Questions and answers on serious non-fatal adverse events and reporting rules

Transcription

1 18 April 2013 EMA/CVMP/PhVWP/303762/2012 Committee for Medicinal Products for Veterinary Use Questions and answers on serious non-fatal adverse events and reporting rules This question and answer document was developed to enable all stakeholders understand what constitutes a serious non-fatal adverse event following use of a veterinary medicinal product (VMP), after recommended or non-recommended use. The document provides guidance on which clinical signs or events should be considered as life-threatening or should be considered as resulting in persistent or significant disability or incapacity or congenital anomaly or birth defect. Some clinical signs may vary according to species. This question and answer document also provides information on serious adverse event reporting and complements the guidance included in Volume 9B of The Rules Governing Medicinal Products in the European Union Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use. 1. What is life-threatening in the context of a serious adverse event? A life threatening adverse event is one in which the animal was at risk of death at the time of the event. 2. What is persistent or significant disability in this context? Disability in this context occurs when an animal or group of animals is unable to accomplish elementary every-day activities. Significant disability also occurs in cases when a veterinarian considers it necessary to administer veterinary medicinal products that would not normally be used as a treatment of first choice e.g. corticosteroids in order to stop escalation or worsening of clinical signs. If treatment is successful and clinical signs of the adverse event are not exacerbated or do not last long, this will also be considered as significant disability. 3. How should (fatal and non-fatal) serious adverse events be reported? Serious fatal or non-fatal adverse events should be reported in an expedited manner. 4. What are the examples of serious non-fatal adverse events? 1. There are clinical signs that should automatically lead to classification as serious adverse events as soon as they are reported, regardless of the causality assessment, the outcome, the time to onset etc. (= if it is mentioned, then the adverse event is serious). 7 Westferry Circus Canary Wharf London E14 4HB United Kingdom Telephone +44 (0) Facsimile +44 (0) [email protected] Website An agency of the European Union

2 Some examples are provided below, however please note that this list is not exhaustive: - Shock (all shock reactions, whatever the origin is: circulatory, anaphylactic etc.). Clinical signs of anaphylaxis may vary according to species. For anaphylactic shock, see Table 1 - Respiratory distress, dyspnoea, apnoea - Collapse, syncope - Convulsions - Blindness - Deafness - Paralysis, paresis - Failures of vital organs (total loss of function) - Uterine haemorrhage, uterine rupture, or pyometra - Peritonitis - Diabetes mellitus - Severe fish body deformities - Malignant neoplasia (including sarcomas at administration sites) - Congenital anomaly or birth defect (excluding dew claws). 2. Clinical signs or reactions that could be considered serious or non-serious depending on other criteria such as: Systemic sequelae - Duration - Depth, extent, localisation of lesions - Physiological context (age of the animal, gestation etc.) - Any other information that could make the assessor think what is reported in the adverse event is a life-threatening situation, or a persistent or significant disability/incapacity. Here are some examples: - Facial oedema/angioedema or Quincke s oedema: consider if dyspnoea is associated or if serious oedema has also been detected (pulmonary, laryngeal etc.) - Metabolic and/or endocrinological disorders (elevated renal parameters or liver enzymes etc.): clinical importance has to be considered - Haematological disorders: clinical importance has to be considered - Cardiac arrhythmia: consider clinical importance (syncope, fatigue etc.) - Gastro-enteritis - Reduced mobility (lameness, decubitus): systemic signs, duration to be considered - Injection and application site reaction: systemic signs, localisation, depth and extent of lesions and/or reduced mobility to be considered - Acute mastitis with systemic signs or recumbency - Metritis - Photosensitisation: systemic signs, localisation, depth and extent of lesions to be considered EMA/CVMP/PhVWP/303762/2012 Page 2/6

