NRA Adverse Experience Reporting Program for Veterinary Chemicals

TABLE 1  CATS

Parasiticides:

The largest single group of adverse experiences in cats was associated with parasiticides. There were four reactions to a broad spectrum anthelmintic containing praziquantel, febantel and pyrantel emboate. Symptoms included ataxia, protrusion of the third eyelid, depression, severe vomiting and weakness. The incidence of this effect remains low relative to the number of doses sold. The manufacturer has included label warnings and is preparing a formulation change to overcome the problem.

As regards the pyrethrin products, it is well known that some cats react adversely to the pyrethrins. Current product labels give adequate warning to that effect, yet adverse reactions were reported in eight animals to pyrethrin based shampoos or rinses - probably due to ingestion of the product. (It should be noted that five of these reactions, including the two deaths, were in kittens of eight weeks of age, treated with a product which has a clear label warning, under the 'Contraindications' heading, that animals less than three months of age should not be treated with this product).

Whilst the number of formal reports is quite low in relation to the volume of the pryrethrin products sold they suggest that label warnings are not always clear or readily visible to users. Such warnings may need to be given more prominence, and worded in a less technical manner. This matter will be considered further by the NRA.

Vaccines:

There were five reports of reactions to vaccines. Three of these appeared to be caused by a local reaction of discomfort and the others were due to hypersensitivity. Such reactions have been reported previously in the veterinary literature and are rare but unavoidable. They occur in a very small percentage of the very large number of cats which are vaccinated yearly.

Anaesthetic agents:

Three reports involving anaesthetic agents were classified as possibly product related. In one, involving premedication with atropine and sedation with zolazepam hydrochloride and tiletamine hydrochloride, a pre-existing cardiomyopathy may have been the cause of death during surgery. In another report involving zolazepam hydrochloride and tiletamine hydrochloride, followed by halothane induced anaesthesia, a cat died 8 hours after administration. It had suffered respiratory depression and cyanosis followed by unconsciousness 20 minutes after injection with the sedative. It is possible that the reaction was related to one of the products used, but it was not possible to identify the exact cause of death.

After administration of a product containing alphaxalone acetate and alphadalone acetate a cat developed a swollen tongue post operatively, prolonged recovery time, epileptiform seizures and deterioration leading to death within 24 hours.

Sedatives and analgesics:

Sedatives and analgesics were implicated in two reports. In one, a cat was treated with pethidine subcutaneously (s/c) along with other drugs and subsequently, following seizures which appeared 15 minutes later, with more drugs including diazepam intravenously. The administration of pethidine to cats at doses in excess of 20mg/kg may result in central nervous system excitability but this reaction has not been observed at a clinical dose rate, as was given in this case. The reaction may reflect an idiosyncratic reaction, or enhanced susceptibility to the effects of pethidine in that individual animal. However this cat had already suffered a car accident and seizures and death may have simply reflected the brain damage suffered in the accident. Death may also have occurred due to apnoea as a result of the subsequent use of another CNS depressant, diazepam. This case highlights the difficulty of identifying the exact cause of an adverse reaction when a number of drugs have been used. The available information points to a possible relationship between the initial CNS excitability and the administration of pethidine.

In the other report, two young clinically healthy cats developed pulmonary oedema and mild dyspnoea 30 minutes after the intramuscular injection of medetomidine hydrochloride according to label instructions. The cats recovered with treatment. After administration with medetomidine hydrochloride there is commonly a decrease in heart rate and an initial increase in systemic blood pressure which then returns to normal or slightly below. The manufacturer reports that the number of animals suffering cardiopulmonary collapse after use of the product has been very low. Nevertheless, the label carries a warning that care should be taken when using this product in animals with existing cardiovascular or respiratory disease.

Antimicrobials:

Antimicrobial drugs were implicated in two cases involving amoxicillin and clavulanic acid. One involved an anaphylactic reaction and the other a possible exacerbation of an existing skin lesion. Given the large numbers of cats treated with antimicrobials each year this is a very small percentage of adverse reactions.

Hormones:

Diabetes was diagnosed in a cat one week after treatment with a product containing megestrol acetate. There is an adequate warning on the label stating that this drug is contraindicated in diabetes 

TABLE 2  DOGS

Vaccines:

The largest single group of adverse experiences in dogs, (seven reports, 11 dogs), involved vaccines. Of these, three were classified as product related and caused by hypersensitivity reactions. Adverse reactions to live vaccines in dogs have been described relatively frequently in the literature. Such reactions are rare but unavoidable in a small percentage of the canine population.

