	1	2
AnthelminticOral	1	33	33			33
Vaccine	1	8	4		4
Mineral supplement	1	235	9			9
Intra-uterine preparation	1	1	1			1

Pareneteral oxytetracyclines were the subject of 9 reports, involving reactions in10 animals and 6 deaths.

Nine of the reactions were classified as product related. In another case, where oxytetracycline was given after reduction of a prolapsed uterus, it is possible that the product was responsible but other factors such as ruptured uterine blood vessels, shock, or a reaction to oxytocin could not be ruled out. Six of the 10 animals affected were males, one a calf and the rest young bulls. Three of the animals which died were bulls and three were females. One of the females was a calf.

The most common symptoms observed were facial swelling, excessive salivation and tear production, sweating, agitation, dyspnoea, ataxia and collapse. Allergic/ anaphylactoid reactions are caused by either oxytetracycline or one of the carriers such as polyvinylpyrrolidine. Rapid injections, intravenous injections, or administration to very ill or young animals are more likely to result in reactions. There are warnings on the product labels to the effect that these products may cause anaphylaxis in young cattle.

There were 5 reports of reactions to products containing procaine penicillin and benzathine penicillin. Eight cattle were affected and 3 bulls died. The time from product administration to the appearance of symptoms varied from almost immediately to 10 minutes later. Clinical manifestations of the reactions varied from almost immediate collapse to salivation, facial and vulval swelling, sweating, muscle tremors, cyanosis and ataxia. In the mildest case a bull became excited and vigorously rubbed its head on objects.

Reactions are to be expected in a small proportion of individuals undergoing treatment with penicillin. Such reactions are both uncommon and unforeseeable, and are well documented in the literature.

Intramammary antimicrobials featured in 3 reports. In the first, involving a product containing ampicillin and cloxacillin, with a withholding period of 72 hours, blue specks were seen in milk 14 days after treatment. No conclusions were reached by the manufacturer as to why this occurred. The second and third reports concerned persistent milk residues of inhibitory substances exceeding the withholding period. In the second report, where cloxacillin had been used, residues were detected in 95 out of 175 cows, six and a half days after treatment. The registrant believes it was not possible to rule out false positive tests, nor the possibility of the milking machine contributing cloxacillin to the milk for a period after treatment, as the machine was used to milk out treated cows.

In the third case, bulk milk was rejected after showing a positive Delvotest P microbiological test. This bulk milk contained the milk of a cow previously treated with a product contained neomycin sulfate, novobiocin and dihydrostreptomycin. Milk had been withheld for 6 milkings as required by label instructions. Milk samples had been discarded by the lab and so no confirmatory tests could be done. The registrant expressed concerns about the lack of specificity for antibiotics of the test used and the lack of any confirmatory tests.

(a) Topical ectoparasiticides

Topical ectoparasiticides were the subject of 5 reports. Three reports concerned a product containing deltamethrin.

In one case, one out of 40 cows treated pushed her head into a corner and was reluctant to move, walked only in straight lines and salivated profusely. The reaction was possibly connected to use of the product but this type of reaction has not been previously reported. Given reports of skin irriation with this product, it is possible that local eye irritation caused the problem.

In a second case, classified as product related, most of 147 cows treated showed general agitation and excessive tail swinging in apparent efforts to reach their backs. Milk production fell. These signs were interpreted as indicating irritation of the skin on the backline where the product had been applied 12 hours previously. A similar report of skin sensitivity and loss of production in a dairy herd was presented in the NRA's Report of Adverse experiences, 1995.

In the third case involving deltamethrin a calf suffered a minor "scald" on the white part of its back 3 days after treatment. This later developed into a larger lesion. It also began scouring and had an elevated temperature. This calf had been overdosed, but the reporting veterinarian reported seeing similar cases in other white calves.

Nine cattle died out of 29 treated with a diazinon product, where the container had been opened some time previously and the product was past the expiry date. The reactions occurred within half an hour of application with signs including respiratory distress, weakness, shaking, ataxia and drooling. Eight died within 3 hours of application and one later.

The field sample of the product had the typical orange-red colour seen in previous cases reported to the NRA in 1995. Analysis of the sample showed no diazinon remaining and although the sample was not analysed for them, toxic breakdown products were assumed to be present at a high level. The NRA concluded that this adverse reaction was due to toxic by-products produced by breakdown of diazinon following inadequate sealing of an opened container.

In a second report concerning this product 6 calves died out of 7 treated for buffalo fly control. This appeared to be a clear case of misuse of a product well past its expiry date. The container was rusty and possibly 8 years old. No expiry date or batch number was visible. Comments made by the users suggest that the dose rate was well in excess of label instructions. The manufacturer has withdrawn the product from the market because of stability problems with that formulation.

(b) Topical ectoparasiticides/anthelmintics

There were two reports of reactions to a pour- on product containing moxidectin. In the first case the hair along the backline appeared to become shorter 2 months post treatment in 4 out of 24 cattle treated. There was no sign of alopecia, scabs, pustules or skin inflammation. The band may have been a normal shedding of winter coat. However, as there have been two further reports of skin reactions, one not yet classified, it is possible that the observed effect was related to use of the product. In the second reaction, also classified as possibly product related, severe ulceration of the skin occurred along the backline, from withers to the rump. No other treatment had been given concurrently. The hair on the backline was white. Lesions did not extend down the sides of the calf.

There was one report of a reaction after administration of bovine ephemeral fever vaccine and leptospirosis vaccine concurrently. Of 8 cattle vaccinated, using an ephemeral fever vaccine diluent which had undergone a colour change, four showed reactions described as anaphylactoid with signs including dyspnoea, cyanosis,

trembling, salivation, incoordination and recumbency. The reactions were clearly related to one of the vaccines but it was not possible to determine which one was responsible, or if the colour change of the diluent was significant.

Intramuscular injections of a product containing vitamins A, D₃ and E caused what were described by the reporting veterinarian as "anaphylactoid reactions" in 2 out of 30 cattle injected. In a second case involving injection of a preparation containing vitamins A, D₃, E, B₁, B₂, B₆, B₁₂, nicotinamide and d-panthenol, the cow died within 5 minutes of injection. This was classified as a product-related anaphylactic reaction.

