Drug Analysis Print Drug name: CLOZAPINE

Transcription

1 Jump to first report page Report type: Spontaneous Total number of reactions*: 9866 Total number of ADR reports: 3259 Total number of fatal ADR reports: 515 Products included in this print - products (PBGs): CLOZARIL DENZAPINE LEPONEX ZAPONEX *It is important to note that one report may contain one or more reactions. Page 1 of 61

2 Report type: Spontaneous System Organ Class Blood disorders Cardiac disorders Congenital disorders Ear disorders Endocrine disorders Eye disorders Gastrointestinal disorders General disorders Hepatic disorders Immune system disorders Infections Injuries Investigations Metabolic disorders Muscle & tissue disorders Neoplasms Nervous system disorders Pregnancy conditions Psychiatric disorders Renal & urinary disorders Reproductive & breast disorders Respiratory disorders Skin disorders Social circumstances Surgical & medical procedures Vascular disorders TOTAL NUMBER OF REACTIONS TOTAL NUMBER OF FATAL ADR REPORTS* * TOTAL NUMBER OF ADR REPORTS* * *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 2 of 61

3 Report type: Spontaneous Glossary/Abbreviations ADR - Adverse Drug Reaction Age group - lists which age groups are included in the either ALL, Adolescent, Adult, Child, Elderly, Infant or Neonate Data lock date - shows data on the database at this specified date and time - High Level Term - see definition of MedDRA MedDRA - this stands for Medical Dictionary for Regulatory Activities, which is the internationally agreed list of terms used for Medicines Regulation. MedDRA groups related adverse drug reaction terms in a hierarchical structure whereby the 'preferred term' () (e.g. tunnel vision) is grouped under the broader heading the 'high level term' () (e.g. visual field disorders). 'High level terms' are contained within the 'system organ class' () (e.g. eye disorders). The 'preferred term' is the most specific term on the, while the 'system organ class' is the most general Multi active products - contain the drug of interest plus one or more other drug s (e.g. co-codamol contains paracetamol and codeine) NEC - appears in MedDRA and stands for Not Elsewhere Classified NOS - appears in MedDRA and stands for Not Otherwise Specified PBG - Product Brand Generic this means drug brand name e.g. Amoxil is a PBG for the drug substance amoxicillin Products included in this print - this is a list of the products for which at least one suspected Adverse Drug Reaction (ADR) report has been received that specifies that product as a 'suspected drug' (i.e. suspected causal association with the reaction). It does not provide an exhaustive list of the products which contain the named drug substance - Preferred Term - see definition of MedDRA Reaction - defines which ADRs are included in the either ALL, Serious or Non-Serious Reporter type - lists the reporter types which are included in the either Patient, Health Professional or ALL (i.e. both) Report run date - the date the was produced Route of admin - lists the route of administration of the suspect drug for which reports are included in the Drug Analysis Print, e.g. ORAL only includes reports where the suspect drug was specified as having been taken by the oral route, or ALL which includes all routes of administration Spontaneous - suspected ADR reports sent in to the Yellow Card Scheme are called spontaneous reports products - contain only the drug substance of interest System Organ Class () - this is the highest level in MedDRA which groups together reactions that affect similar systems/organs in the body Page 3 of 61

4 Report type: Spontaneous Reaction Name Blood disorders Anaemia deficiencies Anaemia of pregnancy Iron deficiency anaemia Anaemias NEC Anaemia Microcytic anaemia Anaemias due to chronic disorders Anaemia of chronic disease Anaemias haemolytic NEC Haemolytic anaemia Coagulopathies Abnormal clotting factor Coagulopathy Eosinophilic disorders Eosinophilia Haematological disorders Blood disorder Hypoglobulinaemia Leukocytoses NEC Leukocytosis Lymphocytosis Monocytosis Neutrophilia Leukopenias NEC Leukopenia Lymphopenia Lymphatic system disorders NEC Hilar lymphadenopathy Lymphadenopathy Marrow depression and hypoplastic anaemias Hypoplastic anaemia Neutropenias Agranulocytosis Neutropenia Platelet disorders NEC Platelet disorder Polycythaemia (excl rubra vera) Polycythaemia Red blood cell abnormal findings NEC Hypochromasia Macrocytosis *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 4 of 61

