Adverse Experiences Report 1999 Section 4 Tables

CATS

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Boric acid, menthol and chlorothymol	Topical (ear)	1	1	Nil	Less than fifteen minutes after instilling this product in a cat's left ear, the left third eyelid started to prolapse. No reaction occurred in the right ear. This is the fourth time this veterinarian has observed this type of adverse experience.	Possibly product-related. The clinical signs observed in this cat only occur when foreign material damages the middle ear. For this to occur the tympanic membrane must have been damaged.
Niclosamide monohydrate and pyrantel embonate	Oral	1	1	Nil	The cat was observed to be panting approximately one hour after the treatment was given. The cat started calling and hypersalivating after two hours. It was taken to a vet for treatment. The cat was treated with intravenous fluids and was discharged the following day.	Possibly product-related. The attending veterinarian and the investigating veterinarian both believe that the experience was possibly product-related.
Praziquantel, febantel and pyrantel embonate	Oral	1	1	Nil	About three and a half hours after treatment, the cat's third eyelids protruded, and the cat became unsteady on all four legs.	Product-related. The Registrant of this product indicated that there has been a low level of similar types of experiences to this product reported previously. A new formulation has markedly reduced reports of such adverse reactions.

CATTLE

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Bm86 antigen	Subcutaneous	120	35	Nil	The following reactions occurred in the affected animals on two occasions. Approximately nine to eleven hours after treatment, 35 cattle developed large swellings at the injection sites with varying degrees of lameness (in the forelegs) and depression. Rectal temperatures were slightly elevated (39.1 to 39.7 degrees C). Some of the cattle had muscle tremors and were moderately ataxic. Blood analysis indicated that the cattle were suffering from allergic reactions.	Possibly product-related. The swellings that developed at the injection sites and the associated lameness were most likely related to use of the product. The NRA cannot conclude that the other clinical signs of depression, muscle tremors and ataxia are associated with this product, however it still remains possible.
Cloxacillin	Intramammary	40	5	Nil	Forty cattle were treated with this product at drying-off according to label directions. Five of the cattle showed persistent blue dye excretion for up to fourteen days post-partum. The cows were aged between three and seven years, with minimal mastitis problems.	Product-related. The reason for the extended excretion of blue dye is unknown. Possible causes include cow variation, level of dye in product. As a result of this and similar reports, the level of dye in the product has been reduced.
Cloxacillin	Intramammary	21	10	Nil	Twenty-one cattle were treated with this product at drying-off to prevent mastitis in the subsequent lactation. When the cattle calved (at least 60 days later) ten of them had persistent blue dye in the milk 96 hours post-partum.	Product-related. The reason for the extended excretion of blue dye is unknown. Possible causes include cow variation, level of dye in product. As a result of this and similar reports, the level of dye in the product has been reduced.

CATTLE contd.

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Cloxacillin	Intramammary	65	40	Nil	Sixty-five cattle were treated at drying-off with this product as part of a mastitis prevention program. At calving, Approximately 40 of these cows had persistent blue dye excretion beyond the recommended withholding period.	Product-related. The reason for the extended excretion of blue dye is unknown. Possible causes include cow variation, level of dye in product. As a result of this and similar reports, the level of dye in the product has been reduced.
Cypermethrin and chlorfenvinphos	External	200	20	8	Cattle were treated twelve days prior with no adverse effects. On this occasion, eight calves became ataxic and began frothing at the mouth within four hours of treatment. Three calves died within eight hours, five more died over the next three days.	Product-related. The clinical signs observed in the calves that died (ataxia, frothing at the mouth) are consistent with signs of organophosphate toxicity.
Dinoprost trometamol	Subcutaneous	500	60	6	Five hundred cattle were treated with this product to synchronise oestrus. Approximately two weeks after the injections were given, 60 cattle developed lumps at the injection sites. The attending veterinarian diagnosed the lumps as abscesses. All cattle were treated with antibiotics, although six cattle died.	Possibly product-related. It is well recognised that all injections must be given under hygienic conditions with appropriately sterilised equipment. This type of problem can occur with any injection, as bacteria can be transported under the skin along with the insertion of the needle.

