FDA-CVM FOIA Response 2015-4864 November 2015 · FDA-CVM FOIA Response 2015-4864 November 2015 ... The Center's ADE review process is ... Afoxolaner and fluralaner are both approved

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FDA-CVM FOIA Response 2015-4864 November 2015

This serves as the response to your Freedom of Information Act (FOIA) request for records regarding adverse event reports received for afoxolaner and fluralaner. A search of CVM’s Adverse Drug Event (ADE) database was performed on 11/23/2015. The search parameters were: Active ingredient(s): afoxolaner and fluralaner Reports received: From 1/1/2013 through 6/17/2015 Case type: Spontaneous ADE report For each drug, we have provided the ‘CVM ADE Comprehensive Clinical Detail Report Listing’, which is a cumulative listing of adverse experiences in reports submitted to CVM. General Information about CVM’s ADE Database The primary purpose for maintaining the CVM ADE database is to provide an early warning or signaling system to CVM for adverse effects not detected during pre-market testing of FDA-approved animal drugs and for monitoring the performance of drugs not approved for use in animals. Information from these ADE reports is received and coded in an electronic FDA/CVM ADE database. CVM scientists use the ADE database to make decisions about product safety which may include changes to the label or other regulatory action. CVM’s ADE reporting system depends on detection and voluntary reporting of adverse clinical events by veterinarians and animal owners. The Center's ADE review process is complex, and for each report takes into consideration confounding factors such as:

• Dosage • Concomitant drug use • The medical and physical condition of animals at the time of treatment • Environmental and management information • Product defects • Extra-label (off label) uses

The specifics of these complex factors cannot be addressed in the CVM ADE Comprehensive Clinical Detail Report Listing. How to Use the CVM ADE Comprehensive Clinical Detail Report Listing Clinical signs reported for an active ingredient are listed in order from most frequently reported to least frequently reported, grouped by species and route of administration.

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FDA-CVM FOIA Response 2015-4864 November 2015

More than one clinical sign may have been reported per ADE case report, so the ‘Number of times reported’ column is not additive and does not necessarily represent the total number of reports received. Also, if a manufacturer reports multiple products in a single ADE case report, clinical signs are associated with each of the manufacturer’s products. Afoxolaner and fluralaner are both approved for oral use in dogs only. For the time period of the ADE database search (1/1/2013 - 6/17/2015), there were a total of 5,087 ADE reports received for afoxolaner for dogs, and a total of 2,467 ADE reports received for fluralaner for dogs. When reviewing the CVM ADE Comprehensive Clinical Detail Report Listing, the reader should be aware that:

• For any given ADE report, there is no certainty that the reported drug caused the adverse event. The adverse event may have been related to an underlying disease, using other drugs at the same time, or other non-drug related causes. The clinical detail listing does not include information about underlying diseases, other drugs used at the same time, other non-drug related causes, or the final outcome of the reaction.

• The accuracy of information regarding the ADE is dependent on the quality of information received from the reporting veterinarian or animal owner.

• Accumulated ADE reports should not be used to calculate incidence rates or estimates of drug risk, because there is no accurate way to determine how many animals were given the drug, which is needed as the denominator in calculations of incidence and relative risk.

• It is inappropriate to make use of adverse event data to compare the safety of different products. For example, if a drug is widely used to treat certain conditions, there may be more ADEs for that drug than another product that is not used as often. This would not mean that the first drug was more unsafe than the second. The number of reports simply represents the number of ADEs received for a particular drug and should not be used for any type of comparison purposes.

• Underreporting occurs with most adverse event reporting systems. The frequency of reporting for a given drug product varies over time, and may be greater when the drug is newly marketed, or when media publicity occurs.

• Information on how the drugs were used (for indications on the product label or in an extra label manner) is not provided in the clinical detail listing.

More information about CVM’s ADE Reporting System can be found on our web site at: http://www.fda.gov/AnimalVeterinary/SafetyHealth/default.htm.

http://www.fda.gov/AnimalVeterinary/SafetyHealth/default.htm

CVM ADE Comprehensive Clinical Detail Report Listing

Cumulative Date Range : 01-Jan-2013 -thru- 17-Jun-2015

For case type: Spontaneous

DRUG: AFOXOLANER

Route of Administration: Species:

ORAL

Cat

Sign : Number of Times Reported :