A cow showed respiratory distress 5 minutes after intramuscular injection with dexamethasone trimethylacetate for induction of parturition. Another 47 cows treated at the same time showed no ill effects. Despite treatment with antihistamine, the cow died 10 minutes after the injection. In a second report, 9 cows were treated with this product. One showed respiratory distress within 10 minutes of injection and was successfully treated with antihistamine. Both reports were classified as product- related anaphylactic reactions. The product label insert warns that allergic and anaphylactic reactions can occur in young animals.

Two hundred and thirty five cattle in a copper deficient area were treated with copper glycinate injection subcutaneously on the neck, along with a pour-on moxidectin product and a selenium drench. Two days later some cattle had lumps on the neck and brisket while some were suffering respiratory distress with frothy emissions from the nostrils. There was no exact correlation between those with lumps and those with respiratory distress. At a later time some cattle were seen to have blood passing from the nostrils. Approximately two months later the cattle were treated with a product containing copper as sustained release particles, along with a selenium drench mixed with a fenbendazole drench. Recurrence of the respiratory symptoms occurred. Two cattle were sacrificed for laboratory post mortem examination which revealed inflammation/necrosis in the retropharyngeal area and oedema of the oesophagus and trachea. Deposits found in the pharyngeal area were not tested. Liver tests showed no evidence of copper toxicity.

It is highly unlikely that the pharyngeal lesions and respiratory distress were caused by the copper glycinate since it was given by subcutaneous injection and the only PM lesions were in the pharyngeal/ laryngeal area. This points toward the problem being caused either by drenching injury as was suggested by the pathology laboratory, or by a local reaction to something given orally. It should be noted that the only common treatment factor on the two different occasions was the selenium drench. Subsequent drenching on a third occasion with fenbendazole and selenium resulted in no adverse effects. If drenching injury was not the cause of the problem, it is possible that there was a local reaction to the batch of selenium drench used on the first two occasions.

The registrant of the selenium product had received no previous reports of adverse reactions with this product, but the owner's remaining product was not analysed to

determine if it was within specifications. In March 1997 the owner reported further reactions with similar gagging/upper respiratory symptoms after drenching with the same selenium product.

While it is likely that the lumps reported were a reaction to the initial copper injection, it was considered that the other symptoms were not related to the copper products. The pharyngeal/respiratory problems were classified as a possible reaction to the selenium drench. The NRA is awaiting a written report on the latest reactions.

A product containing a condensation product of metacresolsulfonic acid and formaldehyde was introduced into the uterus to treat pyometron with possible retained foetal membranes. The day after treatment the cow appeared "tucked up" with a rectal temperature of 40⁰C. On re-examination, the cow was found to have closed pyometron/metritis and was then treated with parenteral oxytetracycline. The cow has now dried off completely and the attending veterinarian doubts that the cow can become pregnant again.

While it is possible the product caused this reaction, such reactions have not been reported previously. Contamination of the water used for dilution of the product should also be considered. Equally likely is that an existing condition worsened, despite treatment with this product and subsequently with another product.

					Type of reaction
Product Category	No. of Reports Received	No. Treated	No. Affected	No. Died	Product Related	Possibly Product Related
Vaccines	8	8	8	1	6	2
Antimicrobials	6	7	7	1	2	5
Internal parasiticides	7	35	30	6	28	2
External parasiticides	6	8	8	1	5	3
Antiarthritic	6	19	6	1	4	2
Sedatives	2	2	2			2
Analgesics	2	2	2		1	1
Anaesthetics	2	3	3	2	2	1
Skin creams	2	2	2		2
Nutritional supplement for cattle	1	1	1	1	1

Vaccines were responsible for the largest group of reports in dogs. One death occurred following an anaphylactic reaction. On two occasions after receiving vaccinations a

puppy developed painful joints associated with fever and inappetence, diagnosed as Immune Mediated Polyarthritis.

There were five cases of allergic reactions. One dog developed a generalised urticaria, another showed reddening of the skin and generalised swellings over the body, while in the other three cases the predominant symptoms were oedema of the face and extremities, associated in one case with vomiting and defecation.

In another case coughing began the day after intra-nasal administration of a vaccine for Bordetella bronchiseptica, concurrently with another subcutaneous vaccine and an oral parasiticide. Tracheitis was diagnosed. The dog had an elevated temperature and was lethargic. This was classified as a possible reaction to the intra-nasal vaccine. The label warns that transient coughing may occur in a small percentage of dogs. The manufacturers advised that some similar reports have been received but the incidence has been extremely low. Other products may have contributed to the dog's lethargy.

Products containing trimethoprim and sulfadiazine were the subject of three reports.

In one case following post operative administration of the antibiotic, there was swelling of the ears and tail leading to skin sloughing, which required surgical correction on a number of occasions. Following each anaesthetic there was some swelling of extremities, but the attending veterinarian was of the opinion that this was of a different nature to that observed initially. This report was classified as possibly product related.

In another report, peeling of foot pads occurred approximately 3 - 4 weeks after the end of an 8 week course of the product, by oral administration, for treatment of prostatitis in a Bearded Collie. There had been no history of accident, immersion in water, or an existing disease of the feet. Despite the length of time from withdrawal of drug to appearance of symptoms, it was considered to be a possible idiosyncratic reaction to one of the components of the product.

Skin eruptions of various kinds after use of the potentiated sulfonamides are well known. Inflammation of foot pads has been reported.³ These reactions may have been similar to toxic epidermal necrolysis reported after use of these drugs in dogs⁴ and humans⁵ where one manifestation is dermo-epidermal separation, but this condition is usually associated with bulla formation and moderate to severe pain, which was not reported in this case. The registrant raised the possibility of a breed association with the Bearded Collie in the second report.

In a third report, severe pain in the shoulders, with the dog unable to stand, followed oral administration of a product containing trimethoprim and sulfadiazine. Another dog in the household also showed sudden pain over the thoracic spine 5 days after treatment. Both dogs were Bearded Collies and in both cases there was no history of previous injury. Polyarthritis has been reported after the use of potentiated sulfonamides, principally in Dobermann Pinschers⁶, but also in other breeds.⁷

An encapsulated seroma-like mass at the injection site was found 6 weeks after subcutaneous administration of procaine and benzathine penicillin. It was classified as a possible reaction to the product.