In a vaccine related incident affecting three dogs, the development of cellulitis at the injection site was accompanied by fever and lethargy. This reaction was possibly related to the injection, although the source of the vaccine was suspect, as was the quality of the diluent. The vaccine was administered by the owner after dilution with a multidose diluent from an open bottle.

In the other three reports classified as possibly product related, the picture was somewhat confused in the first case by the administration of two oral and two topical drugs at the same time as the vaccine, but the reaction was classified as possibly an immune based polyarthritis.

In the second report, three pups were affected and two pups died 2-3 days post vaccination after showing symptoms related to the central nervous system. However a post mortem and histopathology showed minimal evidence of cerebral changes to explain the main presenting signs. The pathologist commented that neural lesions were not suggestive of post vaccinal aberrant reactions. Given that the brains of two pups with comparable clinical histories did not contain structural changes or evidence of infection/inflammation, functional disease particularly of toxic aetiology remains strongly suspected. The NRA has classified this report as possibly related to the vaccine but notes the distinct possibility that toxins may have been responsible.

There was fever, inappetence, a reluctance to walk, mild anaemia and leucocytosis in a third case which responded rapidly to treatment with corticosteroids and antibiotics. This was possibly an immune based polyarthritis.

Antimicrobials:

Antimicrobials featured in six reports, three classified as product related, one of which was an "off-label"use and one where the product was not given according to dosage directions on the label. In the latter case trimethoprim and sulfatroxazole, administered at double the recommended dose intravenously, resulted in immediate collapse of a dog. An adequate warning is present on the label. In another case procaine and benzathine penicillin caused a local site reaction.

A death followed use of the human drug cephazolin sodium intravenously. Cephazolin belongs to the cephalosporins which are known allergenic drugs. As this drug is not registered for veterinary use, its use was 'off-label' in this instance.

In the 'possibly related' category, amoxicillin was reported as the cause of a reaction and death when given s/c and into a wound while the dog was anaesthetised. While it is  possible that a severe allergic reaction to the penicillin nucleus may have occurred, death may also have been caused by cardiac arrest from the anaesthetic agent halothane, which has a depressant effect on the cardiovascular system.

In another case amoxicillin and clavulonic acid was administered to a dog along with four other drugs. Although the reaction, masticatory myositis, is classified as possibly product related, this situation highlights the difficulties in attributing an adverse experience to one of many drugs given simultaneously and the need to assess all factors relating to the administration of the drugs.

Clindamycin hydrochloride may have caused the reaction described in a dog the day after treatment when it appeared tired, shaking and shivering. Clinical reactions to clindamycin in dogs involving nervous, respiratory and gastrointestinal signs have been reported by the FDA's Centre for Veterinary Medicine in the USA.

External parasiticides:

Treatments for external parasites were the subject of three reports, with 5 dogs affected.

Topical application of permethrin was reported as causing skin inflammation in one case. This condition was cured after treatment with an antihistamine and a corticosteroid.

Vomiting within an hour of treatment with a product containing lufenuron was classified as a product related reaction. A similar reaction was described in the Report of the AVA Adverse Drug Reaction Subcommittee, 1994. AVJ Vol. 73 No. 4, April 1996. The registrant has suggested that advice on a split dose treatment regime should be included on the label or package insert.

Topical application of a product containing pyrethrins and piperonyl butoxide applied to nine puppies was reported as causing listlessness, crying, shivering, groaning, progressive weakness and death in three of the puppies. It was not possible to say that the product definitely caused this adverse reaction and the NRA has classified it as possibly related to the product.

Anthelmintics:

Two reports involving three dogs concerned adverse experiences after the administration of a broad spectrum anthelmintic containing praziquantel, febantel and pyrantel emboate. Clinical signs began 3-6 hours after treatment and included severe vomiting, restlessness and depression. Although the incidence of this reaction is very low relative to the number of doses sold the NRA will continue to monitor such reactions to this product.

Antiarthritic agent:

Profuse salivation, vomiting, tachycardia and a weak thready pulse were reported in a dog 5-10 minutes after an injection of the chondroprotective drug pentosan polysulfate sodium. The dog recovered within an hour. The manufacturer reports that there have been isolated reports of vomiting post- injection. One case was reported to the AVA Adverse Drug Reaction Sub Committee and two were reported directly to the registrant by telephone.The manufacturer suspects that the vomiting may be due to the benzyl alcohol stabilizer.

