Pharmacovigilance PDF

PHARMACOVIGILANCE LAWRENCE MICAH-AMUAH COURSE OUTLINE Introduction to Pharmacovigilance Importance of Pharmacovigilance The WHO pharmacovigilance programme The Pharmacovigilance process Adverse Drug Reactions (ADRs) Mechanisms of ADRs Clinical management of ADRs What is Pharmacovi...

PHARMACOVIGILANCE LAWRENCE MICAH-AMUAH COURSE OUTLINE Introduction to Pharmacovigilance Importance of Pharmacovigilance The WHO pharmacovigilance programme The Pharmacovigilance process Adverse Drug Reactions (ADRs) Mechanisms of ADRs Clinical management of ADRs What is Pharmacovigilance? Pharmacon (Greek) = Medicinal Substance or Drug Vigilia (Greek) = To keep watch The process of paying close and continuous attention to medicines. WHO DEFINITION The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug related problems. (WHO 2002) PHARMACOVIGILANCE WHAT IS IT? Pharmacovigilance is the process of detecting, evaluating and preventing the adverse effects of medicines. In line with this definition, the objectives of the law and guidelines for pharmacovigilance are: 1. Preventing harm from adverse reactions in humans arising from the use of authorized medicinal products within or outside the terms of marketing authorization or from occupational exposure; and 2. Promoting the safe and effective use of medicinal products, in particular through providing timely information about the safety of medicinal products to patients, healthcare professionals and the public. INTRODUCTION TO PHARMACOVIGILANCE cont Pharmacovigilance is therefore an activity contributing to the protection of patients and public health. PV is also referred sometimes to as “drug safety monitoring” or “post market surveillance” (PMS) though PMS involves more than just pharmacovigilance. PV activities are an essential component of risk management and most risk management plans contain specified activities. SCOPE OF PHARMACOVIGILANCE Pharmacovigilance covers all medical products: Allopathic medicines Herbals, alternate and complementary medicines Vaccines and biologicals, etc. Blood products (haemovigilance) Medical devices AIMS OF PHARMACOVIGILANCE The specific aims of pharmacovigilance are to: 1. improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions, 2. improve public health and safety in relation to the use of medicines, 3. contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use and 4. promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public  The aim and scope of pharmacovigilance is broad and includes multiple components such as: ✓medication errors ✓counterfeit and unauthorized medicines ✓drug interactions and ✓irrational prescription and utilization of medicines.  Many issues are also of relevance to the science of Pharmacovigilance. These include: ✓substandard medicines ✓medication errors ✓lack of efficacy reports ✓use of medicines for indications that are not approved and for which there is inadequate scientific basis ✓case reports of acute and chronic poisoning ✓assessment of drug-related mortality ✓abuse and misuse of medicines ✓adverse interactions of medicines with chemicals, other medicines, and food. The ultimate goals of Pharmacovigilance 1. The rational and safe use of medicines 2. The assessment and communication of the risks and benefits of drugs on the market 3. Education and informing of patients/consumers IMPORTANCE OF PHARMACOVIGILANCE Pharmacovigilance and all drug safety issues are relevant for everyone whose life is touched in any way by medical interventions. A healthcare system that includes pharmacovigilance: ✓promotes the safety of medications by minimizing Adverse Drug Reactions occurrence and ✓provides a warning network of various healthcare providers, regulators, manufacturers and consumers to take remedial actions in a timely and orderly manner. Stake holders in Pharmacovigilance PATIENTS Doctors Pharmacists Nurses Other Health professionals Administrators Pharmaceutical industry Journalists Stake holders in Pharmacovigilance cont… Policy makers Politicians National government Civil society Local and international NGOs International organizations like WHO, UNICEF, USAID, etc. Everyone A BRIEF HISTORY Single most important event : THALIDOMIDE SAGA Thalidomide was introduced as a hypnotic and for prevention of nausea and vomiting in pregnancy -1957 Was marketed as a safe drug for pregnancy. Used for treating anxiety and morning sickness By 1960, it was widely marketed in 46 countries In 1960, first reports of deformed infants (phoecomelia) Phocomelia is a rare congenital anomaly where the proximal aspect of an extremity is absent with the hand or foot attached directly to the trunk A BRIEF HISTORY The first time the link between thalidomide and its impact on development was made public was in a letter published in The Lancet