5 Report type: Spontaneous Reaction Name Blood disorders cont'd Microcytosis Spleen disorders Spleen congestion Splenomegaly Thrombocytopenias Thrombocytopenia Thrombocytoses Thrombocytosis Blood disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 5 of 61

6 Report type: Spontaneous Reaction Name Cardiac disorders Aortic valvular disorders Aortic valve incompetence Cardiac conduction disorders Atrioventricular block Bundle branch block Bundle branch block left Bundle branch block right Conduction disorder Wolff-Parkinson-White syndrome Cardiac disorders NEC Cardiac disorder Cardiovascular disorder Intracardiac thrombus Cardiac hypertensive complications Hypertensive heart disease Cardiac infections and inflammations NEC Myopericarditis Cardiac signs and symptoms NEC Cyanosis Palpitations Cardiac valve disorders NEC Heart valve incompetence Cardiomyopathies Cardiomyopathy Congestive cardiomyopathy Coronary artery disorders NEC Arteriosclerosis coronary artery Coronary artery disease Coronary artery occlusion Coronary artery stenosis Coronary artery thrombosis Endocardial disorders NEC Endocardial fibrosis Heart failures NEC Cardiac failure Cardiac failure acute Cardiac failure chronic Cardiac failure congestive Cardiopulmonary failure Ventricular failure Ischaemic coronary artery disorders *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 6 of 61

7 Report type: Spontaneous Reaction Name Cardiac disorders cont'd Acute coronary syndrome Acute myocardial infarction Angina pectoris Myocardial infarction Myocardial ischaemia Silent myocardial infarction Left ventricular failures Acute left ventricular failure Left ventricular failure Mitral valvular disorders Mitral valve disease Mitral valve incompetence Myocardial disorders NEC Cardiac hypertrophy Cardiomegaly Diastolic dysfunction Dilatation ventricular Left atrial dilatation Left ventricular dysfunction Left ventricular hypertrophy Right ventricular dysfunction Right ventricular hypertrophy Systolic dysfunction Ventricular dysfunction Ventricular hypertrophy Noninfectious myocarditis Myocarditis Noninfectious pericarditis Pericarditis Pericarditis constrictive Pericardial disorders NEC Pericardial effusion Pericardial haemorrhage Rate and rhythm disorders NEC Arrhythmia Bradycardia Extrasystoles Tachycardia Supraventricular arrhythmias Atrial fibrillation Atrial flutter Sick sinus syndrome *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 7 of 61

8 Report type: Spontaneous Reaction Name Cardiac disorders cont'd Sinus arrhythmia Sinus tachycardia Supraventricular extrasystoles Supraventricular tachycardia Tricuspid valvular disorders Tricuspid valve disease Ventricular arrhythmias and cardiac arrest Cardiac arrest Cardio-respiratory arrest Ventricular extrasystoles Ventricular tachycardia Cardiac disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 8 of 61

9 Report type: Spontaneous Reaction Name Congenital disorders Autosomal chromosomal abnormalities Trisomy Haemoglobinopathies congenital Haemoglobinopathy Sickle cell anaemia with crisis Sickle cell trait Thalassaemia beta Congenital disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 9 of 61

10 Report type: Spontaneous Reaction Name Ear disorders Ear disorders NEC Ear disorder Ear pain Hearing losses Deafness Inner ear signs and symptoms Tinnitus Ear disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 10 of 61

11 Report type: Spontaneous Reaction Name Endocrine disorders Anterior pituitary hyperfunction Hyperprolactinaemia Endocrine abnormalities of gonadal function NEC Hypogonadism Posterior pituitary disorders Diabetes insipidus Thyroid disorders NEC Goitre Thyroid hyperfunction disorders Hyperthyroidism Thyroid hypofunction disorders Hypothyroidism Endocrine disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 11 of 61