ACCIDENTAL EXPOSURE 2

FEVER 1

FOAMING AT THE MOUTH 1

ITCHING 1

NOT EATING 1

SHAKING 1


MISSING

Dog


VOMITING 9

APPETITE LOSS 3

DIARRHOEA 3

ITCHING 3

ATAXIA 2

FLAKING SKIN 2

LETHARGY 2

ABNORMAL RADIOGRAPH FINDING 1

ABNORMAL TEST RESULT 1

BUN LOW, BLD 1

CARDIAC FAILURE 1

CERVICAL VENTROFLEXION 1

COUGH 1

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DERMATITIS 1

DISORIENTATION 1

DRY SKIN 1

ELEVATED TOTAL BILIRUBIN 1

GENERALISED SKIN REACTION 1

HIVES 1

HYPERCALCAEMIC CONDITION 1

HYPEREXTENSION 1

HYPERGLYCAEMIA 1

HYPERTENSION 1

INCREASED SKIN SENSITIVITY 1

INEFFECTIVE, FLEAS 1

LACK OF EFFICACY 1

LATERAL RECUMBENCY 1

MUSCULOSKELETAL DISORDER NOS 1

PICA NOS 1

POLYCYTHEMIA 1

PRURITUS 1

PULMONARY DISORDER NOS 1

PUSTULES 1

RESTLESSNESS 1

SCRATCHING 1

SEIZURE NOS 1

SKIN DISORDERS NOS 1

TREMOR 1

VESTIBULAR DISORDER NOS 1


ORAL

Dog


VOMITING 1,483

LETHARGY 646



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DIARRHOEA 591

PRURITUS 415

ITCHING 349

SEIZURE NOS 343

SCRATCHING 217

PANTING 192

NOT EATING 187

ANOREXIA 170

ERYTHEMA 170

BEHAVIOURAL DISORDER NOS 154

APPETITE LOSS 127


RESTLESSNESS 105

HIVES 100

ALLERGIC REACTION 94

FEVER 81

SHAKING 81

BLOODY DIARRHOEA 76

SKIN DISORDERS NOS 74

FLAKING SKIN 71

ANXIETY 70

ATAXIA 70

DRY SKIN 70

SELF TRAUMA 70

LOOSE STOOL 66

ELEVATED ALT 65

DEATH 60

HYPERACTIVITY 52

ELEVATED SAP 50

PACING 50



INEFFECTIVE, FLEAS 48

ADIPSIA 46

LACK OF EFFICACY 46

DECREASED APPETITE 43

VOCALISATION 43

WEIGHT LOSS 43

AGITATION 42

SKIN LESION NOS 42

ELEVATED TEMPERATURE 41

RASH 41

TREMBLING 41

INAPPETENCE 40

PAPULE 38

REDDENING OF THE SKIN 37

ALOPECIA 36

DEATH BY EUTHANASIA 36

POLYDIPSIA 36

DEPRESSION 35

LEUCOCYTOSIS 34

ANAEMIA NOS 33

HOT SPOT (PYOTRAUMATIC DERMATITIS) 32

LICKING 32


PICA NOS 32

THROMBOCYTOPENIA 32

ELEVATED BUN 30

FACIAL OEDEMA 30

TREMOR 30

TWITCHING 30

INAPPROPRIATE URINATION 29



ABNORMAL RADIOGRAPH FINDING 28

DYSPNOEA 28

PAIN NOS 28

SKIN SORE 28

HYPERSALIVATION 27

PINNAL REDDENING 26

SKIN INFLAMMATION NOS 26

HEAD SHAKE 25

TACHYCARDIA 25

ALOPECIA LOCAL 24

FACIAL SWELLING 24

BLOOD IN FAECES 23

NEUTROPHILIA 23

WALKING DIFFICULTY 23

DROOLING 22

NAUSEA 22

PINNAL OEDEMA 22

POLYURIA 21

AGGRESSION 20

ELEVATED LIVER ENZYMES 20

HAIR LOSS NOS 20

HYPERGLYCAEMIA 20

SKIN DRYNESS 20

ABDOMINAL PAIN 19

HAIR SHEDDING 19

NOT DRINKING 19

SKIN IRRITATION 19

SKIN SCAB 19

DEHYDRATION 18

HIND LIMB ATAXIA 18