Sedatives:

Half an hour after administration intramuscularly of a sedative dose of xylazine plus atropine sulphate to an intractable dog it became excitable with loud howling, muscle spasms, dorsiflexion of the neck and extension of forelimbs. This dog was treated with i/v diazepam and half an hour after that the dog became calm but very depressed with a temperature of 42⁰C. The reversal agent for xylazine, yohimbine hydrochloride, was given at this time as well as supportive treatment but the dog died half an hour later. It was not possible to do a post mortem.

The attending vet was of the opinion that the death was due to malignant hyperhermia. According to the label warning, the product may occasionally cause muscle tremors, bradycardia, partial atrioventricular block and reduced respiratory rate in horses.

Malignant hyperthermia has been reported in genetically susceptible pigs associated with halothane anaesthesia. It has also been reported to occur in genetically predisposed dogs following the administration of certain drugs, such as halothane and succinylcholine chloride. This is the first report in dogs of a suspected association of this condition with xylazine and atropine sulphate.

The FDA's Centre for Veterinary Medicine 1993 Annual Summary reports convulsions in one out of eight dogs which reacted adversely to xylazine and also one death in the group. Seven reactions in dogs to yohimbine showed, among other signs, fever in one dog and death in one dog. The NRA has classifed this as possibly product related as regards the use of xylazine and the initial excitement phase half an hour after administration. However in this particular case it is not possible to attribute the actual cause of death to xylazine given the other drugs used subsequently.

Tranquilizers:

A dog given acepromazine maleate orally in the upper range of normal dosage was ataxic and suffered extreme urinary incontinence 12 hours later. While an adequate label warning exists for ataxia symptoms reported after use of acepromazine maleate, the manufacturer noted that the magnitude of the urinary incontinence and the extent and duration of sedation were not expected. This appeared to be an individual reaction to the drug by the dog concerned.

Corticosteroids:

Masticatory myositis developed in a dog after oral administration of prednisolone and four other drugs concurrently. The problem appeared to resolve when the prednisolone was withdrawn. Given the number of drugs administered it is difficult to determine the exact cause of the reaction. Frequent opening of the mouth to administer the drugs may have contributed to the problem.

TABLE 3  CATTLE

Parasiticides:

There were four reports in cattle involving parasiticides (ecto-parasiticides and anthelmintics), both oral and topical. Two cattle died after use of a diazinon product, where the container had been opened some time ago and the tin was rusty. Laboratory analysis confirmed a degradation of the diazinon from 200gm/L to 1gm/L and toxic breakdown products were assumed to be present at a relatively high level. The NRA considered that this adverse reaction was due to toxic by-products produced by breakdown of diazinon following inadequate sealing of an opened container. A warning statement is present on the label drawing attention to the moisture sensitivity of diazinon and the need to keep containers tightly closed. Following more recent similar incidents the manufacturer has decided to withdraw the product from the market because of stability problems with that particular formulation.

After use of a pour-on deltamethrin product concurrently with a fenbendazole drench on 150 dairy cows, the owner reported extreme skin sensitivity in most cows and a drop in production for 3 days. The owner declined the offer of the manufacturer to carry out re-treatment with deltamentrin under supervision. A certificate of analysis of the product showed it tested to specification. The NRA classified it as a possible adverse reaction to the deltamethrin and will continue to monitor the product.

Of a group of 65 cattle treated with ivermectin as a pour- on, 12 calves died within 3-5 days of treatment and 3 cows died 6-8 days after treatment. Abnormal behaviour was observed in only one animal "hanging about the troughs" the day before being found dead. Cows and calves were fed supplements of oats and lupins, in addition to pasture and wheaten hay, and, in the case of calves, some milk replacer powder. These supplements were medicated with virginiamycin. Samples from the necropsy of three calves have been submitted for histopathological and other examination. The registrant will supply the results of this investigation when it is complete. However there have been 5 reports of adverse reactions to ivermectin involving 273 animals with 7 deaths reported in the USA to the FDA's Centre for Veterinary Medicine. The NRA has classified this as possibly product related and awaits the results of the manufacturer's investigation.