12 Report type: Spontaneous Reaction Name Eye disorders Blindness (excl colour blindness) Blindness Cataract conditions Cataract Conjunctival and corneal bleeding and vascular disorders Conjunctival pallor Conjunctival infections, irritations and inflammations Conjunctivitis Corneal infections, oedemas and inflammations Ulcerative keratitis Eyelid movement disorders Excessive eye blinking Glaucomas (excl congenital) Glaucoma Ocular disorders NEC Eye disorder Eye pain Ocular icterus Ocular infections, inflammations and associated manifestations Eye pruritus Ocular hyperaemia Ocular nerve and muscle disorders Eye movement disorder Oculogyric crisis Partial vision loss Visual acuity reduced Pupil disorders Miosis Visual disorders NEC Vision blurred Visual impairment Eye disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 12 of 61

13 Report type: Spontaneous Reaction Name Gastrointestinal disorders Abdominal findings abnormal Abdominal mass Abdominal hernias, site unspecified Abdominal strangulated hernia Acute and chronic pancreatitis Pancreatitis Pancreatitis chronic Pancreatitis necrotising Anal and rectal disorders NEC Anal fissure Anal and rectal pains Proctalgia Anal and rectal ulcers and perforation Rectal ulcer Colitis (excl infective) Colitis Colitis ulcerative Dental and periodontal infections and inflammations Dental caries Dental disorders NEC Poor dental condition Tooth disorder Diaphragmatic hernias Hiatus hernia Diarrhoea (excl infective) Diarrhoea Diarrhoea haemorrhagic Duodenal and small intestinal stenosis and obstruction Small intestinal obstruction Duodenal ulcers and perforation Duodenal ulcer Dyspeptic signs and symptoms Dyspepsia Faecal abnormalities NEC Abnormal faeces Faecaloma Flatulence, bloating and distension Abdominal distension Gastric and oesophageal haemorrhages Gastric haemorrhage Gastric ulcers and perforation *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 13 of 61

14 Report type: Spontaneous Reaction Name Gastrointestinal disorders cont'd Gastric ulcer Gastric ulcer perforation Gastritis erosive Gastritis (excl infective) Gastritis Reflux gastritis Gastrointestinal and abdominal pains (excl oral and throat) Abdominal pain Abdominal pain lower Abdominal pain upper Abdominal tenderness Gastrointestinal atonic and hypomotility disorders NEC Constipation Gastric dilatation Gastric hypomotility Gastrointestinal hypomotility Gastrooesophageal reflux disease Infrequent bowel movements Intestinal dilatation Gastrointestinal disorders NEC Food poisoning Functional gastrointestinal disorder Gastric disorder Gastrointestinal disorder Gastrointestinal oedema Intestinal mass Intestinal prolapse Gastrointestinal fistulae Intestinal fistula Gastrointestinal inflammatory disorders NEC Crohn's disease Duodenitis Enteritis Gastrointestinal inflammation Inflammatory bowel disease Gastrointestinal mucosal dystrophies and secretion disorders Barrett's oesophagus Gastrointestinal tract mucosal pigmentation Gastrointestinal necrosis and gangrene (excl gangrenous hernia) Gastrointestinal necrosis Gastrointestinal signs and symptoms NEC Abdominal discomfort *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 14 of 61

15 Report type: Spontaneous Reaction Name Gastrointestinal disorders cont'd Aphagia Dysphagia Faecal incontinence Gastrointestinal spastic and hypermotility disorders Irritable bowel syndrome Gastrointestinal stenosis and obstruction NEC Gastrointestinal obstruction Ileus Intestinal obstruction Gastrointestinal ulcers and perforation, site unspecified Gastrointestinal ulcer Gastrointestinal ulcer perforation Gastrointestinal vascular occlusion and infarction Intestinal infarction Mesenteric artery thrombosis Haemorrhoids and gastrointestinal varices (excl oesophageal) Gastric varices Intestinal haemorrhages Large intestinal haemorrhage Rectal haemorrhage Intestinal ulcers and perforation NEC Intestinal perforation Large intestine perforation Large intestinal stenosis and obstruction Large intestinal obstruction Volvulus Nausea and vomiting symptoms Faecal vomiting Nausea Regurgitation Retching Vomiting Vomiting projectile Non-mechanical ileus Ileus paralytic Non-site specific gastrointestinal haemorrhages Gastrointestinal haemorrhage Haematemesis Haematochezia Melaena Upper gastrointestinal haemorrhage Oesophageal stenosis and obstruction *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 15 of 61