In another case an allergic reaction followed subcutaneous injection of amoxicillin trihydrate. Symptoms reported were reddened ear pinnae, and multiple welts over the abdomen, axillae and inguinal area. The reaction was classified as product-related.

A dog, given ketoprofen for inflamed tonsils six and a half hours previously, was treated with doxycycline by injection. One hour later it developed periocular oedema and became restless. By the next morning this had progressed to ataxia and then rolling. The left pupil was dilated with a poor light reflex. There was a left head tilt and dry bronchial rales over the entire thoracic field. The dog died approximately 24 hours after administration of the doxycycline product.

The registrant noted that potential side effects do not include the observed signs which were suggestive of a cerebral disorder. They thought that while there was no proof of a direct causative link between the use of the doxycycline product and the reaction, it was not possible to rule out an idiosyncratic or allergic reaction on the information available. The reaction was classified as possibly related to the use of the product.

Treatments for internal parasites were the subject of 7 reports, with 30 dogs affected. Twenty eight of the reactions were classified as product related and 2 possibly related.

Vomiting associated with hepatobiliary disease occurred after use of a product containing diethycarbamazine and cyromazine. The product was associated with lethargy, poor appetite and hair loss in another report. The NRA was also informed by the registrant of five deaths associated with severe hepatobiliary disease after use of the product. The registrant instituted a voluntary recall procedure and this product has been subject to a label change indicating that it may be used only on dogs previously treated and which showed no adverse reaction following that treatment. It may not be used on "new" dogs.

Oral fenbendazole was given to two Chihuahuas of six years and twelve weeks of age respectively, along with a combined vaccine for distemper, parvovirus, parainfluenza and Bordetella bronchiseptica. Two doses were given on consecutive days with severe diarrhoea and vomiting following each dose. The puppy began having seizures a day after the second treatment and was found to be hypoglycaemic and hypocalcaemic. The product is not registered for use in dogs in Australia and consequently the treatment was an off label use. However the product is registered for use in the UK where the registrant reports occasional incidents of vomiting and diarrhoea. The reaction was classified as possibly related to the use of the product.

A product containing ivermectin, registered for use in sheep, but not in dogs, was given to six Rough Collies. Two were presented comatose and euthanased. One dog with seizures died despite treatment. The other three dogs became hyperexcitable and

developed twitching but recovered. No advice on the correct dose rate had been sought from a veterinarian. The dose given was approximately six times that recommended for the heartworm prevention product containing ivermectin. Sensitivity of Rough Collies to ivermectin is well known.

Accidental ingestion of a parasiticide registered for use in horses led to fitting and death 3 hours after eating a piece of bread spread with the product containing morantel citrate and trichlorfon.

Two litters of 20 puppies in total, 2 weeks of age, showed distress, increased vocalisation and a depressed temperature 9-10 hours after treatment with piperazine citrate. Two puppies died. The correct dose had been given and the product was analysed and found to be within specifications. Side effects such as vomiting, diarrhoea, lack of coordination and head pressing at high doses have been reported.¹ Acute colic due to a heavy worm burden and the effect of the product on worms may have contributed to the symptoms seen.

A report involving two dogs concerned violent vomiting 3 hours after dosing with a broad spectrum anthelmintic containing praziquantel, febantel and pyrantel emboate. This is a typical reaction seen in some dogs after treatment with the product.

External parasiticides were the subject of 6 reports, with 8 dogs affected. Five of the reactions were classified as product related and 3 possibly related.

Flea collars containing diazinon were the possible causes of "lumps" which developed in two dogs after wearing the collars for a day or two. The condition improved after removal of the collars. One dog developed a moist dermatitis.

A dog exhibited signs of hyperexcitability, drooling, diarrhoea, bilateral dilation of pupils and an elevated temperature the day after it was sprayed with a parasiticide containing fipronil. It is possible that licking the coat during the day after application caused the reaction. However the dog had also received treatment the day before the spray was applied, with a parasiticide containing praziquantel and pyrantel embonate. Also, ingestion of a toxin from another source at home cannot be ruled out.

An off label use of a parasiticide with the active constituent flumethrin, registered for use in cattle, caused ataxia, salivation, vomiting and diarrhoea in one dog which responded to subsequent veterinary treatment.

Two small dogs were affected and one died 20 minutes after being sprayed with an anti flea preparation containing garlic, citronella oil and eucalyptus oil. Cyanosis, stiffness of forelimbs and convulsions preceded death. A large dog, treated with the product from the same container, demonstrated wild running behaviour thought to be due to a skin irritation. This dog had previously been treated with the same product uneventfully, from a different container. The age of the product was unknown and no analysis was possible. The owners of the dogs reported that the product had a foul smell.

Hypersensitivity to citronella has been reported in humans and cyanosis, delirium and convulsions have been reported in eucalyptus oil poisoning in humans.⁸ Euclayptus oil is well absorbed through mucous membranes. Various central nervous system, gastrointestinal and respiratory symptoms have been reported in humans following ingestion of small amounts of eucalyptus oil.⁹

In common with other essential oils such as melaleuca oil, eucalyptus oils contain monoterpenes. Those found in eucalyptus oil are the pinenes 1,4-cineole and 1,8-cineole. Melaleuca oil products deteriorate over time due to the oxidation of terpenes to the aromatic terpene p-cymine.¹⁰ It is possible that in this case a similar deterioration of terpenes might have taken place in the eucalyptus oil component of the product. This may explain the foul smell of the product reported by the users. The optimal storage condition to prevent deterioration is a cool dark environment.

Adverse reactions reported in dogs and cats after dermal exposure to melaleuca oils include ataxia, incoordination, weakness, tremors, behavioural disorders and depression.¹⁰Similar central nervous system symptoms could be expected following sufficient dermal absorption of eucalyptus oil.

In another case, a dog began salivating and became hyperexcitable ten minutes after a wash with a product containing pyrethrins, piperonyl butoxide and N-octyl bicycloheptene dicarboxamide at 1/25 normal dilution rate, mixed with a "wool wash". Symptoms seen were similar to those reported with pyrethrin toxicity.