REDUCED RESPONSES 18

SLEEPINESS 18

URINARY INCONTINENCE 18

ALOPECIA NOS 17

ELEVATED CREATININE 17

OTITIS EXTERNA 17

PALE MUCOUS MEMBRANE 17

RELUCTANT TO MOVE 17

DISORIENTATION 16

ELEVATED TOTAL BILIRUBIN 16

GAGGING 16

HYPERPHOSPHATAEMIA 16

MONOCYTOSIS 16

OCULAR DISCHARGE 16

SYSTEMIC DISORDER NOS 16

ANAPHYLACTIC-TYPE REACTION 15

COUGH 15

DERMATITIS 15

DIGESTIVE TRACT DISORDER NOS 15

HYPOKALEMIC CONDITION 15

PANCREATITIS 15

PERIORBITAL OEDEMA 15

BLOOD IN VOMIT 14

ELEVATED GAMMA-GLUTAMYL TRANSFERASE (GGT) 14

FLATULENCE 14

INAPPROPRIATE DEFECATION 14

MALODOUR 14

UNABLE TO STAND 14

WEAKNESS 14

ABNORMAL NECROPSY FINDING 13



ABNORMAL ULTRASOUND FINDING 13

COLLAPSE NOS 13

CRYING 13

ELEVATED LIPASE 13

EXCORIATION 13

HYPERPIGMENTATION 13

HYPERTHERMIA 13

LYMPHOPENIA 13

NEUROLOGICAL SIGNS NOS 13

PINNAL ERYTHEMA 13

PR-LIVER, LESION(S) 13

DECREASED ACTIVITY 12

ELEVATED AMYLASE 12

HIND LIMB PARESIS 12

LAMENESS 12

LATERAL RECUMBENCY 12

LIVER DISORDER NOS 12

LOCALISED HAIR LOSS 12

PYODERMA 12

RETCHING 12

SELF MUTILATION 12

ABNORMAL STOOL COLOURATION 11

APATHY 11

HAIR MODIFICATION NOS 11

HYPERAESTHESIA 11

HYPERPROTEINAEMIA 11

HYPOGLYCAEMIA 11

LISTLESS 11

MALAISE 11

NOT SLEEPING 11



PUSTULES 11

STIFFNESS NOS 11

URTICARIA 11

CIRCLING 10

FOAMING AT THE MOUTH 10

HAIR CHANGE 10

ABNORMAL BREATHING 9

ACCIDENTAL EXPOSURE 9

CHLORIDE LOW, BLOOD 9

CONSTIPATION 9

CRUST 9

DECREASED BOWEL MOVEMENTS 9

DECREASED URINE CONCENTRATION 9

DRY MUCOUS MEMBRANE 9

EYE DISORDER NOS 9

FALLING 9

HIDING 9

HYPOALBUMINAEMIA 9

HYPOPROTEINAEMIA 9

LEUCOPENIA 9

LYMPHOCYTOSIS 9

RED EYE 9

SKIN HYPERAEMIA 9

STOMACH UPSET 9

TACHYPNOEA 9

DRUNKEN GAIT 8

EYE REDNESS 8

HAEMATURIA 8

HYPEREXCITATION 8

INCREASED BORBORYGMUS 8



PR-KIDNEY(S), LESION(S) 8

PROTEINURIA 8

PR-SKIN, LESION(S) 8

RECUMBENCY 8

RENAL DISORDER NOS 8

RETICULOCYTOSIS 8

STUMBLING GAIT 8

URINARY TRACT INFECTION 8

WHEEZING 8

ELEVATED AST 7

ELEVATED BILE ACIDS 7

GAIT ABNORMALITY 7

HEAD TILT 7

HEAD TREMOR 7

HYPERGLOBULINEMIA 7

HYPERKALEMIC CONDITION 7

HYPERSENSITIVITY NOS 7

HYPONATREMIA 7

ITCHY SKIN 7

LABOURED BREATHING 7

LOCAL SWELLING (NOT APPLICATION SITE) 7

MUCOUS STOOL 7

MUSCULOSKELETAL PAIN 7

PROPRIOCEPTION ABNORMALITY 7

SHIVERING 7

URINE ABNORMALITIES NOS 7

ABNORMAL RED BLOOD CELL 6

ALLERGIC SKIN REACTION 6

BACTERIAL SKIN INFECTION NOS 6

BALANCE PROBLEM 6



BREATHING DIFFICULTY 6

BRUISING 6

CHEWING 6

CONFUSION 6

EOSINOPHILIA 6