16 Report type: Spontaneous Reaction Name Gastrointestinal disorders cont'd Oesophageal obstruction Oesophageal stenosis Oesophageal ulcers and perforation Oesophageal perforation Oesophageal rupture Oesophageal ulcer Oesophageal varices Varices oesophageal Oesophagitis (excl infective) Oesophagitis Oral dryness and saliva altered Salivary hypersecretion Oral soft tissue signs and symptoms Oral discomfort Pancreatic disorders NEC Pancreatic mass Peptic ulcers and perforation Peptic ulcer Peptic ulcer haemorrhage Peptic ulcer perforation Peritoneal and retroperitoneal disorders Ascites Peritoneal and retroperitoneal fibrosis and adhesions Abdominal adhesions Peritoneal adhesions Peritoneal and retroperitoneal haemorrhages Retroperitoneal haematoma Salivary gland enlargements Parotid gland enlargement Submaxillary gland enlargement Salivary gland infections and inflammations Parotid gland inflammation Stomatitis and ulceration Stomatitis Tongue disorders Tongue ulceration Tongue signs and symptoms Swollen tongue Tooth missing Tooth loss Gastrointestinal disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 16 of 61

17 Report type: Spontaneous Reaction Name General disorders Administration site reactions NEC Vessel puncture site haematoma Adverse effect absent No adverse event Asthenic conditions Asthenia Fatigue Malaise Body temperature altered Hyperthermia Hypothermia Death and sudden death Brain death Cardiac death Death Drowning Sudden death Febrile disorders Hyperpyrexia Pyrexia Feelings and sensations NEC Chills Feeling abnormal Feeling cold Feeling hot Hangover Sensation of foreign body Thirst Fibrosis NEC Fibrosis Gait disturbances Abasia Gait disturbance Loss of control of legs General signs and symptoms NEC Adhesion Apparent death Condition aggravated Crepitations General physical health deterioration Ill-defined disorder *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 17 of 61

18 Report type: Spontaneous Reaction Name General disorders cont'd Influenza like illness Irritability Local swelling Multi-organ failure Obstruction Organ failure Swelling Terminal state Inflammations Inflammation Injection site reactions Injection site haematoma Interactions Alcohol interaction Drug interaction Mass conditions NEC Cyst Mass Nodule Submandibular mass Mucosal findings abnormal Oedema mucosal Oedema NEC Face oedema Generalised oedema Oedema Oedema peripheral Pain and discomfort NEC Chest discomfort Chest pain Facial pain Pain Tenderness Therapeutic and nontherapeutic responses Drug ineffective Drug intolerance Idiosyncratic drug reaction No therapeutic response Therapeutic response decreased Ulcers NEC Ulcer Withdrawal and rebound effects *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 18 of 61

19 Report type: Spontaneous Reaction Name General disorders cont'd Rebound effect General disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 19 of 61

20 Report type: Spontaneous Reaction Name Hepatic disorders Bile duct infections and inflammations Cholangitis Cholecystitis and cholelithiasis Cholecystitis Cholecystitis acute Cholelithiasis Cholestasis and jaundice Cholestasis Jaundice Jaundice cholestatic Gallbladder disorders NEC Gallbladder pain Gallbladder perforation Hepatic and hepatobiliary disorders NEC Liver disorder Hepatic enzymes and function abnormalities Hepatic function abnormal Hepatic failure and associated disorders Acute hepatic failure Hepatic failure Hepatic fibrosis and cirrhosis Hepatic cirrhosis Hepatic vascular disorders Portal hypertension Hepatobiliary signs and symptoms Hepatic congestion Hepatomegaly Hepatocellular damage and hepatitis NEC Alcoholic liver disease Hepatic steatosis Hepatitis Obstructive bile duct disorders (excl neoplasms) Bile duct obstruction Bile duct stone Hepatic disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 20 of 61

21 Report type: Spontaneous Reaction Name Immune system disorders Allergic conditions NEC Hypersensitivity Amyloidoses Amyloidosis Anaphylactic responses Anaphylactic reaction Atopic disorders Seasonal allergy Autoimmune disorders NEC Autoimmune disorder Immune system disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 21 of 61