from an Australian doctor William McBride, in 1961. The drug was formally withdrawn by Chemie Grünenthal on 26 November 1961 and a few days later, on 2 December 1961, the UK distributors followed suit. However, it remained in many medicine cabinets under many different names. Withdrawn in 1965 by most countries Withdrawal from the Market as a result of Pharmacovigilance reporting DRUG REASON FOR WITHDRAWAL YEAR OF YEAR OF APPROVAL WITHDRAWAL Practolol Blindness 1970 1975 Benoxaprofen Onycholysis, liver, renal and 1982 1982 bone marrow toxicity Encainide Excessive mortality 1987 1991 Temafloxacin Haemolytic Anaemia, liver and 1992 1992 kidney failure Bromfenac Serious Hepatotoxic Effect 1997 1998 Phenformin Associated lactic acidosis 1960 1977 WHY SHOULD A NURSE BE INTERESTED IN PHARMACOVIGILANCE? Primum non nocere… As a nurse; Before you care for your patient…… Before you administer any therapy ………… Before you relay any information to a patient in a form of counselling …….. Before any action or procedure performed ………… WHY SHOULD A NURSE BE INTERESTED IN PHARMACOVIGILANCE? 1. Humanitarian concern - Insufficient evidence of safety from clinical trials 2. Ethics - “Dying from a disease is sometimes unavoidable; dying from a medicine is unacceptable” – Lepakhin V. Geneva (2005) 3. Medicines are supposed to be beneficial and not harmful 4. Adverse drug reactions are expensive 5. Promoting rational use of medicines and adherence 6. Ensuring public confidence LIMITATIONS OF CLINICAL STUDY DATA CLINICAL TRIALS CLINICAL PRACTICE Number of Patients Hundreds (rarely Thousands to millions thousands) Duration Weeks to months Years Population Pregnant women, children All and elderly are excluded Concomitant Avoided Usually present Medication/Illness Dose Fixed Variable (compliance) Conditions Rigorous; more Flexible; less information information Further Reading Read on Clinical Trials The role of nurses in Pharmacovigilance and Drug Safety Nurses use their knowledge and experience to identify and assess events for safety reporting, thereby increasing both the consistency and quality of the safety data that is reported to the FDA both locally and globally. The nursing education and background really puts nurses in a unique position to understand the importance of reporting adverse events. As nurses and patient advocates, we are obliged to REPORT suspected adverse drug reactions noted when providing care. THE WHO PHARMACOVIGILANCE PROGRAMME WHO and UMC Uppsala Monitoring Centre (UMC) is a field name of the WHO collaborating Centre for International Drug Monitoring It is responsible for the management of the WHO program for International Drug Monitoring UMC is based in Uppsala, Sweden THE WHO PHARMACOVIGILANCE PROGRAMME The main objective of the WHO programme is TIMELY identification of drug safety signals to prevent another thalidomide tragedy. This is only achieved if information is collected, processed and submitted quickly and efficiently. Nurses have a key role in all aspects of this programme. THE WHO PHARMACOVIGILANCE PROGRAMME UMC works by collecting, assessing and communicating information from member countries' national pharmacovigilance centres in regard to the benefits, harm, effectiveness and risks of drugs. Identification and analysis of new adverse reaction signal from the case report information submitted to the National Centres and from them to the database. UMC is involved in information exchange between WHO and national centres, mainly through ‘Vigmed’ Also involved in periodical newsletters, guidelines and books in pharmacovigilance and risk management Provision of training and consultancy support to national centres and countries establishing pharmacovigilance systems. Collaborate with member countries in the development of the science of pharmacovigilance PHARMACOVIGILANCE PROCESS Simply refers to the drug safety monitoring process Pharmacovigilance is not a simple process It is a complex system that allows all parties in drug development, marketing and usage (administration) to ensure the medicinal product’s safety. The exchange of such data is a complex process involving multiple stages THE PHARMACOVIGILANCE PROCESS PHARMACOVIGILANCE PROCESS The pharmacovigilance process consists of 4 stages 1. Detection 2. Assessment 3. Understanding 4. Prevention of Adverse Effects PHARMACOVIGILANCE PROCESS PHARMACOVIGILANCE PROCESS Stage 1. DETECTION Collection of Individual Case Safety Reports (Detecting and Reporting ADR) Pharmacovigilance starts with safety information that comes from different sources such as solicited and unsolicited reporting. The reports may be classified as: ✓Mandatory (Solicited) ✓Spontaneous (Unsolicited) PHARMACOVIGILANCE PROCESS SOLICITED SOURCES (Mandatory) Received as a result of targeted data collection Examples include: ✓Clinical Trials ✓Registries ✓Personalized programmes for non-registered drug administration PHARMACOVIGILANCE PROCESS UNSOLICITED SOURSES (Spontaneous) Received without request Examples include: ✓Consumers and Patients (regardless of medical confirmation) ✓Healthcare Professionals ✓Regulatory Authorities ✓Literature reports ✓License partners ✓Lawsuits against medicinal product: Legal cases ✓Internet and other media sources PHARMACOVIGILANCE PROCESS Stage 2. Assessment After collection of an adverse event, an assessment of the ICSR is performed Steps involved in the assessment include: A. Triage – establishing the validity of an ICSR. A valid ICSR should mandatorily possess ✓An identifiable patient ✓An identifiable reporter ✓A suspect drug ✓An adverse event PHARMACOVIGILANCE PROCESS B. Data Entry After case validation, the safety associate enters the safety information into the safety database. The further process in data entry includes: ✓Seriousness determination ✓Coding of adverse events using MedDRA ✓Causality assessment ✓Labelling assessment ✓Clear and concise narrative writing PHARMACOVIGILANCE PROCESS C. Query Process It involves the raising of queries to the reporter if any additional information is required and also to clarify the discrepancies (if any) in the safety data D. Medical Input/Review Safety Physician reviews safety information with emphasis on causality and seriousness, and provides pharmacovigilance comments E. Case Closure The completed report is submitted to the respective regulatory authorities PHARMACOVIGILANCE PROCESS Stage 3 Understanding the drug safety profile Aggregate data review is performed to understand the drug safety profile using the following documents: ✓Periodic Benefit-Risk Evaluation Report (PBRER) ✓Specific adverse reaction follow-up questionnaires ✓Signal Analysis ✓Risk Management Plan (RMP) ✓Development Safety Update Report (DSUR) PHARMACOVIGILANCE PROCESS Stage 4 Prevention of Adverse Effects Action is taken to prevent the Adverse drug reaction from recurring by: ✓Performing Risk Minimization Activities i.e. to update the Summary of Product Characteristics Patient Information leaflet Labelling Packaging of the medicine Legal status of the medicine ✓Monitoring Risk Minimization Activities ADVERSE DRUG REACTIONS (ADRs) ADVERSE DRUG REACTION (ADR) This is a response to a medicine which is noxious and unintended, and which occurs at doses normally used in human beings. HOW DO WE IDENTIFY ADRs Signs and Symptoms Consider all drugs (medicines) being taken Timing of ADR ✓did it start after the administration of medicine or not ✓Did it occur within the time period of starting the medicine? YES or No Is it an allergy? Consider withdrawal reactions Neoplasms: several years Background of medicine/history SOME TERMINOLOGIES ADVERSE REACTION/ADVERSE EVENT This is characterized by the fact that a causal relationship between a medicinal product and an occurrence (event) is suspected. This implies there is at least a reasonable possibility of a causal relationship between a suspected medicinal product and an adverse event. SERIOUS ADVERSE EVENT (SAE) Any adverse event which is fatal, life-threatening, permanently disabling or which results in hospitalization. SOME TERMINOLOGIES ADVERSE DRUG EVENT “any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment” (WHO definition, 2005) SIDE EFFECT Any unintended effect of a pharmaceutical product occurring at doses normally used by the patient which is related to the pharmacological properties of the drug SOME TERMINOLOGIES DRUG INTERACTIONS This is the alteration of the pharmacological activity of one drug by the concomitant use of another drug or by the presence of some other substances or disease Examples Drug –drug eg. Oral Quinolones and Heamatinics Drug –food eg. Warfarin and Green leafy vegetables Drug –disease eg. Some drugs (eg. Quinine and G6PD) Drug -route of administration eg.: IM diclofenac and Intravenous administration Drug laboratory results eg. Patients on Cephalosporins and serum creatinine Drug co-morbidity : eg. SEVERE ASTHMA and NSAIDs for pain management. This interactions can be Pharmacokinetic or Pharmacodynamic interactions. ADVERSE DRUG REACTION (ADR) ADVERSE DRUG REACTION “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” (WHO definition, 2005) The basic requirements for an ADR are therefore: ✓The reaction is directly related to the drug ✓The drug was being used correctly and appropriately ✓The reaction is harmful TYPE OF ADRS Rawlins MD: BMJ; 1981,282: 974-976 TYPE A-Pharmacological TYPE B-Idiosyncratic TYPE C –Statistical TYPE OF ADRS B. Edward and Aronson, Lancet 2000: 356: 1255 -1259 There are six classes namely; A – Augmented B – Bizarre C – Continuing or Chronic D –Delayed E –End of use F -Failure TYPE OF ADRS and FEATURES A – AUGMENTED Dose related, related to the pharmacology of drug Predictable Low mortality Example: sedation, constipation, diarrhoea, hypoglycemia, hypokalaemia, baldness B – BIZARRE Non dose related Uncommon Not related to pharmacology Unpredictable High mortality Examples: Anaphylaxis, Stevens Johnsons syndrome, blood dyscrasias, hepatitis TYPE OF ADRS and FEATURES C – CONTINUING OR CHRONIC Dose –related and time-related Uncommon Related to the cumulative dose Examples: Thromboembolic events, GI haemorrhage, pancreatitis, adrenal suppression with steroids and osteoporosis with steroids D – DELAYED Time related Uncommon Usually dose related Occurs or becomes apparent sometimes after use of the drug Examples: tardive dyskinesia from antipsychotics TYPE OF ADRS and FEATURES E– END OF USE Withdrawal End of use Examples: Opiate withdrawal symptoms, hypertension after stopping clonididne F – FAILURE Unexpected failure of therapy Common Dose related Often caused by drug interactions Others: adherence to therapy, medication errors Example: the decreased effect of antibiotics due to resistance. In Summary An adverse drug event occurs during drug therapy but does not necessarily have any causal relationship with the drug, whereas an adverse drug reaction is directly related to the drug and occurs in the course of its appropriate use. Drug reactions may be classified as: Type A: Dose-related reactions (adverse effects at either normal dose or overdose), eg. serotonin syndrome or anticholinergic effects of tricyclics Type B: Non-dose-related reactions (i.e. any exposure is enough to trigger such a reaction), eg. allergic or anaphylaxis reactions Type C: Dose and time-related reactions, eg due to dose accumulation, or with prolonged use (eg. adrenal suppression with corticosteroids) Type D: Time related reactions, i.e. due to prolonged use in a drug which doesn't tend to accumulate (eg. tardive dyskinesia from antipsychotics) Type E: Withdrawal reactions, i.e. the undesired effects of ceasing the drug (for example, opiate withdrawal) Type F: Unexpected failure of therapy, where a drug undesirably increases or decreases in efficacy- for example, the decreased clearance of a drug by dialysis, or the decreased effect of antibiotics due to resistance. SEVERITY OF ADRs Minor – no need of therapy, antidote or hospitalization Moderate – requires drug change, specific treatment or hospitalization Severe – potentially life threatening, permanent damage, and prolonged hospitalization Lethal – directly or indirectly lead to death REPORTING OF ADVERSE DRUG REACTIONS A regional or country-wide system for the reporting of suspected adverse drug reactions exist for member countries of WHO. In Ghana, FDA is the agency mandated to receive, process and forward ADRs to UMC. Spontaneous reporting of ADRs is currently the major source of information in pharmacovigilance. The report of an ADR is seen as a case report CASE REPORT: a notification relating to a patient with an adverse medical event (or laboratory test anomaly) suspected to be induced by a medicine ADR Reporting Form A case report should contain information on the following elements 1. The Patient: name (in initials), age, sex, and brief medical history (when relevant) 2. Adverse Event: description (nature, localization, severity, characteristics), results of investigations and tests, start date, course and outcome 3. Suspected Drug(s): name (brand, active ingredient and manufacturer, batch number), dose, route, start/stop dates, indications for use 4. All other drugs used (including self-medication): names, doses, routes, start/stop dates. 5. Risk factors: e.g. impaired renal function, liver function, previous exposure to suspected drug, previous allergies, social drug use 6. Name and address of reporter: to be considered confidential and to be used only for data verification, completion and case follow-up FDA ADR form ONLINE APPS WHO MEDICINE SAFETY CHECKER  WHO CAN REPORT? Any healthcare professional WHERE TO REPORT ADR forms are available at the Pharmacy department and consulting rooms. They can be filled and co-signed with a medical doctor and submitted to the Pharmacy Unit for onward submission to the regional and national FDA offices Advice about Reporting ADRS Report adverse experiences with medications Report serious adverse reactions. A reaction is serious when patient outcome is: ✓Death ✓Life-threatening (real risk of dying) ✓Hospitalization (initial or prolonged) ✓Disability (significant, persistent or permanent) ✓Congenital anomaly ✓Required intervention to prevent permanent impairment or damage Report even if: ✓You are not certain the product caused adverse reaction ✓You don’t have all the details MANAGEMENT OF ADVERSE DRUG REACTIONS Further reading and Group Discussion  THANK YOU FOR YOUR ATTENTION