GALL BLADDER & BILE DUCT DISORDER NOS 6

HAEMATEMESIS 6

HYPERCALCAEMIC CONDITION 6

HYPOCALCAEMIC CONDITION 6

HYPOTHERMIA 6

HYPOTHYROIDISM 6

LIP OEDEMA 6

MELAENA 6

MUSCLE TREMOR 6

MYDRIASIS 6

NYSTAGMUS 6

OVERDOSE 6

PINNAE DISORDER 6

RECTAL BLEEDING 6

SLEEP DISTURBANCE NOS 6

SODIUM:POTASSIUM LOW, BLOOD 6

TENESMUS 6

UNCOMFORTABLE 6

UNSTEADY GAIT 6

APPREHENSION 5

CARDIAC DISORDER NOS 5

CARDIAC ENLARGEMENT 5

COLITIS 5

DRINKING A LOT 5

ELEVATED CREATININE-KINASE (CK) 5



ERUPTION 5

GASTRITIS 5

GENERAL HAIR LOSS 5

GENERALISED ITCHING 5

HEAD BOBBING 5

HYPOPHOSPHATAEMIA 5

ICTERUS 5

INVOLUNTARY DEFECATION 5

LOSS OF BOWEL CONTROL 5

MOIST DERMATITIS 5

POLYCYTHEMIA 5

PR-HEART, LESION(S) 5

PULMONARY CONGESTION 5

RENAL FAILURE 5

SKIN SWELLING 5

SNEEZING 5

STAGGERING 5

STAR-GAZING 5

SWELLING AROUND EYE 5

SWELLING NOS 5

SWOLLEN LYMPH NODE 5

TARRY OR BLACK STOOL 5

ADRENAL GLAND DISORDER NOS 4

ALKALINE URINE 4

ALLERGIC DERMATITIS 4

BASOPHILIA 4

BILIRUBINURIA 4

BRADYCARDIA 4

COLLAPSE 4

COLLAPSE OF LEG 4



CONJUNCTIVITIS 4

DROOPING EYELID 4

DRY MOUTH 4

EAR INFECTION NOS 4

ELEVATED CHOLESTEROL (TOTAL) 4

EMESIS 4

ENLARGED LIVER 4

EPISTAXIS 4

EYES ROLLING BACK 4

FLUID IN ABDOMEN NOS 4

GASTROENTERITIS 4

GLAZED EYE 4

HAEMORRHAGIC DIARRHOEA 4

HALLUCINATION 4

HEART MURMUR 4

HEMATOCRIT(HCT) HIGH, BLOOD 4

HEPATITIS 4

HEPATOMEGALY 4

HYPOGLOBULINEMIA 4

IMPAIRED VISION 4

INEFFECTIVE, TICKS 4

JAUNDICE 4

LIP SMACKING 4

LOCALISED ITCHING 4

MYOCLONIC JERK 4

NEUROLOGICAL SYMPTOMS NOS 4

NEUTROPENIA 4

PANCREAS DISORDER 4

PANCREAS ENDOCRINE DISORDER NOS 4

PANCREATIC ENZYMES HIGH, BLOOD 4



PETECHIAE NOS 4

PLATELETS HIGH, BLOOD 4

PLEURAL EFFUSION 4

PNEUMONIA 4

POLYPNOEA 4

PROPRIOCEPTION LOSS 4

PR-SPLEEN, LESION(S) 4

SICKNESS 4

SWOLLEN LIP 4

UNPALATABLE 4

UNRESPONSIVE TO STIMULI 4

ABDOMINAL CAVITY DISORDER NOS 3

ABDOMINAL MASS 3

ABNORMAL PUPIL LIGHT REFLEX 3

ABNORMAL SPERMATOZOA 3

ABNORMAL URINE ODOUR 3

ANAL IRRITATION 3

ANAL SAC DISORDER 3

ANAPHYLAXIS 3

ARCHED BACK 3

BANDS(NEUTROPHILS) HIGH, BLOOD 3

BLINDNESS 3

BLISTERING 3

BLOOD AND LYMPHATIC SYSTEM DISORDER NOS 3

BUN LOW, BLD 3

CARDIAC FAILURE 3

CONVULSION 3

COPPER TOXICITY SIGNS 3

CULTURE/TITER DATA ABNORMAL 3

DISCOLOURED URINE 3



DISTENSION OF ABDOMEN 3

EAR IRRITATION 3

ECCHYMOSIS 3

ECZEMA 3

ELEVATED RENAL PARAMETERS 3

EPIDERMAL COLLARETTE 3

EXERCISE INTOLERANCE 3

FEBRILE 3

GENERAL ILLNESS 3

HAEMORRHAGE NOS 3

HAIR COAT DISCOLOURATION 3