22 Report type: Spontaneous Reaction Name Infections Abdominal and gastrointestinal infections Abdominal abscess Abscess intestinal Appendicitis Appendicitis perforated Diarrhoea infectious Diverticulitis Gastroenteritis Gastrointestinal infection Infectious peritonitis Rectal abscess Bacterial infections NEC Bacterial infection Cellulitis Gangrene Meningitis bacterial Pneumonia bacterial Bone and joint infections Osteomyelitis Breast infections Breast abscess Caliciviral infections Gastroenteritis norovirus Campylobacter infections Campylobacter infection Candida infections Oral candidiasis Cardiac infections Endocarditis Subacute endocarditis Central nervous system and spinal infections Meningitis Clostridia infections Clostridial infection Dental and oral soft tissue infections Gingival infection Oral infection Parotitis Tooth abscess Tooth infection Ear infections *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 22 of 61

23 Report type: Spontaneous Reaction Name Infections cont'd Ear infection Labyrinthitis Epstein-Barr viral infections Infectious mononucleosis Escherichia infections Escherichia sepsis Eye and eyelid infections Eye infection Female reproductive tract infections Pelvic inflammatory disease Helicobacter infections Helicobacter gastritis Helminthic infections NEC Helminthic infection Hepatitis viral infections Hepatitis B Hepatitis C Hepatobiliary and spleen infections Cholecystitis infective Herpes viral infections Herpes zoster Oral herpes Infections NEC Abscess Empyema Groin abscess Groin infection Infection Localised infection Pelvic infection Post procedural infection Postoperative wound infection Respiratory tract infection Wound infection Influenza viral infections H1N1 influenza Influenza Klebsiella infections Klebsiella bacteraemia Lower respiratory tract and lung infections Bronchitis Bronchopneumonia *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 23 of 61

24 Report type: Spontaneous Reaction Name Infections cont'd Lobar pneumonia Lower respiratory tract infection Lung abscess Lung infection Pneumonia Pneumonia primary atypical Muscle and soft tissue infections Abscess neck Pneumocystis infections Pneumocystis jiroveci pneumonia Retroviral infections HIV infection Salmonella infections Salmonellosis Sepsis, bacteraemia, viraemia and fungaemia NEC Neutropenic sepsis Sepsis Septic shock Urosepsis Skin structures and soft tissue infections Furuncle Impetigo Paronychia Recurring skin boils Skin infection Subcutaneous abscess Staphylococcal infections Staphylococcal infection Wound infection staphylococcal Tuberculous infections Tuberculosis Upper respiratory tract infections Nasopharyngitis Peritonsillar abscess Pharyngitis Rhinitis Tonsillitis Upper respiratory tract infection Urinary tract infections Cystitis Kidney infection Pyelonephritis *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 24 of 61

25 Report type: Spontaneous Reaction Name Infections cont'd Pyelonephritis chronic Urinary tract infection Vascular infections Infusion site infection Viral infections NEC Encephalitis viral Gastroenteritis viral Hepatitis viral Meningitis viral Pneumonia viral Viral diarrhoea Viral infection Viral myocarditis Viral pericarditis Infections TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 25 of 61

26 Report type: Spontaneous Reaction Name Injuries Cardiovascular injuries Aortic injury Eye injuries NEC Eye injury Fractures and dislocations NEC Fracture Joint dislocation Multiple fractures Heat injuries (excl thermal burns) Heat exhaustion Limb injuries NEC (incl traumatic amputation) Joint injury Limb crushing injury Limb injury Lower limb fractures and dislocations Ankle fracture Femoral neck fracture Femur fracture Foot fracture Hip fracture Lower limb fracture Tibia fracture Maladministrations Drug administration error Drug dose omission Incorrect dose administered Wrong drug administered Wrong technique in drug usage process Medication errors NEC Drug dispensing error Medication error Medication errors due to accidental exposures Accidental exposure Non-site specific injuries NEC Accident Fall Foreign body Injury Multiple injuries Road traffic accident Skeletal injury *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 26 of 61