3 - Pemphigus foliaceous: systemic signs, localisation, depth and extent of lesions to be considered - Pancreatitis: systemic signs to be considered - Significant reduction in physiological function occurring and lasting for a longer period e.g. persistent anorexia, reduced milk yield, reduced egg production, reduced growth rate - Lack of expected efficacy: if the lack of expected efficacy results in a life-threatening condition, or in persistent or significant disability/incapacity of the animal or the group of animals. EMA/CVMP/PhVWP/303762/2012 Page 3/6

4 Table 1 Clinical signs of anaphylactic shock reactions in different species Anaphylactic shock is an acute allergic, potentially life-threatening, Type 1 hypersensitivity reaction resulting from the generalised release of potent vasoactive substances from mast cells and basophils. The clinical signs of anaphylaxis can vary depending on the major so-called shock organ relevant to the species. The table below summarises the differences between species. Species Major shock organ(s) Pathology Clinical signs VeDDRA 1 low level term (LLT code) Dogs Liver Hepatic and intestinal engorgement, visceral haemorrhage. Initially excitement, urticaria, angioedema and pruritus, then vomiting and defecation. Finally collapse, dyspnoea and convulsions. Excitation (120) Hyperexcitation (122) Agitation (121) Facial oedema (1110) Allergic oedema (320) Lip oedema (1577) Angioedema (516) Quincke s oedema (1111) Skin oedema (968) Oedema NOS (609) Localised oedema (not application site) (1586) Conjunctival oedema (1108) Urticaria (521) Vomiting (334) Emesis (multiple) (2082) Emesis (335) Involuntary defecation (270) Convulsion (642) Cats Gastrointestinal tract Bronchoconstriction, pulmonary haemorrhage, oedema and emphysema, oedema of the glottis. Initially angioedema and pruritus around the face, then salivation, dyspnoea, vomiting, incoordination and collapse. Angioedema (516) Face and neck swelling (see also 'Skin') (1462) Facial oedema (1110) Facial swelling (see also 'Skin') (517) Lip oedema (1577) Swollen face (see also 'Skin') (1811) Swollen lip (see also 'Skin') (1817) Allergic oedema (320) Scratching (959) 1 VeDDRA: veterinary dictionary for drug related affairs EMA/CVMP/PhVWP/303762/2012 Page 4/6

5 Species Cats cont. Major shock organ(s) Pathology Clinical signs VeDDRA 1 low level term (LLT code) Hypersalivation (293) Increased salivation (1533) Emesis (335) Emesis (multiple) (2082) Vomiting (334) Incoordination (1901) Horses Gastrointestinal tract Pulmonary oedema and emphysema, intestinal oedema and haemorrhage. Initially shivering, sweating and incoordination. Possibly coughing, dyspnoea and diarrhoea. Finally collapse. Shivering (1905) Excessive sweating (1453) Heavy sweating (1519) Increased sweating (974) Incoordination (1901) Cough (884) Diarrhoea (302) Cattle and sheep Pulmonary haemorrhage, oedema and emphysema. Initially urticaria, angioedema, pruritus and restlessness. Coughing, severe dyspnoea and cyanosis. Also defecation, urination and bloat. Urticaria (521) Angioedema (516) Scratching (959) Restlessness (119) Cough (884) Cyanosis (1009) Involuntary defecation (270) Urination (1161) Ruminal bloat (320) Pigs Gastrointestinal tract Pulmonary oedema and emphysema, intestinal oedema and haemorrhage. Dyspnoea, cyanosis, pruritus and collapse. Cyanosis (1009) References 1. European Commission (2011) Volume 9B - Pharmacovigilance for Medicinal Products for Veterinary Use Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use 2. European Parliament and the Council. Directive 2001/82/EC of 6 November 2001 on the Community Code Relating to Medicinal Products for Veterinary Use, as amended by Directives 2004/28 EC, 2009/9/EC and 2009/53/EC in European Commission: The Rules Governing Medicinal EMA/CVMP/PhVWP/303762/2012 Page 5/6

6 Products in the European Union Volume 5 EU pharmaceutical legislation for medicinal products for veterinary use ( 3. European Parliament and Council (2004) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. EMA/CVMP/PhVWP/303762/2012 Page 6/6