HORIZONTAL NYSTAGMUS 3

HYPERALBUMINAEMIA 3

IMMUNE MEDIATED HAEMOLYTIC ANAEMIA 3

IMMUNE MEDIATED THROMBOCYTOPENIA 3

INCOORDINATION 3

INCREASED SKIN SENSITIVITY 3

INTESTINAL HAEMORRHAGE 3

IRRITABILITY 3

JOINT SWELLING 3

LIMPING 3

LOCALISED RASH 3

LOSS OF CONSCIOUSNESS 3

LOW PLATELET COUNT 3

LUMP 3

MEGAOESOPHAGUS 3

MISCELLANEOUS EATING DISORDER NOS 3

MRI SCAN ABNORMAL 3

MUSCLE SPASM NOS 3

MUSCLE WEAKNESS NOS 3



OPISTHOTONUS 3

PADDLING 3

PAPULAR RASH 3

PARAESTHESIA 3

PARTIAL BLINDNESS 3

PINNAL IRRITATION 3

PODODERMATITIS 3

PR-PANCREAS, LESION(S) 3

PR-SMALL INTESTINE, LESION(S) 3

PULMONARY HAEMORRHAGE 3

PUSTULAR SKIN ERUPTION 3

PYREXIA 3

RED BLOOD CELL DISORDER 3

RENAL TUBULAR DISORDER 3

RESPIRATORY TRACT DISORDER NOS 3

REVERSE SNEEZING 3

SEBORRHOEA 3

SKIN ULCER 3

SMALL LIVER 3

SPLEEN AND RETICULO-ENDOTHELIAL SYSTEM DISORDER NOS 3

SWOLLEN FEET 3

TENSE ABDOMEN 3

THROMBOCYTOSIS 3

TIREDNESS 3

ULCERATIVE DERMATITIS 3

ULTRASOUND, LIVER ABNORMAL 3

UROLITHIASIS 3

VESTIBULAR DISORDER NOS 3

WELT 3

ABNORMAL MENACE REFLEX TEST 2



ACIDIC URINE 2

ACIDOSIS 2

ADDISON'S DISEASE 2

ALLERGY NOS 2

ALOPECIA GENERAL 2

ANGIOEDEMA 2

ARRHYTHMIA 2

BALANCE IMPAIRED 2

BELCHING 2

BLINKING 2

BLOOD IN URINE 2

BOIL 2

BRAIN DISORDER NOS 2

BREATHLESSNESS 2

CARDIOMYOPATHY 2

CHRONIC RENAL FAILURE 2

CONFUSED 2

CONGESTED MUCOUS MEMBRANE 2

CREATININE LOW, BLOOD 2

CRYSTALLURIA 2

CYANOSIS 2

DECREASED PACKED CELL VOLUME (PCV) 2

DECREASED PERCENTAGE OF RETICULOCYTES 2

DEPRESSED REFLEXES 2

DERMAL THICKENING 2

DETERIORATION OF MUSCLE FUNCTION 2

DISSEMINATED INTRAVASCULAR COAGULATION 2

DISTRESS 2

DROWSINESS 2

DRUG DOSE ADMINISTRATION INTERVAL TOO SHORT 2



DRY COAT 2

ELECTROLYTE DISORDER 2

EMESIS (MULTIPLE) 2

ENCEPHALITIS 2

EPILEPTIC SEIZURE 2

EXCESSIVE LICKING AND/OR GROOMING 2

EXCITATION 2

EXTERNAL EAR DISORDER NOS 2

EYEBALL PROTRUSION 2

FACE AND NECK SWELLING 2

FASCICULATION 2

FUNGAL SKIN INFECTION NOS 2

GASTRIC BLOAT 2

GASTRIC DISTENSION 2

GENERALISED RASH 2

GOOSE STEPPING 2

GREASY SKIN 2

HAEMOLYTIC ANAEMIA 2

HALITOSIS 2

HEMOGLOBIN(HB) HIGH, BLOOD 2

HEPATIC NECROSIS 2

HEPATIC VASCULAR DISORDER 2

HYPERKERATOSIS 2

HYPERMETRIA 2

HYPERNATREMIA 2

ILLNESS NOS 2

IMPAIRED CONSCIOUSNESS 2

INCREASED BOWEL MOVEMENTS (FREQUENCY) 2

INCREASED COAGULATION TIME 2

INCREASED HEART RATE 2



INCREASED RESPIRATORY RATE 2

INCREASED SENSITIVITY TO SOUND 2

INCREASED SWEATING 2

INCREASED YAWNING 2

INJECTION SITE LUMP 2