27 Report type: Spontaneous Reaction Name Injuries cont'd Non-site specific procedural complications Post procedural complication Overdoses Accidental overdose Intentional overdose Multiple drug overdose Multiple drug overdose intentional Overdose Pelvic fractures and dislocations Pelvic fracture Poisoning and toxicity Alcohol poisoning Chemical poisoning Poisoning Toxicity to various agents Pregnancy related accidental exposures and injuries Foetal exposure during pregnancy Maternal exposure during pregnancy Radiation injuries Sunburn Site specific injuries NEC Face injury Head injury Neck injury Skin injuries NEC Contusion Laceration Skull fractures, facial bone fractures and dislocations Facial bones fracture Spinal cord injuries NEC Spinal cord injury Spinal fractures and dislocations Dislocation of vertebra Lumbar vertebral fracture Spinal fracture Thoracic vertebral fracture Thermal burns Thermal burn Upper limb fractures and dislocations Hand fracture Humerus fracture Ulna fracture *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 27 of 61

28 Report type: Spontaneous Reaction Name Injuries cont'd Upper limb fracture Wrist fracture Injuries TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 28 of 61

29 Report type: Spontaneous Reaction Name Investigations Autoimmunity analyses Antinuclear antibody positive Antiphospholipid antibodies positive Cardiolipin antibody positive Bacteria identification and serology (excl mycobacteria) Antibiotic resistant Staphylococcus test Blood counts NEC Blood count abnormal Full blood count abnormal Full blood count decreased Full blood count increased Blood gas and acid base analyses Blood ph decreased Carbon dioxide increased Oxygen saturation decreased Bone marrow and immune tissue imaging procedures Bone marrow myelogram abnormal Carbohydrate tolerance analyses (incl diabetes) Blood glucose abnormal Blood glucose decreased Blood glucose fluctuation Blood glucose increased Glycosylated haemoglobin increased Cardiac auscultatory investigations Cardiac murmur Cardiac function diagnostic procedures Echocardiogram abnormal Ejection fraction decreased Cardiac imaging procedures Cardiothoracic ratio increased Cell marker procedures Cell marker increased Prostatic specific antigen increased Chemistry analyses NEC Inflammatory marker increased Cholesterol analyses Blood cholesterol abnormal Blood cholesterol increased High density lipoprotein abnormal High density lipoprotein decreased Low density lipoprotein increased *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 29 of 61

30 Report type: Spontaneous Reaction Name Investigations cont'd Coagulation and bleeding analyses Activated partial thromboplastin time prolonged Bleeding time prolonged Blood fibrinogen increased Coagulation time prolonged International normalised ratio increased Thrombin time shortened Digestive enzymes Blood amylase increased ECG investigations ECG P wave inverted ECG signs of myocardial ischaemia Electrocardiogram PR shortened Electrocardiogram QRS complex prolonged Electrocardiogram QT prolonged Electrocardiogram ST segment abnormal Electrocardiogram ST segment depression Electrocardiogram ST segment elevation Electrocardiogram ST-T change Electrocardiogram T wave abnormal Electrocardiogram T wave amplitude decreased Electrocardiogram T wave inversion Electrocardiogram abnormal Electrocardiogram change Foetal and neonatal diagnostic procedures Foetal heart rate decreased Haematological analyses NEC Red blood cell sedimentation rate increased Heart rate and pulse investigations Heart rate decreased Heart rate increased Heart rate irregular Pulse abnormal Immunoglobulin analyses Blood immunoglobulin A decreased Blood immunoglobulin E increased Blood immunoglobulin M decreased Monoclonal immunoglobulin present Immunology analyses NEC Antibody test positive Investigations NEC Blood test abnormal *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 30 of 61

31 Report type: Spontaneous Reaction Name Investigations cont'd False positive investigation result Quality of life decreased Lipoprotein and lipid tests NEC Lipids abnormal Liver function analyses Alanine aminotransferase Alanine aminotransferase abnormal Alanine aminotransferase increased Aspartate aminotransferase abnormal Aspartate aminotransferase increased Blood bilirubin abnormal Blood bilirubin increased Gamma-glutamyltransferase Gamma-glutamyltransferase increased Hepatic enzyme increased Liver function test abnormal Transaminases increased Metabolism tests NEC Blood ketone body increased Microbiology and serology tests NEC Blood culture positive Mineral and electrolyte analyses Blood bicarbonate increased Blood calcium decreased Blood calcium increased Blood potassium decreased Blood potassium increased Blood sodium decreased Blood sodium increased Serum ferritin decreased Serum ferritin increased Musculoskeletal and soft tissue imaging procedures Spinal X-ray Neurologic diagnostic procedures Coma scale abnormal Past-pointing Positive Rombergism Parathyroid analyses Blood parathyroid hormone increased Physical examination procedures Body temperature decreased Body temperature fluctuation *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 31 of 61