CATTLE contd.

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Monensin	Oral	40	1	1	Forty-four days after a steer was treated with this product to, it was found in the paddock dazed and lethargic, it died overnight. A post mortem indicated that the product had separated in the rumen.	Product-related. An extensive review was made into the manufacturing procedure of this product. It was found that a minor change had occurred during the manufacturing process that may have resulted in a weakness to the mechanism for attaching the wing cap to the body of the capsule. The mould used during this manufacturing process has now been changed to ensure the capsule can not separate. Incidents similar to this have been published previously (5).
Oestradiol	Subcutaneous	200	3	Nil	Three steers developed preputial prolapse after being treated with this product. The farmer contacted a veterinarian who treated the cattle with an anitmicrobial. The farmer was contacted again and the swelling had gone down. Since this report was received, the animals have fully recovered.	Product-related. A label change has been recommended to inform users that these reactions have occurred.
Oestradiol	Subcutaneous	120	20	Nil	Twenty steers were found with prolapsed pizzles 15 days after treatment with this product. All steers were treated with antibiotics and cortisone (injected into the penis). The implants were removed from the worst affected cattle. Seven steers required surgery. All cattle recovered fully.	Product-related. A label change has been recommended to inform users that these reactions have occurred.

CATTLE contd.

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Experience

Classification and comments

Oxytetracycline

and

Ketoprofen

Intramuscular

Nil

A dairy cow was treated with injections of oxytetracycline daily for 4 days to treat a suspected septic arthritis. It was also given injections of the anti-inflammatory agent ketoprofen daily for two days.

The cow's milk was withheld from the vat according to the label directions. The screening test used by the milk factory recorded a positive residue violation by this farm. Independent analysis of the milk indicated that oxytetracycline was present in the milk of this cow, but it was not confirmed whether the level was above the MRL.

Product-related.

Despite adhering to the recommended withholding period for this product, the initial screening test of the milk factory recorded a positive residue violation for this farm.

During the course of the investigation it was discovered that the screening test used by the milk factories can return false positives.

Procaine penicillin

Intramuscular

Nil

Immediately after being injected with this product, a bull collapsed, its heart rate increased, the respiratory rate decreased and its gums became very pale. The animal took three to four hours before it could stand again and complete recovery took 24-48 hours.

Product-related.

Type I Hypersensitivity reaction.

DOGS

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Canine distemper, adenovirus type 2, parvovirus and parainfluenza virus type 2 vaccine (living)	Subcutaneous	1	1	Nil	The dog started sneezing and developed facial swelling shortly after being vaccinated.	Product-related. Type 1 Hypersensitivity.
Carbaryl	External	1	1	Nil	A dog developed ataxia and salivation 12 hours after treatment with this product. It was treated at a veterinary clinic (stomach lavage and external wash) and recovered uneventfully.	Product-related. The clinical signs observed in this dog were consistent with carbaryl toxicity. This type of experience appears to be an idiosyncratic reaction and is very rare.
Copper indomethacin And Bacitracin, neomycin sulfate, polymixin B sulfate	Topical (eye) Topical (eye)	1	1	Nil	A superficial ulcer of the cornea was treated with these products. The ulcer developed into a deep melting ulcer, within one week.	Possibly product-related. It was decided that it was unlikely that either product was involved although it could not be completely ruled out.
Diethylcarbamazine and cyromazine	Oral	1	1	Nil	An owner reported that she has been treating her dog with this product for the last three years. Approximately two years after starting the treatment, the dog developed an irritation of the paws. The dog has been recently diagnosed as having possible liver, kidney and immune dysfunction, resulting in toxins being pushed through the skin.	Possibly product-related. A veterinary pathologist diagnosed the paw irritation as pododermatitis with severe folliculitis and furunculosis, which suggests a bacterial infection. There are other possible causes of this type of disease process, including allergic inhalant dermatitis (atopy), food allergy, bacterial dermatitis (infection), mite infestation and Type 1 hypersensitivities. No follow up diagnostic blood work, radiology or biopsy tests were performed to identify the cause of the liver, kidney or immune system problems. The NRA has not been presented with enough evidence that supports a diagnosis of liver, kidney or immune dysfunction in the dog.