INJECTION SITE SWELLING 2

INTESTINAL STASIS 2

INVOLUNTARY MOVEMENT 2

IRREGULAR BREATHING 2

JOINT PAIN NOS 2

LIMB WEAKNESS 2

LIP LICKING 2

LIVER TUMOUR 2

LOCOMOTOR DISTURBANCE 2

MAGNESIUM HIGH, BLOOD 2

MENTAL CONFUSION 2

MONOCYTOPENIA 2

MOUTH PAIN 2

MUSCLE SHAKING 2

NASAL DISCHARGE 2

NERVOUS SYSTEM NEOPLASM 2

NT - CHRONIC INTERSTITIAL NEPHRITIS 2

NT - HYPERTROPHIC CONCENTRIC CARDIOMYOPATHY 2

NT - LYMPHOPLASMACYTIC ENTERITIS 2

ORAL BLEEDING 2

ORAL CAVITY DISORDER NOS 2

OTHER BLOOD DISORDER NOS 2

OTHER EAR DISORDER NOS 2

OTITIS NOS 2

PARALYSIS NOS 2



PEELING SKIN 2

PERIODONTAL DISORDER 2

PR-ADRENAL(S), LESION(S) 2

PR-INTEST, LESION(S) 2

PR-LUNG(S), LESION(S) 2

PROLONGED CAPILLARY REFILL TIME 2

PULMONARY DISORDER NOS 2

PULMONARY OEDEMA 2

QUADRIPARESIS 2

REGURGITATION 2

RENAL VASCULAR DISORDER 2

RESPIRATORY DISTRESS 2

SCALE 2

SCALY CONDITION NOS 2

SCOOTING 2

SKIN SLOUGH 2

SKIN TUMOUR NOS 2

SPLENIC NEOPLASM 2

SQUINTING 2

STIFFNESS LIMB 2

STROKE 2

SWALLOWING DIFFICULT 2

SWOLLEN EYE 2

SWOLLEN FACE 2

THIRD EYELID PROLAPSE 2

TITER DATA ABNORMAL 2

TONGUE DISORDER NOS 2

TREMOR OF LIMB 2

UNABLE TO RISE 2

UNCONSCIOUS 2



URINE LEAKAGE 2

WEIGHT GAIN 2

WHEAL 2

ABDOMINAL CAVITY HAEMORRHAGE 1

ABDOMINAL EFFUSION 1

ABNORMAL MOVEMENT NOS 1

ABNORMAL OESTRUS NOS 1

ACUTE RENAL FAILURE 1

ALBUMIN HIGH, URINE 1

ALKALOSIS 1

ALT HIGH 1

AORTIC STENOSIS 1

APPETITE DISORDER NOS 1

APPLICATION SITE BLEEDING 1

APPLICATION SITE ERYTHEMA 1

APPLICATION SITE SCAB 1

ARTHROPATHY NOS 1

ASCITES 1

ASTHMA 1

AUTOIMMUNE DISORDER NOS 1

BARKING 1

BILE ACIDS HIGH, BLOOD 1

BILIRUBIN(TOTAL) HIGH, BLOOD 1

BITING 1

BLADDER INCONTINENCE 1

BLEPHARITIS 1

BLOATED 1

BLOOD DYSCRASIA NOS 1

BLOOD IN TRACHEA 1

BLUE EYE 1



BRONCHITIS 1

BRONCHOPNEUMONIA 1

BUMPING INTO WALLS 1

BURN 1

CATARACT 1

CELLULITIS 1

CENTRAL NERVOUS SYSTEM DEPRESSION 1

CENTRAL NERVOUS SYSTEM DISORDER NOS 1

CEREBRAL VASCULAR ACCIDENT 1

CERVICAL VENTROFLEXION 1

CHATTERING OF TEETH 1

CHEWING DISORDER 1

CHLORIDE HIGH, BLOOD 1

CHOLANGIOHEPATITIS 1

CLONIC MUSCLE SPASM 1

CLOSED EYELID 1

CLOUDY EYE 1

COAGULOPATHY 1

COGNITIVE AND ATTENTION DISORDERS NOS 1

COGNITIVE IMPAIRMENT 1

COLIC 1

CONGESTION OF MUCOUS MEMBRANE 1

COPROPHAGIA 1

CORNEAL DISORDER NOS 1

COUGHING BLOOD 1

CUSHINGS DISEASE NOS 1

CUTANEOUS OEDEMA 1

CYANOTIC SPORTS/ BLOTCHY SKIN 1

CYSTITIS 1

DEAFNESS 1



DEAFNESS NOS 1

DECREASED BODY TEMPERATURE 1

DECREASED PULSE OXYGENATION 1

DECREASED RED BLOOD CELL COUNT 1