In another case 180 milking cows and 45 calves were treated with an oral anthelmintic containing levamisole hydrochloride and oxyclozanide. The milking cows began scouring within 12 hours, were off feed and there was a minor depression in milk production. There is adequate warning on the labels of the adverse reactions experienced by the cows. The calves developed intractable diarrhoea and five died the day after treatment. A post mortem was carried out on a calf. The NRA is awaiting the pathology results and registrant's comments on the reaction of the calves.

Vaccines:

There were three reports of vaccine reactions in cattle. One, possibly related to use of the product, was a report of inappetence, lethargy and swelling in the brisket region of 10 cattle after administration of bovine ephemeral fever virus vaccine.

After vaccination for leptospirosis, two out of over 40 cattle went down within one hour, experienced muscle spasms and became bloated. They responded to veterinary treatment. The temporal relationship of the onset of symptoms to the administration of the vaccine led to the conclusion that the reaction was possibly related to the product.

A booster vaccine with toxoids of clostridial species was given to 24 steers 15-18 months of age. One died the next day . The registrant reported that a post mortem revealed atypical lesions of blackleg as can be seen in vaccinated animals. It is not likely that the booster vaccination itself caused the death but rather that the beast had not responded to the overall vaccination procedure. It is recognised that no vaccine is 100% effective and in a normal population distribution, some animals may not respond. Although included in this group of animal reactions the case is more accurately described as an example of ineffectiveness.

Antimicrobials:

Acute hypersensitivity reactions were observed in three animals injected with procaine penicillin and benzathine penicillin. In one there was rapid onset of agitation, restlessness, swollen eyelids and muzzle, cyanosis, hypersalivation, and recumbency. This animal recovered uneventfully after treatment. The signs seen were those of an acute anaphylactic reaction. It is known that the penicillin nucleus is a good sensitizing agent, and that allergic reactions are to be expected in a small proportion of individuals undergoing treatment with penicillin.

In another situation in which death occurred 25 minutes after injection with a penicillin product, the animal first began rubbing its head, kicking and staggering, then became bloated with the tongue hanging out and dribbling. The cause of death could not be determined by the examination of the tissues provided for histopathology. The product was found to be satisfactory. Such reactions are both uncommon and unforeseeable, and severe anaphylactic reactions to this type of product are well documented in the literature.

In the third case involving penicillin there was ataxia for 15 minutes after treatment with the animal recovering uneventfully. This was a relatively mild adverse response which was most likely an anaphylactoid reaction due either to inadvertent intravascular administration or to sensitivity to procaine penicillin.

While hypersensitivity reactions to penicillin are well documented, the number of adverse reactions reported is small in relation to the total number of doses administered yearly. It should be noted that this product is registered for use by, or under the direction of, a registered veterinary surgeon who should know the potential for such a reaction to occur.

An 800 kg bull injected intramuscularly with oxytetracycline reacted immediately with a sudden onset of struggling, slobbering, agitation, facial and ear oedema, head shaking and coughing. Only 1/3 of the calculated dose had been given when the reaction occurred. This effect lasted for 3-5 minutes and responded to treatment with adrenaline, steroids, antihistamines and clenbuterol hydrochloride. There is a warning on the product insert to the effect that the product contains PVP povidone and may cause anaphylaxis in young cattle.

In a cow where calcium borogluconate and penicillin were administered at the same time, sudden death followed an abnormal heart rate. Death may have been due to an acute anaphylactic shock related to penicillin or to inadvertent over-dosing with the calcium preparation.

Mineral supplement:

A copper injection was given to 27 cattle, concurrently with a pour-on product containing moxidectin, a flukicide containing triclabendazole and a vaccine containing toxoids of clostridial species. Symptoms of depression, lethargy, kicking abdomen, lameness and fever in 19 cattle were seen the next day. A small trial was carried out, the results of which led a state veterinarian to the conclusion that the reaction (initially reported as caused by the moxidectin product) was related to the copper injection. Given the administration of a number of products at the same time it may be more accurate to classify this incident as a possible reaction to the copper injection.

TABLE 4  HORSES

Antimicrobials:

There were two reactions to penicillin in horses, one an anaphylactic reaction and the other local.

Intramuscular ceftiofur was implicated in four reports, involving two deaths. In one case ceftiofur was given for a severe tendon injury. The trainer also gave phenylbutazone against veterinary advice. After six days of treatment the horse started scouring and died four days later, despite hospitalization and treatment with intravenous and oral electrolytes and possibly antibiotics. The diarrhoea may have been associated with the ceftiofur but the NRA notes that the attending veterinarian was of the opinion that the problem was more stress related, compounded by further training when rest was indicated.