DOGS contd.

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Experience

Classification and comments

Fipronil

External

This dog had been treated with this product every two months for four years without incident. The dog was treated with anti-inflammatories for back pain one week prior to this administration. One hour after being treated with this product, the dog developed wheals 1cm in diameter over the skin. The dog was treated with cortisone for a suspected allergic reaction. The next day, the dog was presented with thickened skin over the neck region, it was again treated with cortisone. The next day, the dog was presented with depression, anorexia, painful abdomen and wheals over the surface of the whole body. A biochemical screen and electrolyte analysis were normal. The dog vomited twice this day and was treated with antibiotics and antiemetic medication. The dog was referred to a specialist. The dog was examined by the specialist and found to be obtunded with thickened skin over the neck (non-painful) and purple skin over the ventral abdomen, which was diagnosed as vasculitis. Urea levels were elevated and there were severe electrolyte imbalances. The dog was treated with cortisone and intra-venous fluids. The urea and electrolyte imbalances improved. The dog died five days later.

Possibly product-related.

The initial development of wheals on the dog's skin appears to be related time-wise to the administration of this product. However, this does not necessarily mean that this product caused this reaction. Previous exposure to the product did not result in such reactions and it is difficult to know if prior administration of non-steroidal anti-inflammatory products played any role in sensitising the skin on this occasion. The NRA concludes that it is possible that the administration of this product led to the development of wheals, but cannot conclude that there was a definite cause and effect relationship.

It is impossible to determine whether the development of further clinical signs observed (eg depression, anorexia, painful abdomen and biochemical and electrolyte disturbances) was related to the use of this product, but it would appear that this was highly unlikely. The lack of other reports of similar experiences supports this.

DOGS contd.

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Imidacloprid	Topical	1	1	Nil	An exudative sore (swollen red, painful and causing hair to stick together) developed within a few hours of application. Thoroughly cleaned and washed and followed by corticosteroid administration (symptomatic treatment). The lesion healed in 10-14 days.	Possibly product-related.
Levamisole and niclosamide	Oral	1	1	1	This dog was taken to a veterinary clinic to be clipped and washed. It was given a worming tablet on leaving. The dog started coughing and gagging within minutes of the treatment, bringing up small amounts of yellow/green material. The dog died within forty minutes. Two post mortems were performed, which revealed that there was some minor damage to the pharyngeal area, some swelling of the brain and cardiomegaly was present.	Possibly product-related. The time-wise relationship between treatment and observed clinical effects may indicate that they are related. The post mortem also indicated that the treatment resulted in some minor damage to the pharyngeal area. There are a number of other factors important in this incident. For example, the post mortem also revealed that the dog had an underlying heart problem, and death through cardiac arrhythmia cannot be excluded.
Living attenuated distemper, canine adenovirus type 2, parvovirus type 2 Living canine parainfluenza virus Inactivated Bordetella bronchiseptica, aluminium salt, thiomersal	Subcutaneous	1	1	Nil	A firm swelling was noticed by the owner at the site of injection of this product soon after treatment.	Product-related. The timing post-vaccination and the fact that this was not a painful reaction would suggest that this was a reaction to the adjuvant in the vaccine.

DOGS contd.