DENTAL CALCULUS 1

DENTAL DISEASE 1

DERMAL CYST(S) 1

DERMATOSIS NOS 1

DIABETES 1

DILATED PUPILS 1

DISORIENTED STATE 1

DRUG ADMINISTRATION ERROR 1

DRY EYE 1

DRY NOSE 1

DULL 1

DULLNESS 1

DUODENITIS 1

EAR DISCHARGE 1

EAR FLAP OEDEMA 1

EAR PAIN 1

EAR TWITCHING 1

ELEVATED TRIGLYCERIDE 1

ENDOCRINE NEOPLASM 1

ENLARGED KIDNEY(S) 1

ENLARGED LYMPH NODE 1

EOSINOPENIA 1

EPILEPSY 1

EPIPHORA 1

EROSION 1

ERUCTATION 1



EXCESS TEAR FLOW 1

EXCESSIVE THIRST 1

EYE INFLAMED 1

EYE INFLAMMATION NOS 1

EYE PARALYSIS 1

EYELID OEDEMA 1

FACIAL NERVE DISORDER 1

FACIAL PARALYSIS 1

FAECAL INCONTINENCE 1

FAINTING 1

FATIGUE 1

FIXED PUPIL 1

FOAM IN THE NOSE 1

FOLLICULITIS 1

FOUND DEAD 1

FRACTURE 1

FREQUENT URINATION 1

FURUNCULOSIS 1

GASTRIC VOLVULUS 1

GENERAL PAIN 1

GENERALISED SKIN REACTION 1

GINGIVITIS 1

GLUCOSURIA 1

GUM DISORDER NOS 1

GUT SOUNDS DECREASED 1

GUT SOUNDS INCREASED 1

HAEMOCONCENTRATION 1

HAEMORRHAGIC GASTROENTERITIS 1

HAEMOTHORAX 1

HAIR STANDING ON END 1



HEAVY SWEATING 1

HEPATIC DISORDER NOS 1

HEPATIC FIBROSIS 1

HEPATIC NEOPLASM 1

HEPATIC TUMOUR 1

HEPATOPATHY 1

HICCUP 1

HIND LIMB PARALYSIS 1

HISTIOCYTOMA 1

HYPEREXTENSION 1

HYPERTENSION 1

HYPERTRICHOSIS 1

HYPERVENTILATION 1

IMPAIRED PROPRIOCEPTION 1

IMPAIRED VOCALISATION 1

INCORRECT DOSE ADMINISTERED 1

INCREASED APPETITE 1

INCREASED SALIVATION 1

INCREASED SENSITIVITY TO LIGHT 1

INCREASED URINE CONCENTRATION 1

INDIGESTION 1

INEFFECTIVE, ASCARIDS 1

INEFFECTIVE, OTHER DRUG(S) 1

INJECTION SITE ABSCESS 1

INJECTION SITE INFLAMMATION 1

INTENTION TREMOR 1

INTERSTITIAL NEPHRITIS 1

INTESTINAL CONGESTION 1

IRON DEFICIENCY ANAEMIA 1

ISOSTHENURIA 1



JOINT INFLAMMATION 1

JOINT OEDEMA 1

JOINT STIFFNESS 1

LACK OF AWARENESS 1

LACK OF COORDINATION 1

LACRIMATION INCREASED 1

LARYNGEAL PARALYSIS 1

LICK GRANULOMA 1

LIP DISORDER NOS 1

LIP ERYTHEMA 1

LOCALISED PAIN NOS 1

LOCALISED SKIN REACTION 1

LOSS OF CONCENTRATION 1

LOSS OF HEARING 1

LOSS OF VISION 1

LOSS OF VOLUNTARY MOVEMENT 1

LYMPHADENOPATHY 1

LYMPHOMA 1

LYMPHOSARCOMA 1

MENTAL IMPAIRMENT NOS 1

METASTATIC NEOPLASIA 1

MOTOR DYSFUNCTION NOS 1

MULTIPLE ORGAN HAEMORRHAGE 1

MUSCLE CONTRACTURE 1

MUSCLE STIFFNESS 1

MUSCLE WASTING 1

MYOCLONUS 1

MYOGLOBINURIA 1

NAIL DISORDERS NOS 1

NEOPLASIA NOS 1



NEUROMUSCULAR DISORDER NOS 1

NT - ADENOCARCINOMA 1

NT - HEPATIC LIPIDOSIS (STEATOSIS) 1

NT - HEPATIC OR BILIARY TUMOUR

(HEPATOCARCINOMA/CHOLANGIOCARCINOMA/

ADENOMA/CHOLANGIOMA)