In the second report where a death was involved, the horse had been treated with ceftiofur for aspiration pneumonia following surgery. It subsequently developed a profuse diarrhoea and a severe pectoral myonecrosis /cellulitis of suspected clostridial origin at the injection site. When the horse was euthanased and autopsied a post mortem and laboratory report confirmed the diagnosis of "acute fulminating necrotising fibrinous typhlocolitis" and commented on the probable association with antibiotic therapy. It is likely that the pectoral lesion was caused by local contamination at the injection site and is not related to the ceftiofur per se.

In another report one horse out of three treated with ceftiofur developed diarrhoea for 3-4 days despite withdrawal of treatment.

The registrant, in reporting these reactions, referred to a paper on a diarrhoea syndrome in horses [Stewart MC, Hodgson JL, Kim H, Hutchins DR and Hodgson DR (1995), AVJ Vol. 72, No.2.]. Although the evidence is only circumstantial, antibiotic administration may have contributed to the development of acute febrile diarrhoea in these cases possibly by altering the intestinal microbial flora and thereby predisposing to acute colitis. The authors believe that the type of antibiotic used is not the critical factor and that the condition can be caused by any antibiotic used whenever the required "stress factors"are also present. The strenuous exercise of training and the associated dietary regime may predispose toward this syndrome. The condition which was referred to as acute febrile diarrhoea is a form of acute typhlocolitis in adult horses and characterised by a sudden onset of profuse diarrhoea, associated with fever and clinical evidence of dehydration, toxaemia and shock.

Veterinary literature contains a number of references to diarrhoea in horses following the use of antibiotics, where it appears to be caused by endotoxins released from bacteria at the time of treatment with the antibiotic.

There is a specific warning on company literature, including the product package insert to the effect that the administration of antibiotics to horses under stress may be associated with acute diarrhoea.

A fourth report on ceftiofur gave details of a horse treated for a respiratory infection which became distressed after the second injection and started sweating and panting, with a mildly elevated heart rate. It became feverish, developed swelling of distal limbs and joints and then recovered fully after non-steroidal anti-inflammatory therapy. This is the first time an apparent anaphylactic reaction such as this has been reported. There is a label warning that allergic reactions can occur in sensitized individuals.

Parasiticides:

Two cases of mouth irritation were reported after treatment with morantel citrate and trichlorfon for parasitism. Symptoms included not eating, drinking or suckling, teeth grinding, hypersalivation and resistance to bitting. The most likely cause is local tissue reaction to trichlorfon. This is a recognised side effect in a small proportion of horses and there is a label warning to that effect.

A horse owner reported an adverse reaction in two out of three horses treated with a parasiticide containing oxibendazole and dichlorvos. The product appeared to burn the throat of the horses immediately after administration. Signs included distress and rubbing of the neck on posts. One horse went down immediately and rubbed its neck and face on the floor while turning the lips up in apparent discomfort.

Another horse treated with this product developed what was thought to be an upper alimentary tract infection 6 days later and was treated by the owner on the advice of a veterinarian. The horse was depressed, inappetent and had mild ataxia. It was later examination by a veterinarian. Clinical pathology indicated the presence of an acute inflammatory focus and the veterinarian diagnosed an episode of acute gastroduodenal ulceration. The NRA will continue to monitor such reactions to this product.

It was suggested in the AVA Adverse Drug Reaction Subcommitte Report of 1994 that exposure of anthelmintic pastes to high temperatures often causes separation of the excipient and the drugs, leaving high concentrations of caustic drugs in a small proportion of the drench. It is not known if the products were heat affected in the cases reported to the NRA.

Anaesthetics and sedatives:

A horse previously sedated with intravenous xylazine was given intravenous ketamine 10 minutes later. Before completion of the injection the horse violently lunged into the air, falling five metres away. The operation was performed and the horse recovered from the anaesthetic. Twenty minutes after standing, marked respiratory distress and a grossly swollen throat area were observed. After about 30 minutes the horse collapsed and died. A post mortem revealed a haematoma of approximately 10 litre capacity. While it is possible that the horse might have experienced an 'idiosyncratic seizure' following the ketamine injection, such reactions are not normally experienced after adequate sedation with xylazine.