32 Report type: Spontaneous Reaction Name Investigations cont'd Body temperature increased Breath sounds abnormal General physical condition abnormal Respiratory rate decreased Respiratory rate increased Weight decreased Weight increased Pituitary analyses anterior Blood prolactin increased Blood thyroid stimulating hormone increased Platelet analyses Platelet aggregation Platelet count decreased Platelet count increased Protein analyses NEC Blood albumin decreased Blood albumin increased C-reactive protein decreased C-reactive protein increased Globulins increased Protein total decreased Protein total increased Red blood cell analyses Haematocrit decreased Haematocrit increased Haemoglobin abnormal Haemoglobin decreased Haemoglobin increased Mean cell haemoglobin concentration decreased Mean cell haemoglobin concentration increased Mean cell haemoglobin decreased Mean cell haemoglobin increased Mean cell volume Mean cell volume abnormal Mean cell volume decreased Mean cell volume increased Red blood cell count abnormal Red blood cell count decreased Red blood cell count increased Red blood cell elliptocytes present Red blood cell hypochromic morphology present Red cell distribution width increased *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 32 of 61

33 Report type: Spontaneous Reaction Name Investigations cont'd Renal function analyses Blood creatine decreased Blood creatinine increased Blood urea decreased Blood urea increased Glomerular filtration rate decreased Respiratory and pulmonary function diagnostic procedures Total lung capacity decreased Respiratory tract and thoracic histopathology procedures Aspiration tracheal Respiratory tract and thoracic imaging procedures Chest X-ray abnormal Skeletal and cardiac muscle analyses Blood creatine phosphokinase abnormal Blood creatine phosphokinase increased Cardiac enzymes increased Troponin I increased Troponin T increased Troponin increased Therapeutic drug monitoring analyses Antipsychotic drug level above therapeutic Antipsychotic drug level below therapeutic Antipsychotic drug level increased Drug level above therapeutic Drug level decreased Drug level increased Thyroid analyses Thyroid function test abnormal Thyroxine free increased Tissue enzyme analyses NEC Blood alkaline phosphatase Blood alkaline phosphatase increased Blood lactate dehydrogenase decreased Blood lactate dehydrogenase increased Toxicology laboratory analyses Opiates positive Urine amphetamine positive Triglyceride analyses Blood triglycerides increased Urinalysis NEC Blood urine present Nitrite urine present *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 33 of 61

34 Report type: Spontaneous Reaction Name Investigations cont'd Protein urine Urine analysis abnormal Urine colour abnormal Vascular tests NEC (incl blood pressure) Blood pressure abnormal Blood pressure decreased Blood pressure diastolic increased Blood pressure increased Blood pressure orthostatic increased Blood pressure systolic decreased Blood pressure systolic increased Virus identification and serology Hepatitis B virus test positive Hepatitis C virus test positive Vitamin analyses Blood folate decreased Vitamin B12 increased Vitamin D decreased Water and electrolyte analyses NEC Blood electrolytes abnormal Blood electrolytes decreased White blood cell analyses Basophil count increased Differential white blood cell count abnormal Eosinophil count decreased Eosinophil count increased Lymphocyte count abnormal Lymphocyte count decreased Lymphocyte count increased Lymphocyte morphology abnormal Monocyte count increased Neutrophil count Neutrophil count decreased Neutrophil count increased Neutrophil toxic granulation present White blood cell count decreased White blood cell count increased Investigations TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 34 of 61