1

NT - NECROTIC HEPATITIS 1

OEDEMA OF THE EXTREMITIES 1

OESOPHAGITIS 1

OFF COLOUR 1

ORAL PAIN 1

ORGAN PETECHIAE 1

OTHER COAGULATION ABNORMALITY 1

PACKED CELL VOL(PCV) HIGH, BLD 1

PAINFUL URINATION 1

PANCYTOPENIA 1

PANNICULITIS 1

PAPILLOMA 1

PARALYSIS 1

PARTIAL LACK OF EFFICACY 1

PENILE ERECTION 1

PERICARDIAL EFFUSION 1

PERICARDIAL HAEMORRHAGE 1

PERINATAL MORTALITY 1

PERITONITIS 1

PIGMENTATION DISORDER 1

PIMPLES 1

POLYRADICULONEURITIS 1

POOR COAT CONDITION 1

POOR PERIPHERAL CIRCULATION 1

PORTACAVAL SHUNT 1

PR-ASCITES 1



PR-BLADDER, LESION(S) 1

PR-BRAIN, LESION(S) 1

PR-COLON, LESION(S) 1

PR-LYMPH NODE(S), LESION(S) 1

PR-MENINGES, LESION(S) 1

PR-MULTIPLE SITES, CONGESTION 1

PROLAPSE OF THE NICTITATING MEMBRANE 1

PROSTATE HYPERTROPHY 1

PROTRUSION MEMBRANA NICTITANS 1

PR-STOMACH, LESION(S) 1

PR-TRACHEA, LESION(S) 1

PURULENT LESION(S) 1

PYELONEPHRITIS 1

RED BLOOD CELLS(RBC) ABNORMAL 1

REGENERATIVE ANAEMIA 1

RESPIRATORY ARREST 1

RESPIRATORY SIGNS 1

RESPIRATORY SOUND 1

RESPIRATORY TRACT INFECTION NOS 1

RETICULOCYTES LOW, BLOOD 1

RETINAL DISORDER NOS 1

RIGIDITY 1

RUBBING 1

SEDATION 1

SENSATION LOSS 1

SEPTICAEMIA 1

SHOCK 1

SIGHT AFFECTED 1

SKIN AND TISSUE INFECTION NOS 1

SKIN NECROSIS 1



SKIN OEDEMA 1

SKIN VASCULAR DISORDER NOS 1

SMELL DISORDER NOS 1

SOMNOLENCE 1

SORE LIP 1

SPLENOMEGALY 1

SPONDYLOSIS 1

STERILE 1

STIFF GAIT 1

STRANGURIA 1

STRIDOR (UPPER RESPIRATORY; FOR LOWER RESPIRATORY SEE

ALSO BRONCHIAL RALE) 1

SUDDEN DEATH 1

SUNKEN EYES 1

SWOLLEN GUM 1

SWOLLEN TONGUE 1

SYNCOPE 1

TEETH GRINDING 1

TEMPORARY BLINDNESS 1

TESTICULAR ERYTHEMA 1

TETANY 1

THORACIC CAVITY DISORDER NOS 1

THROAT PAIN 1

THROMBOSIS 1

TONGUE PROTRUSION 1

TONIC-CLONIC SEIZURE 1

TRIGLYCERIDES HIGH, BLOOD 1

UNCLASSIFIABLE ADVERSE EVENT 1

UNEXPLAINED DEATH 1

UNILATERAL PARESIS 1

URINARY BLADDER DISORDER NOS 1



URINARY RETENTION 1

URINARY TENESMUS 1

URINARY TRACT BLEEDING 1

URINARY TRACT DISORDER NOS 1

URINE ABNORMAL, SEDIMENT 1

URTICARIAL ERYTHEMA 1

URTICARIAL RASH 1

VAGINAL DISCHARGE 1

VAGINITIS 1

VASCULITIS 1

VENTRICULAR ARRHYTHMIA 1

VON WILLEBRANDS DISEASE 1

WEAK PULSE 1

WEAKNESS OF LIMB 1


OTHER

Dog


APPETITE LOSS 2

DIARRHOEA 2


TOPICAL

Dog


GINGIVAL DISORDER 1

PRURITUS 1

SKIN HYPERAEMIA 1


UNKNOWN

Dog


VOMITING 18

PRURITUS 13

LETHARGY 8

SEIZURE NOS 7



DIARRHOEA 6

ITCHING 6

ERYTHEMA 3

PANTING 3

SCRATCHING 3

AGITATION 2

ALOPECIA NOS 2

ANOREXIA 2

APPETITE LOSS 2

REDDENING OF THE SKIN 2

RESTLESSNESS 2


ALOPECIA 1

BALANCE PROBLEM 1

BEHAVIOURAL DISORDER NOS 1

BLOOD IN FAECES 1

BLOODY DIARRHOEA 1

COLIC 1

DEATH 1

DECREASED APPETITE 1

DEPRESSION 1

DISORIENTATION 1

ERYTHEMATOUS RASH 1

FLATULENCE 1

GENERALISED ITCHING 1

GENERALISED RASH 1

GINGIVAL DISORDER 1

HIVES 1

HOT SPOT (PYOTRAUMATIC DERMATITIS) 1

HYPERTHERMIA 1



IMMUNE MEDIATED HAEMOLYTIC ANAEMIA 1

INAPPROPRIATE DEFECATION 1

INCREASED BORBORYGMUS 1

LIP LICKING 1

LIVER FAILURE 1

LOCALISED PAIN NOS 1

LOOSE STOOL 1

MALODOUR 1


NAUSEA 1

NOT EATING 1

PACING 1

PAPULE 1

SKIN HYPERAEMIA 1

TEAR FLOW INCREASED 1

TIREDNESS 1

TITER DATA ABNORMAL 1

TREMOR 1

WALKING DIFFICULTY 1

WEIGHT LOSS 1


ORAL

Human


VOMITING 1


TOPICAL

Human


ALLERGIC REACTION 1

BURNING MOUTH SENSATION 1

EYE IRRITATION 1

HIVES 1



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MENTAL CONFUSION 1

RASH 1

THROAT IRRITATION 1

TINGLING SENSATION 1

TONGUE PARAESTHESIA 1

WELT 1


UNKNOWN

Human


HIVES 3

PRURITUS 3

RASH 3

ALLERGIC REACTION 1

COUGH 1

DERMATITIS 1

DIARRHOEA 1

DIFFICULTY SLEEPING 1

ERYTHEMA 1

LACRIMATION 1

SKIN DRYNESS 1

SKIN LESION NOS 1

SNEEZING 1

SWELLING NOS 1

SWOLLEN LIP 1

VOICE ALTERATION 1

WELT 1



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Documents

FDA-CVM FOIA Response 2015-4864 November 2015 · FDA-CVM FOIA Response 2015-4864 November 2015 ... The Center's ADE review process is ... Afoxolaner and fluralaner are both approved