Adverse reactions to pyrethrin products usually do not occur when the product is used according to label directions. However overdosing of a small animal is easier than overdosing a large animal because small animals have a larger body surface to body weight ratio.¹¹ The reaction was classified as product-related, despite the apparently very low concentration of the pyrethrin component. It is possible that some oral ingestion occurred or that the animal was unusually sensitive. The effect of the "wool wash" is unknown although it is possible that the ingredients of the "wool wash" enhanced absorption of the pyrethrins.

A dog treated with a shampoo containing tea tree oil, permethrin and piperonyl butoxide began trembling within 5 minutes and had a fit. It recovered over the following two days under veterinary treatment. The reaction was considered to be related to use of the product, probably the permethrin component, but as mentioned above, melaleuca oils have been associated with ataxia, incoordination, weakness, tremors and depression.¹² Cyclic terpenes, the predominant active ingredients of melaleuca oil, can enhance absorption of other chemicals and they may have enhanced absorption of the permethrin and piperonyl butoxide components of the shampoo.

The chondroprotective drug pentosan polysulfate sodium was the subject of 4 product-related and 2 possibly product-related reports.

In two cases the principal problem was vomiting after administration of the subcutaneous formulation. In one case this occurred 6-12 hours later and in the other within 20 minutes of injection. This is a side effect seen in some dogs. The product package insert will be amended to provide this information. A further side effect of mild depression and lethargy lasting up to 24 hours is sometimes seen. This was reported in two cases, with both oral and subcutaneous administration.

Two deaths were reported after use of the product. In the first case, classified as possibly related to product use, existing illness could equally have been cause of the symptoms seen. The dog had been presented with signs of fever, weight loss, abdominal discomfort and slight popliteal lymph node enlargement. Results of biochemical and haematological examination suggested possible pyometra with differential diagnoses of hyperadrenocorticism, primary hepatopathies, iron deficiency or internal haemorrhage from a hepatic tumour. The dog was euthanased and no post mortem was done.

In the second case involving death, the dog was presented 3 days after treatment with the product, suffering from anaemia and multiple subcutaneous haematomas. Biochemistry and haematology revealed an anaemia which would have been present before the product was injected. The dog died from anaemia, hypoproteinaemia and electrolyte imbalance. It is possible the reaction was related to use of the product although a pre-existing pathology of undetermined nature was present prior to the administration of the product. It is unclear whether the product contributed to the development of signs. The product should not be used if a clotting defect exists.

Another dog became ataxic within 5 minutes after a second injection of the product, collapsed with nystagmus, slow shallow respiration, slow and irregular heart beat, weak pulse, pale mucous membranes and T 37.7⁰C. The attending veterinarian thought that accidental I/V injection could have occurred.

The reaction may have been caused by the I/V administration but it may also have been a hypersensitivity reaction. Since this reaction the dog has received continuing treatment with the capsule form without side effects. The registrant reports that a condition analogous to migraine in humans sometimes occurs following the administration of the product.

Intramuscular medetomidine hydrochloride caused swelling of the tongue and respiratory arrest in one dog. Recovery followed administration of the reversing agent, antihistamine and maintenance of a clear airway until conscious. The registrant considered it to be an idiosyncratic anaphylactic reaction.

A human sedative containing propofol given intravenously was used off label as a premedication, along with acepromazine, prior to anaesthesia of a greyhound with isoflurane. After anaesthesia there was vomiting, diarrhoea with constant straining, and brick-red mucous membranes. There was also evidence of pulmonary oedema. Anaesthesia was short as surgery was found not to be necessary. While it is possible that these events were related to use of the named product, the concurrent administration of other products complicates assessment of this report.

Bloody stools resulted when the analgesic chemical, carprofen, was administered 24 hours after injection of pentosan polysulfate sodium immediately following an orthopaedic operation. The product label for the pentosan polysulfate is to be amended to warn against concurrent use with non steroidal anti inflammatory agents.

In another case, flunixin meglumide was given for back pain, daily for 3 days. On the 4th day watery blood was observed coming from the nostrils. On the 5th day the dog was found in extremis with haemorrhagic gastroenteritis. A post mortem revealed gastroenteritis and tumours in the spleen and liver. It is possible this reaction was related to the product. NSAIDS can cause gastro-intestinal ulcers and haemorrhage. The registrant has suggested that susceptibility to flunixin could have been increased by the presence of tumours which lowered the level of prostaglandin in the gut.

Two female dogs, mother and daughter, died during routine desexing operations. Both had anaesthesia induced with thiopentone sodium and maintained on halothane. During the procedure both had needed a "top up" of thiopentone which resulted in apnoea and death. The potential for apnoea after induction with short acting barbiturates is well known by practitioners.

A product containing tiletamine and zolazepam was given intramuscularly for anaesthesia prior to castration of a 6 year old Great Dane suffering from prostatic hyperplasia/metaplasia. There was a prolonged recovery time after anaesthesia and the dog went into shock 5 hours after the operation. It recovered with treatment but collapsed with signs of shock the following day. Weakness and lethargy persisted for 2 weeks.

It is possible that prolonged recovery from anaesthesia was due to the product, since this effect has been reported in veterinary literature.However it is not possible to attribute the episode of post-op. shock and continuing weakness for 2 weeks post-op. solely to the anaesthetic. It is likely that the underlying disease and the stress of surgery would have contributed to the poor recovery.

Clinical signs and clinical pathology of zinc toxicity followed ingestion of topical preparations registered for use in humans. Both products contained zinc oxide along with other ingredients and had been used to treat skin conditions.¹³

After consuming a quantity equal to at least 4 cups of a product containing monensin, a dog became uncoordinated, staggered and died. The product carries an adequate label warning of a potential fatal result if eaten by dogs or horses.