35 Report type: Spontaneous Reaction Name Metabolic disorders Appetite disorders Decreased appetite Diet refusal Hyperphagia Hypophagia Increased appetite Diabetes mellitus (incl subtypes) Diabetes mellitus Diabetes mellitus inadequate control Gestational diabetes Type 1 diabetes mellitus Type 2 diabetes mellitus Diabetic complications NEC Diabetic complication Diabetic ketoacidosis Disorders of purine metabolism Gout Electrolyte imbalance NEC Electrolyte imbalance Elevated cholesterol Hypercholesterolaemia Fluid intake decreased Fluid intake reduced Fluid intake increased Polydipsia General nutritional disorders NEC Cachexia Malnutrition Obesity Overweight Pica Hyperglycaemic conditions NEC Hyperglycaemia Hyperlipidaemias NEC Hyperlipidaemia Hypoglycaemic conditions NEC Hypoglycaemia Iron deficiencies Iron deficiency Metabolic acidoses (excl diabetic acidoses) Ketoacidosis *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 35 of 61

36 Report type: Spontaneous Reaction Name Metabolic disorders cont'd Metabolic disorders NEC Metabolic disorder Metabolic syndrome Potassium imbalance Hypokalaemia Sodium imbalance Hypernatraemia Hyponatraemia Total fluid volume decreased Dehydration Total fluid volume increased Fluid overload Fluid retention Metabolic disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 36 of 61

37 Report type: Spontaneous Reaction Name Muscle & tissue disorders Arthropathies NEC Arthritis Arthropathy Polyarthritis Bone disorders NEC Bone lesion Exostosis Spinal disorder Bone related signs and symptoms Pain in jaw Joint related signs and symptoms Arthralgia Joint swelling Lupus erythematosus (incl subtypes) Lupus-like syndrome Systemic lupus erythematosus Metabolic bone disorders Osteoporosis Muscle infections and inflammations Myositis Muscle related signs and symptoms NEC Muscle atrophy Muscle spasms Muscle twitching Muscle tone abnormalities Muscle rigidity Muscle weakness conditions Muscular weakness Musculoskeletal and connective tissue infections and inflammations NEC Connective tissue inflammation Musculoskeletal and connective tissue pain and discomfort Back pain Limb discomfort Musculoskeletal pain Pain in extremity Musculoskeletal and connective tissue signs and symptoms NEC Mobility decreased Muscle contracture Musculoskeletal stiffness Posture abnormal Sensation of heaviness *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 37 of 61

38 Report type: Spontaneous Reaction Name Muscle & tissue disorders cont'd Myopathies Rhabdomyolysis Osteoarthropathies Osteoarthritis Psoriatic arthropathies Psoriatic arthropathy Rheumatoid arthropathies Rheumatoid arthritis Soft tissue disorders NEC Axillary mass Neck mass Soft tissue necrosis Spondyloarthropathies Ankylosing spondylitis Muscle & tissue disorders TOTAL *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 38 of 61

39 Report type: Spontaneous Reaction Name Neoplasms Adult T-cell lymphomas/leukaemias Adult T-cell lymphoma/leukaemia Anal canal neoplasms malignant Anal cancer B-cell lymphomas NEC B-cell lymphoma Bladder neoplasms malignant Bladder cancer Breast and nipple neoplasms malignant Breast cancer Carcinoid tumours Carcinoid tumour of the appendix Cardiovascular neoplasms benign Haemangioma Central nervous system neoplasms malignant NEC Brain neoplasm malignant Malignant neoplasm of spinal cord Cervix neoplasms malignant Cervix carcinoma Cervix carcinoma stage Colonic neoplasms malignant Colon cancer Colon cancer stage III Colon cancer stage IV Colorectal and anal neoplasms malignancy unspecified Colon neoplasm Diffuse large B-cell lymphomas Diffuse large B-cell lymphoma Diffuse large B-cell lymphoma stage II Endocrine neoplasms benign NEC Pituitary tumour benign Gastric neoplasms malignant Gastric cancer Gastrointestinal neoplasms malignant NEC Gastrointestinal carcinoma Hepatic neoplasms malignant Hepatic neoplasm malignant Hepatobiliary neoplasms malignancy unspecified Hepatic neoplasm Hodgkin's disease NEC Hodgkin's disease *This provides the number of individual reports and may be less than the sum of the single-active and multi-active columns. For example, if both a single- and multi-active product are considered by the reporter to have a Page 39 of 61