Active constituent	Route of administration	No. Treated	No. Affected	No. Died	Reported Adverse Experience	Classification and comments
Meloxicam	Injectable and Oral	1	1	1	The dog was initially given an injection of this product and a vaccination. It was then treated daily for three days with the oral formulation of this product. The owner phoned to say dog lacked coordination and failed to eat two days after being given the last tablet. Dog was examined the following day and found to have a neurological deficiency in the hind legs. The owner declined further clinical pathology tests. Reported the next day that dog died mid morning - and had vomited blood during the preceding night.	Possibly product-related It appears unlikely that the death of this dog was a result of using this product, although it is impossible to rule out the possibility entirely. As no post mortem was performed it is unknown if the dog was suffering from an underlying, undiagnosed disease which may have contributed to the problems encountered.
Praziquantel, pyrantel embonate and oxantel embonate	Oral	1	1	Nil	Approximately 45 minutes after treatment the dog seemed to become paralysed and was taken to a veterinarian. On presentation, the dog had recovered and no treatment was given.	Possibly product-related. The attending veterinarian suggested that the observed clinical signs may have been associated with the use of the product.
Proligestone	Subcutaneous	3	3	Nil	Three dogs were given an injection of this product to delay their oestrus cycles. Approximately five months after the injections were given the owner noticed that there was some hair loss and depigmentation at the injection sites of all three dogs. In two of the dogs there was some muscle wasting and tissue deficit below the injection sites.	Product-related. Although this reaction was apparently associated with the use of this product the injection site used was inappropriate as there is advice on product label that similar types of problems might be avoided by using recommended injection sites.

DOGS contd.

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Experience

Classification and comments

Yohimbine and

4-aminopyridine

Intravenous

A dog was sedated with another product by intravenous administration. Approximately eight minutes later the dog was given this product intravenously to reverse the effects of the sedative. Within five minutes, the dog experienced excitation and seizures. Diazepam was given to control the seizures and was initially effective, although within 30 minutes the seizures began again, and had a grand mal seizure and became semi-conscious. Cyanosis, elevated heart rate and a high fever developed. The dog suffered a cardiac arrest and died six hours later.

Possibly product-related.

HORSES

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Experience

Classification and comments

Procaine penicillin

Intramuscular

Nil

Immediately after the injection was administered, the horse went into extreme excitation and galloped uncontrollably around the paddock. No injuries occurred.

Product-related.

These types of excitation reactions have been observed in a small percentage of horses treated with products containing procaine penicillin.

Procaine penicillin

Intramuscular

The horse was anaesthetised and undergoing treatment for an infected wound. Within minutes of this product being administered, cardiac irregularities and respiratory arrest occurred. The anaesthetic was ceased. Various treatments were given to attempt resuscitation, but to no avail. The horse died.

Possibly product-related.

PIGS

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Experience

Classification and comments

Mycoplasma hyopneumonide bacterin

Subcutaneous

A group of fifty pigs were vaccinated with this product and three days later, two of the pigs were found dead.

Product related.

Both pigs were presented for post mortems. The pathology report stated that one of the pigs had lung lesions typical with that of a delayed hypersensitivity reaction type 2. The second pig showed no remarkable signs on post mortem.

SHEEP

Active constituent

Route of administration

No.

Treated

No.

Affected

No.

Died

Reported Adverse Reaction

Classification and comments

Levamisole hydrochloride and albendazole oxide

Oral

One ram died approximately 30 minutes after administration of this product. Three further rams died that morning and six more were sick, some became recumbent. A post mortem was carried out on one ram and it revealed no abnormalities. Another ram died overnight.

Possibly product-related.

There was a temporal relationship between the treatment of the animals with this product and the subsequent clinical signs observed.

Levamisole toxicity was postulated as the cause of the death of the rams, although this was not confirmed at post mortem.

The owner originally indicated that water was not available to the rams during the night prior to drenching. This is not recommended when using levamisole as the drench.