					Type of reaction
Product Category	No. of Reports Received	No. Treated	No. Affected	No. Died	Product Related	Possibly Product Related
Antimicrobials - parenteral	9	10	10	7	10
Antimicrobials - supplements	6	6	6	1	2	4
Oral parasiticides	7	9	9	2	2	7
Local anaesthetics	5	6	6	1	6
Anti -inflammatory	2	2	2	1	2
Corticosteroid	1	1	1		1
Topical wart treatment	1	1	1		1

There were 4 reactions to penicillin in horses. Anaphylactic reactions to penicillin were reported in three cases, two of which resulted in death within minutes of the injection. The third horse collapsed with respiratory distress immediately after injection with procaine penicillin but recovered within a few minutes. In the fourth report 2 horses showed central nervous system excitement after injections of procaine penicillin. Symptoms again resolved after 2-3 minutes. These reactions may have been due to acute procaine toxicity as has been reported by Chapman et al.¹⁴

Intramuscular ceftiofur was implicated in three reports, involving three deaths. In two cases the horses had been treated with another antibiotic prior to use of the ceftiofur product. Acute diarrhoea developed after treatment with the ceftiofur product. In the third report there was a rapid onset of septicaemia and diarrhoea which did not respond to treatment. Similar reactions have been recorded in the past. The product insert warns that acute febrile diarrhoea may be caused by release of bacterial endotoxins during and subsequent to treatment and/or from interruption of normal microbial populations in the gut of the horse.

Intravenous oxytetracycline produced an unusual reaction in one horse. After the first half of the dose was given the horse began striking with both front legs and showed pronounced lifting of the upper lip. This occurred again after the second half of the product was given. Immediately at the end of administration, the horse began to sweat around the muzzle and flank, collapsed, strained violently and passed faeces and urine. Over the next 24 hours the horse developed endotoxic shock, after an apparent colon displacement and was euthanased. The initial reaction during/immediately after administration was classified as product related.

Sudden onset of symptoms soon after administration of the product may indicate an unusual anaphylactic type response or a direct cardiovascular effect of oxytetracycline. Cardiovascular effects can produce sudden ataxia, shivering, dyspnoea and collapse following intravenous administration.¹⁶ The registrant reports that a review of the last 5 years records showed no similar reaction.

Another horse experienced anaphylaxis and died within one minute of an intravenous injection of a trimethoprim, sulfadiazine product. The horse trembled, collapsed, threw its head around and paddled before death. A post mortem showed no evidence that the needle had entered the carotid, thus eliminating accidental intra-arterial injection as the cause of the reaction.

There were 6 reports of adverse reactions to a product containing virginiamycin, administered to reduce the risk of lamimitis. In three reports the main symptoms were colic and constipation. In two cases classified as product-related, colic and constipation occurred, 5 and 12 days after treatment started. In the third case, classified as possibly product-related, the horse had been given 2.5 times the normal dose. By the end of that day the horse was inappetent with a mild colic, but no constipation. The registrant thought that the observed reaction was not consistent with product administration even at higher dose rates.

The registrant advises that constipation can occur during introduction of the product and recommends gradual introduction until the full dose is reached. Very dry food should be avoided at that time. Label changes will be proposed to address this problem.

A 14 year old gelding developed hind limb oedema 3 days after use of the product started. The swellings were not painful, decreased with exercise and then returned. When the product was discontinued the oedema resolved in 4 days. It is possible that the product caused the reaction but it is more likely that that it was due to an existing condition.

When the product was used in a 10 year old pony suspected of foundering, the pony became stiff in all legs and muscles. This pony had responded well to the product in a previous episode of foundering. The symptoms seen were possibly product related but were not characteristic of the known side effects and were more likely due to an existing founder than to administration of the product.

Another horse which had been treated with the product for 3 weeks developed acute febrile diarhoea and was treated for 10 days by a number of veterinarians. The horse continued to suffer from diarrhoea and slowly deteriorated. A secondary laminitis developed and the horse was euthanased. Analysis of a sample of product showed that the virginiamycin content was within specification. The registrant is of the opinion that a link between this adverse experience and the product has not been established. However, the report was classified as possibly related on the basis that prolonged use of antibiotics may have caused a change in the gut flora leading to acute diarrhoea, as has been reported in other cases.

Three cases of mouth irritation were reported after treatment with morantel citrate and trichlorfon for parasitism. Symptoms included: swollen muzzle, face or lips; hypersalivation; swelling of buccal mucosa; difficulty in swallowing; ulceration of the tongue, cheek and oropharyngeal area. These were most likely reactions to the trichlorfon component of the product and are recognised side effects in a small proportion of horses. There is a label warning of potential adverse reactions.

There were three reported reactions to a product containing moxidectin. In the first incident, 10-15 minutes after dosing, the horse began to sway on its hind limbs, and raised its upper lip. During the next 15 minutes the horse exhibited signs of mild colic and ataxia. After 45 minutes it was depressed and dragging its back feet. The registrant reports that depression and ataxia have been observed with overdose, but not for at least 3 hours after dosing. Symptoms of colic have not been a feature of overdose and in this case the dose rate was within the normal range. The reaction was classified as possibly related to the product due to the close association between the time of administration and the appearance of symptoms.

In the second case involving moxidectin, also classified as possibly product related, a veterinarian diagnosed a mild spasmodic colic the day after administration of the product.

The third report involved a mare which had been on rich feed for 5 days after relocation from dry pasture. The day after treatment with moxidectin, the mare began scouring and by the end of the day was moribund, dying the next day with evidence of profuse, bloody diarrhoea. A post mortem was performed. The pathology laboratory diagnosed colitis X. Stress of transport or a change of feed may have led to this condition. However it is possible that the product may have caused colic, leading to stress sufficient to contribute to the development of colitis X.

Adverse reactions were reported in three horses treated with a parasiticide containing oxibendazole. The first horse developed a low grade abdominal pain. The second, which had concurrent treatment with antibiotics and butazoladin, developed diarrhoea and colic. The third, a foal, developed severe colic on the day of treatment, failed to respond to treatment for colic and died the next day. In this case a post mortem and histopathogy revealed acute mild superficial gastritis, enteritis and colitis with one or two areas of focal mucosal necrosis and ulceration. A sample of product tested within specifications. All three reactions were classified as possibly related to the product.

Five reports were received of reactions to intra-articular injections of local anaesthetics in 6 horses.