The combination of xylazine and ketamine used in this case was appropriate under the circumstances and should have produced uneventful anaesthesia. Ketamine can trigger generalized convulsions if it enters the brain tissue prior to the onset of the xylazine effects. This is possible with fast administration of ketamine as would occur with inadvertent intra-arterial administration during induction of anaesthesia. In such situations ketamine can override the muscle relaxant effect of xylazine. A similar case is described in Adverse Drug Reactions: Report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1993 in the AVJ Vol.71. No2, February 1994 convened by JE Maddison.

The NRA has recorded the incident as possibly product related to both xylazine and ketamine and will keep both products under observation.

TABLE 5  PIGS

Piglets aged from 10-18 days treated with intramuscular procaine penicillin for greasy pig disease reacted within one hour. All vomited, producing yellow pasty vomitus. Some had diarrhoea and weakness. All recovered within six hours. The label for the product carries a warning of such reactions in piglets.

TABLE 6  ALPACAS

A product containing moxidectin given subcutaneously to 60 alpacas produced severe pulmonary oedema, 3-5 minutes post injection in one animal with white froth passed from the nose and mouth. This animal recovered gradually with treatment. The signs observed were consistent with acute anaphylaxis which may occur sporadically with any injectable product. Such a reaction is an infrequent and unpredictable occurrence.

TABLE 7  BIRDS

In the report involving use of pyrethrins on birds it is considered that the birds' faces may have been inadvertently sprayed, despite adequate warning on the label

TABLE 8  HUMANS

Products containing diazinon and cyromazine used concurrently for ectoparasite control in sheep caused a variety of symptoms including headaches, nausea, vomiting and rashes in four shearers via skin contact with, and possible vapour inhalation of, these products. The medical diagnosis was mild organophosphate poisoning. Protective clothing was not provided despite a precautionary statement on the label of the diazinon product to the effect that protective clothing should be worn. Labels of both products carry the warning that skin contact should be avoided, and give details of procedures to be carried out if this occurs. This incident is currently the subject of litigation.

A lousicide containing deltamethrin caused itchy eyes and a skin rash in four people applying the product to sheep. The route of exposure was unknown but was possibly by skin contact or via the vapour. The property owner had used the product for years with no previous problems and had advised staff on precautions to take when handling the product. The label carries a statement warning of the need for protective clothing, and to avoid contact with eyes and skin.

Inhalation of the vapour of a product containing ivermectin for use as a topical ectoparasiticide/anthelmintic in cattle caused headache, diarrhoea, vomiting and a running nose in a woman on two occasions. A physician diagnosed an allergy to ivermectin.

A farmer developed an allergic reaction to the hydrocarbon solvent in a product containing the active constituent moxidectin for use as a topical ectoparasiticide/ anthelmintic in cattle. The farmer had previously experienced adverse reactions to another product containing a similar solvent, and has been advised by his doctor to avoid further contact with such products. Such reactions are fairly rare relative to the quantity of products used.

A woman employed at a cattle feedlot suffered an accidental needle puncture in the hand with a syringe containing the antibiotic tilmicosin phosphate, used for respiratory disease in cattle. There was immediate numbness in the hand and the arm, with the hand becoming stiff. Vomiting began four hours later at which time the hand was severely swollen. The heart rate and blood pressure fluctuated. The woman was hospitalised for 24 hours and recovered. Bruising and swelling of the hand lasted for two days. Label safety directions advise caution to avoid accidental injection.

Olaquindox, a growth promotant for addition to pig feed, caused contact dermatitis in a piggery worker who had handled substances containing the chemical. He developed a widespread weeping dermatitis, affecting the hands, forearms, arms and neck. This chemical received a public nomination for review by the the NRA's Existing Chemicals Review Program but was not rated sufficiently high to be included in the Priority Candidate Review List.

A product containing pyrethrins and piperonyl butoxide, used for topical flea control on cats, was suggested as the cause of blisters, redness, pustules and swelling on one hand and arm of a woman, two days post application and then on the other hand and arm two weeks later. A medical practitioner diagnosed a contact allergy. This was possibly an idiosyncratic reaction to one of the ingredients of the product.

Appendix A

SUMMARY OF PRODUCT RELATED AND POSSIBLY PRODUCT RELATED ADVERSE EXPERIENCE REPORTS 1995

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. There were 21 reports classified as not product related which are not included. This group also contains 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. Also included is a summary of reported human adverse experiences related to the use of veterinary chemicals.

CATS Contd.

CATTLE