HUMAN

Active constituent	Route of administration	No. Treated	No. Reacted	No. Died	Reported Adverse Reaction	Classification and Comments
Fipronil	External	NA	1	Nil	A few hours after applying this product to her dog, the owner was playing with the dog and its fur brushed against her legs. The next morning she had hives over her legs which progressed to her stomach. A Doctor diagnosed an allergic reaction. She was treated with antihistamine tablets. There was a mild improvement on treatment.	Due to the temporal and physical relationship between the application of this product and the development of clinical signs there is the possibility that this adverse experience was product-related.
Fipronil	External	NA	1	Nil	Three hours after applying the product to her dog, the owner brushed her face against the dog's neck where the treatment had been applied. She reported that this cheek and her chin were feeling numb. She washed her face a number of times with soap and water. The next day her skin was normal.	Due to the temporal and physical relationship between the application of this product and the development of clinical signs there is the possibility that this adverse experience was product-related.
Fipronil	External	NA	1	Nil	The owner had been using this product on his cats for the previous twelve months without any reactions. Two days after he applied the product to the cats this time he had a red rash on his forearm. He visited the doctor two days later who prescribed cortisone cream and tablets. The rash resolved with treatment.	There exists the possibility that use of this product resulted in this adverse experience, however this was not confirmed.

HUMAN contd.

Active constituent

Route of administration

No.

Treated

No.

Reacted

No.

Died

Reported Adverse Reaction

Classification and Comments

Fipronil

External

Nil

The owner applied the product to her dog. She wore gloves and washed the gloves and her hands thoroughly after use. Within ½ hour of application she felt a mild tingling sensation on her right wrist and a papular rash approximately 1cm in diameter appeared on the wrist. She applied cortisone cream at home and there was a mild improvement. She had given four doses in total of this product to her cat and dog previously with no skin lesions. She reported that she felt slightly 'shaky' after each application. The owner has a known allergy to soaps and detergents and is under specialist supervision for this. A doctor told her to continue with cortisone cream and the lesion would resolve.

Due to the temporal and physical relationship between the application of this product and the development of clinical signs there is the possibility that this adverse experience was product-related.

HUMAN contd.

Active constituent

Route of administration

No.

Treated

No.

Reacted

No.

Died

Reported Adverse Reaction

Classification and Comments

Fipronil

External

Nil

The day following application of this product to the dog the owner developed swollen lips, which persisted for 36 hours. The reaction has occurred in this person four times now within minutes of touching her dog. Each time the reaction increased in severity to involve the nose, left cheek and area below the left eye.

Due to the temporal and physical relationship between the application of this product and the development of clinical signs there is the possibility that this adverse experience was product-related.

HUMAN contd.

Active constituent

Route of administration

No.

Treated

No.

Reacted

No.

Died

Reported Adverse Reaction

Classification and Comments

Fipronil

External

Nil

Owner has been using product on her dog and cat for the past 12 months. In the last 30 days her son has had several episodes of welts, erythema and pruritus on his legs, arms and stomach. This first occurred after he had been brush cutting and it was assumed to be a plant allergy. It has now re-occurred on several occasions after no contact with plants. One episode occurred after he had brief contact with the cat; he developed welts on his wrist, which then spread to other areas of the body. He has no known chemical allergies and has had no problems in the past, even after close contact with the dog and cat that both sleep in his bed. The doctor diagnosed an allergy and prescribed antihistamines. The product was reapplied to the dog and the boy had close contact with the dog after application and was fine for two days after which he developed a swollen lip and welts on one arm after lying on a floor rug that is also used by the dog and cat.

Due to the temporal and physical relationship between the application of this product and the development of clinical signs there is the possibility that this adverse experience was product-related.

HUMAN contd.

Active constituent

Route of administration

No.

Treated

No.

Reacted

No.

Died

Reported Adverse Reaction

Classification and Comments

Imidacloprid

External

Nil

The owner handled the cat shortly after application of this product to the cat. The skin of the owner's forearm came up in a pruritic rash immediately. The rash gradually subsided.

This incident was classified as possibly product-related. It is important to note that there are numerous possible causes of the condition experienced by this owner, which include plant allergens and other sensitisers or irritants.

Moxidectin

External

Nil

Two people have reported suspected adverse experiences after using product. The symptoms included headache, nausea, tingling feet and numb and tingling lips.

Analysis of the product revealed it conformed to specifications.

Possibly product-related

Other possible causes of these symptoms include reactions to plant allergens, sensitivity to other chemicals in the dairy and viral infections.