Four of the reports concerning a product containing prilocaine hydrochloride were classified as product related. The injections were given in lower limb joints for lameness examinations. Further lameness, caused by a severe synovitis, generally began after a few days and persisted for up to 8 weeks. Culture and sensitivity of

synovial fluid showed no evidence of infection. One horse was euthanased due to persistent pain and poor prognosis.

The fifth report concerned a product containing mepivacaine hydrochloride given intra-articular. The horse presented with a low level lameness. A veterinarian used the product as a knee block to determine the location of the lameness. Pain was immediate and the veterinarian was unable to diagnose the location of lameness. Radiographs taken at the same time showed no chip fractures or other abnormality. It was classified as a grade 1 lameness and spelling prescribed. Pain and swelling occurred the next day, subsiding over the next week.

When the horse was observed 3 weeks later it was very lame and could not bend the knee. Veterinary examination and radiographs revealed a periosteal reaction throughout the knee. Synovial fluid samples sent for analysis indicate a non- inflammatory joint effusion.

In this case the first episode of lameness and swelling immediately after mepivacaine injection was classified as product related. It was not possible to say with certainty that the long term lameness and periosteal changes were connected to product administration. However the reporting veterinarian observed that there was no period of normality; lameness persisted and worsened after the injection.

An anaphylactic reaction occurred after intravenous injection of a product containing phenylbutazone and sodium salicylate. The reaction occurred during administration and resulted in the horse rearing and then going down with rigid extension of the legs. It was able to stand after 30 minutes. The registrant advises that 3 other cases of anaphylactic reactions have been reported over the last 5 years.

In another case a horse became excited when approximately half the dose of a ramifenazone and phenylbutazone product had been given intravenously. On completion of the injection the horse fell to the ground and thrashed about. It sustained head trauma and died. The reaction was classified as product-related and may have been due to anaphylaxis, but accidental intra-arterial injection is also a possibility.

Methylprednisolone injected into the knee joints of a horse to treat osteoarthritis resulted in swelling and local inflammation 10 days later in treated joints. The reaction was classified as product related. The registrant has had no reports of similar reactions in horses but advised that pain without swelling does occur occasionally in humans after injection with this product.

An ointment containing salicylic acid and podophyllum resin was applied to warts on the vulva of a mare. Vaseline was applied to adjacent areas. Severe blistering occurred. It began the day after application, involving the vulva, the area below the vulva and skin on the tail, with marked loss of superficial tissue requiring veterinary treatment. The reaction was clearly related to product application. Podophyllum is

considered irritant to mucous membranes but has been commonly applied to skin warts in animals. Irritation and ulcerative local reactions are the major side effects reported in humans.¹⁷The severity of this reaction points to a sensitivity on the part of the mare to one of the chemicals, probably the podophyllum component.

					Type of reaction
Product Category	No. of Reports Received	No. Treated	No. Affected	No. Died	Product Related	Possibly Product Related
Vaccines	5	51	7	1	6	1

Four reports described skin reactions at the injection site after subcutaneous administration of a rabbit calicivirus vaccine. Signs included hyperaemia, inflammation, pruritis, dermatitis, eruptions and necrosis. These were all classed as product related and thought to be idiosyncratic hypersensitivity reactions. The manufacturer advises that the oil based adjuvant used in the vaccine can lead to fibrotic reactions or to eczema lesions.

In the fifth case where a rabbit was found dead 2 hours after vaccination, a hypersensitivity reaction was suggested as the possible cause.

					Type of reaction
Product Category	No. of Reports Received	No. Treated	No. Affected	No. Died	Product Related	Possibly Product Related
Ecto- parasiticide, topical	1	200	100		100

A product containing triflumuron produced scalding and failure to grow wool where the chemical was applied over the back. The registrant has advised the NRA that some instances of backline dermal irritation have been observed following treatment with this product. The cases tend to be related to application of the product in hot weather and without adequate shade. A label statement concerning the potential for this reaction to occur is under consideration.

Product Category	No. of Reports Received	No. Affected	Product Related Reactions	Possibly Product Related Reactions	Unclassified
Topical ectoparasiticide used on sheep	3	3			3
Topical external parasiticides used on cats and dogs	3	6		2	4
Antiseptic ointment	1	2		2

Products containing alpha-cypemethrin used for treatment of ectoparasites in sheep were the subject of two reports involving humans. In one, respiratory symptoms were noticed soon after use of the product. No medical opinion was offered and no conclusion reached. The second report described skin irritation and 'vagueness' after handling sheep previously treated with a product containing alpha-cypermethrin. Written supporting information was not supplied.

One report involved the death of a farmer from pancreatitis 5 days after he treated sheep with a product for ectoparasites. While the exact identity of the product has not been established, it was considered likely by the man's family that the product used was diazinon based. The farmer had a history of using a variety of chemicals without protective clothing and with significant dermal exposure. Medical opinion was that excessive organophosphate exposure can cause pancreatitis, but opinions varied as to whether it was the cause of the pancreatitis in this case.

Two reports involved a product containing fipronil, used for flea control in dogs and cats. In the first, a veterinarian and a veterinary nurse in the same practice both suffered asthma attacks after treating a cat in the surgery with the product. The nurse also developed blisters of the lips the following day. It was considered possible that the reactions were related to use of the product. In the second case an elderly woman reported heart palpitations and weakness after treating 2 dogs and a cat with the product, one after the other. Her hands had become saturated with the product. Clinical pathology tests showed abnormal liver function. However the woman had a long medical history of cardiac and liver disease. It was not possible to determine if the product contributed to the reported illness.

After use of a parasiticide containing fenthion on a dog the owner and two other members of the household reported reactions including swelling of the lips, rash on the lips and tongue, sore throat, nausea, blurred vision and itchy skin. The product tested to specification. Such reactions have not previously been reported from use of the product.

An antiseptic ointment containing tea tree oil was reported as causing pain in the fingers of two people in one household who had applied it to the skin of a guinea pig. No medical opinion was offered. The batch retention sample tested to specification. No other reports of such reactions have been received.

1. Courtney Charles H, Robeson Edward L. In: H. Richard Adams, editor. Veterinary Pharmacology and Therapeutics. Iowa State University Press, Ames Iowa, 7th ed. 1995:887

2. Branson Keith R, Booth Nicholas H. In: H Richard Adams , editor. Veterinary Pharmacology and Therapeutics. Iowa State University Press, Ames Iowa, 7th ed. 1995:249

3. Delmage DA, Payne- Johnson CE. J Small Animal Practice 1991; 32:635-639.

4. Noli C, Koeman P, Willemese T. Veterinary Quarterly 1995; 17:123-128.

5. Rzany B, Herin, O, Mockenhaupt M, Schroder W, Goerttler E, Ring J and Schopf E. British Journal of Dermatology 1996;135: 6-11.

6. Giger U, Werner LL, Millichamp NJ, Gorman NT. Journal of the American Veterinary Medical Association 1985;186:479-484.

7. Little CJL, Carmichael S. Veterinary Record 1990;127:459-460.

8. Wade A, editor. Martindale The Extra Pharmacopoeia, 28th edition, Pharmaceutical Press, London 1982:674 -675

9. Spoerke David G, Vandenbergh Sharon A, Smolinske Susan C, Kulig Ken, Rumack Barry H. Vet Human Toxicol 1989;31:166-168.

10. Villar David, Knight Michael J, Hansen Steven R, Buck William B. Toxicity of Melaleuca Oil and Related Essential Oils Applied Topically on Dogs and Cats. Vet Human Toxicol 1994; 36:2.

11. Hansen SR, Stemme KA, Villar D, Buck W.B. Compendium on Continuing Education for the Practicing Veterinarian 1994;16:707-712.

12. Nicholson SS. Veterinary Dermatology 1995;6:139-143.

13. Inns JH. Australian Veterinary Practitioner 1995;25:118.

14. Chapman CB, Courage P, Nielsen IL, Sitaram BR, Huntington PJ. Australian Veterinary Journal 1992;69:6.

15. NRA Report of Adverse Experiences 1995.

16. Davis Lloyd E. In: Ettinger Stephen J, Feldman Edward C, editors. Textbook of Veterinary Internal Medicine, 4th edition. W.B. Saunders Company Philadelphia 1995:331

17. Budavari Susan, editor. The Merck Index, 11th edition. Merck & Co Inc., Rathway 1989:1201.

Summary of Product Related and Possibly Product Related Adverse Experience Reports 1996

(Animal Reaction Category)

The following summary sets out the details of those reports where it has been decided that the adverse experience is product related, or possibly product related. In the latter classification it could not be confirmed that the adverse experience was definitely product related but there remained the possibility that the product was implicated. Included are reported reactions involving off label use. Reports classified as not product related are not included, nor are those reports where there was not enough information to allow classification.

The table lists the animal species affected; the generic chemical/active constituent; route of administration; number of animals involved; a description of the adverse experience; the classification of the reaction and comments. In evaluating the reports the NRA also takes into consideration climatic conditions at the time of treatment, and health and management of the animal. In situations where a number of products were administered concurrently, the active constituents of all products used are named.

This summary table is intended only to provide general information about the types of reactions that veterinarians, animal owners and others have voluntarily reported to the NRA or the manufacturer after use of the product. The information in the table is not by itself a basis for determining the safety and efficacy of a given product or for comparing one product with another, nor can it be used to predict the frequency of occurrence of a reaction.

Active Constituent	Route of Administration	No. Treated	No. Reacted	No. Died	Reported Adverse Reaction	Comments
Alphaxalone, alphadalone	Intravenous	2	2	2	Premedication with s/c acepromazine maleate, atropine and antihistamine half an hour before anaesthetic for routine desexing. Sudden death and cardiac arrest in one cat immediately after full dose of anaesthetic given, while other cat was noticed to be dead 15 minutes after injection given. No other symptoms observed. No PMs carried out	PR All general anaesthetics are associated with a certain level of risk. A polyoxyethylated castor oil is the vehicle or carrier substance for the actives in this product. This may liberate mast cell histamine in the cat and induce arterial hypotension. Allergic reactions such as hyperaemia of ears and peripheral oedema are commonly seen in cats. Anaphylactoid reactions may also be responsible for some of the deaths observed. Respiratory failure after use of the product has also resulted in death
Alphaxalone, alphadalone	Intravenous	1	1	1	Premed with xylazine, 15 minutes prior to slow administration of anaesthetic to effect. Induction was smooth. Unable to intubate because cat was too small and no suitable tube available. Proceeded to prepare minor head wound for repair. Apnoea noticed after 3 minutes. No other symptoms such as swollen ears. Intra-cardiac adrenaline failed to revive. Post mortem- some froth in trachea but no significant findings	PR As above Also possible that head wound may have contributed to respiratory/cardiac failure
Alphaxalone, alphadalone	Intravenous	1	1	Nil	Xylazine premed 20 minutes prior to anaesthesia with product for teeth cleaning. Intubated and put on oxygen. No halothane at this stage. Heart was strong and then stopped within 3 minutes. No other symptoms observed. Intra-cardiac adrenaline revived cat	PR As above

Active Constituent	Route of Administration	No. Treated	No. Reacted	No. Died	Reported Adverse Reaction	Comments
Clindamycin hydrochloride	Oral	3	3	Nil	Given antibiotic for one week commencing at 8 weeks of age. One week later one ulcer was seen on tongue of each kitten, approx size 10x5 mm. Healing took place after drug was discontinued	Possibly PR Coincidental viral infection should also be considered. No similar reactions reported. Analysis of product showed it to be within specifications
Fipronil	Topical- spray	1	1	Nil	Cat developed blisters on lips the same day as treatment with the product (Vet. nurse developed lip blisters the next day; veterinarian and nurse both had asthma attacks)	PR Registrant reports that some asthmatic cats have developed signs after being sprayed, particularly in confined spaces. Some animals have developed a localised type 1 hypersensitivity after spraying with product, with evidence of hyperaemia, pruritis and pin point blisters like sunburn
Levamisole hydrochloride, niclosamide	Oral	1	1	Nil	One and a half hours after treatment with the product cat showed excitement, apparent abdominal discomfort/pain, salivation and vomiting	Poss PR Most likely the levamisole component which has caused the adverse reaction in a cat sensitive to this chemical. Symptoms of levamisole toxicity mimic OP poisoning
Piperazine citrate	Oral	1	1	1	Kitten, 8 weeks of age, became ataxic and depressed within 3/4 hour of worming. Salivation and bradycardia (HR 50-60/min) also seen. Despite treatment there was continued bradycardia and depression leading to death	PR Adverse effects are uncommon at recommended doses
Praziquantel, febantel, pyrantel embonate	Oral	1	1	Nil	Ataxia and incoordination 6 hours after treatment. Cat was weak with elevated nictitating membranes and was very quiet for 24 hours- sleeping most of the time	PR Known reaction in some cats
Praziquantel, febantel, pyrantel embonate	Oral	1	1	Nil	Hindleg ataxia for approx 18 hours. Normal next day	PR Manufacturer reports a low incidence of such reactions

Active Constituent	Route of Administration	No. Treated	No. Reacted	No. Died	Reported Adverse Reaction	Comments
Praziquantel, febantel, pyrantel embonate; Praziquantel	Oral Oral	1	1	Nil	Cat was treated with two products in the afternoon, vomited in the evening, was listless and refused food. Listlessness continued for 24 hours before recovery	PR Overdose with praziquantel, 5 times normal. Praziquantel overdose can cause emesis
Praziquantel, febantel, pyrantel embonate	Oral	1	1	Nil	Three hours after treatment cat was ataxic; shaking; prolapse of nictitating membrane and vomited. Lethargy and inappetent next day	PR Known reaction in some cats
Praziquantel, febantel, pyrantel embonate	Oral	2	2	Nil	Ataxia, salivation, vomiting, apparent hallucinations, prolapse of nictitating membrane within 3 hours of treatment	PR Known reaction in some cats
Praziquantel, febantel, pyrantel embonate	Oral	2	2	Nil	Two and a half hours after treatment simultaneous appearance of identical signs in both cats: vomiting, urination, extreme ataxia, depression and lethargy. Anorexia, depression and lethargy persisted all the next day. Appeared well 48 hours after treatment	PR As above
Purified recombinant vaccinal antigen of feline leukaemia virus	Subcutaneous	1	1	Nil	First vaccination with this product had been given 3 weeks previously with no ill effect. Owner reported cat began limping on left forelimb during evening; very quiet & not interested in food or activity by the following morning. Examination - Temp 39.4⁰C; pain on extension of shoulder and gentle palpation of left shoulder area (area of vaccination). No wounds or other incidence of trauma seen. Also mild general swelling of vaccination area	PR Registrant advises that reactions have been reported from one batch. Sterility and endotoxins have been reassessed and found satisfactory. Suitable quality controls were in place. Further testing being conducted
Purified recombinant vaccinal antigen of feline leukaemia virus	Subcutaneous	1	1	Nil	Vomiting, dyspnoea and listlessness 2 hours after morning vaccination. There was increased gastrointestinal motility; ears were hot with venous congestion. Face and eyelids were swollen by afternoon. Cat was depressed for 4 days	PR As above

Active Constituent	Route of Administration	No. Treated	No. Reacted	No. Died	Reported Adverse Reaction	Comments
Pyrethrins, piperonyl butoxide	Topical	3	3	2	Green jelly-like diarrhoea at times. This returned 4-5 days before death and was accompanied by vomiting and seizures. Appetite remained good and cats were still active until final days. Vet assessed house for possible toxins and found none. Pathology tests revealed no abnormality	The product is not registered for use on cats. The reported illness was possibly related to use of product. However other causes of disease could equally be implicated
Pyrethrins, piperonyl butoxide, N-octyl bicycloheptene dicarboximide	Topical	1	1	1	Cat bathed by veterinarian, taken home, became distressed and died. Veterinarian diagnosed anaphylactic reaction producing severe pulmonary oedema and cardiac arrest	PR
Pyrethrins, piperonyl butoxide, N-octyl bicycloheptene dicarboximide	Topical- wash	2	1	1	Cat had existing Grade 3 heart murmur with no clinical manifestations. Six hours after washed with product in veterinary clinic by nurse, cat presented with seizures, dyspnoeic, T42⁰C, elevated heart rate. Died after 48 hours despite treatment	PR Reaction atypical as regards time of onset and age of cat. Young cats are most at risk. Low incidence given volume of product sold

Active Constituent

Route of Administration

No.

Treated

No. Reacted

No. Died

Reported Adverse Reaction

Comments

Ampicillin, cloxacillin

Intramammary

Nil

Blue specks in test bucket seen 14 days after initial treatment. WHP is 72 hours

PR

Manufacturer advises that analysis of returned unused syringes, testing of dye and batch showed no abnormality. Not able to conclude why this occurred

Bovine ephemeral fever virus;

Killed cultures of leptospira interrogans, serovas hardjo and pomona

1. Subcutaneous

2. Subcutaneous

Nil

Anaphylactoid reactions observed. All reactions came from group vaccinated with BEF vaccine using a diluent which had undergone a colour change (lighter colour). Registrant of BEF vaccine subsequently revaccinated animals, including those which previously reacted, without ill effect

PR to one of vaccines administered, but unable to determine which vaccine is responsible or if diluent colour change was relevant

Type of reaction

Product Category

No. of Reports Received

No. Treated

No. Affected

No. Died

Product Related

Possibly Product Related

Parasiticides

Anaesthetics

Antimicrobials

Active Constituent

Route of Administration

No.

Treated

No. Reacted

No. Died

Reported Adverse Reaction

Comments

Cloxacillin

Intramammary

175

Nil

Persistent antibiotic residues detected in 95 out of herd of 175 cows six and a half days after treatment. Bulk sample also positive. WHP is 4 days. Basis of complaint was that WHP is inadequate

PR

However registrant believes there is insufficient evidence to be definitive about the cause of positive inhibitory substance test results: i.e. not possible to rule out false positives, nor the possibility of the milking machine contributing cloxacillin to the milk for a period after treatment as the machine was used to milk out treated cows

Condensation product of metacresolsulfonic acid and formaldehyde

Intra-uterine

Nil

Pyometron and possible retention of foetal membranes diagnosed. Cow had normal temp with open pyometron; was eating and producing milk at 19.5 l/day on her second day in the milk vat. Given one treatment with 120 ml