Pharmacovigilance_a7141d49218606fc01d68c2be045bc12.pptx

pharmacovigilance of drugs

1. Pharmacovigilance

2. Pharmacovigilance The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. activities relating to the detection, assessment

3. Pharmacovigilance Center collects, records, codes ADEs / ADRs analyses and assesses the reports promotes the safe use of drugs creates appropriate structures and means of communication needed to perform its tasks

4. Aims of Pharmacovigilance 1. to improve patient care and safety 2. to improve public health and safety 3. to contribute to the assessment of benefit, harm, effectiveness and risk of medicines 4. to promote education and clinical training 5. to promote effective communication to the public 6. to promote rational and safe use of medicines

5. Adverse Drug Reaction ( WHO ) 'A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function‘. Adverse Event (or Adverse Experience) Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

6. Serious Adverse Drug Reaction A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose: Results in death, Is life-threatening, NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect.

7. Pharmacovigilance process Detecting and reporting ADRs ADRs form is filled out with the patient and reaction details, this later forms basis for data entry Spontaneous Reporting Mandatory Reporting

8. Leading role of spontaneous reporting: Covers all drug use of all populations

9. Minimum requirements for a functional national pharmacovigilance system System is organized and coordinated by the Ministry of Health , academic institutions and hospitals 1- Designated staff (at least one full time), stable basic funding, clear mandates, well defined structures and roles and collaborating with the WHO Programme for International Drug Monitoring 2- The existence of a national spontaneous reporting system with (ADR)reporting form 3- A national database or system for collating and managing ADR reports

10. Minimum requirements for a functional national pharmacovigilance system 4- A national ADR or pharmacovigilance advisory committee provide technical assistance on causality assessment, risk assessment, risk management, case investigation and, where necessary, crisis management including crisis communication 5- A clear strategy for routine and crisis communications endent legally-recognized organizations

11. How to improve Spontaneous Reporting Systems? Regionalisation Combination with DIC-activities Retrieval of additional information Access to all relevant pre- and post-marketing information Access to detailed drug utilization data Standardized Assessment of causality and seriousness Stimulation

12. Expected and Unexpected Events Expected are those adverse events that were observed during clinical trials or post-approval observations and are mentioned in Summary of Product Characteristics (SPC) ‏ Unexpected are those adverse events that were not previously observed and are not documented (in SPC) ‏ Based on frequency of occurrence there are following categories of adverse events:

13. Types of Adverse Reactions (Rawlins and Thompson Classification) ‏ Type A Effects (“Augmented”) ‏ Due to pharmacological effects Are dose related – may often be avoided by using doses which are appropriate to the individual patient Are common, can be experimentally reproduced, known before marketing Example: hypnotic effect after H2 antihistaminics

14. Types of Adverse Reactions (Rawlins and Thompson Classification) ‏ Type B Effects (“ Bizzar ”, idiosyncratic reactions) ‏ Generally rare and unpredictable Little or no dose relationship, not related to drug pharmacodynamics Occur in predisposed, intolerant patients – can be explained by rare genetic polymorphism, allergic reactions Example: Penicilline allergies

15. Types of Adverse Reactions (Rawlins and Thompson Classification) ‏ Type C Effects (“Continuous”) ‏ Adverse reactions after long term therapy There is often no suggestive time relationship and the connection may be very difficult to prove. The use of a drug increases the frequency of “spontaneous” disease Example: carcinogenesis

16. Types of Adverse Reactions (Rawlins and Thompson Classification) ‏ Type D Effects (“Delayed”) ‏ Adverse effect may be presented years after a drug was used Example: Vagina cancer of daughters when their mother was treated by diethylstilbestrol Type E Effects (“Ending”) ‏ Absence of drug after withdrawal – rebound effect Example: corticosteroids in asthma treatment

17. Causality Assessment To determine likelihood of a causal relationship between drug exposure and adverse events it is necessary to evaluate Association in time/place between drug use and event Pharmacology (including current knowledge of nature and frequency of adverse reactions) ‏ Medical or pharmacological plausibility (signs and symptoms, tests, pathological findings, mechanism) ‏ Likelihood or exclusion of other causes

18. Causality Assessment There are more assessment scales for causality evaluation which include: Karch and Lasagna scale Naranjo scale WHO probability scale Jones scale

19. Naranjo scale

20. Pharmacology in Adverse Reactions Detailed safety profile of a drug can only be evaluated and described on base of clinical research and postmarketing surveillance However, there are some factors that can be associated with higher safety risks. These risk can be on side of: Administered drug Patient Environment (xenobiotics, physical conditions) Higher safety risks are associated with medicines with no specific mechanism of action such as neuroleptics (haloperidol, chlorpromazine), non-selective cyclooxygenase inhibitors, cytostatics , morphine analgesics Another group is medicines with narrow therapeutic range (i.e. low therapeutic index) – cardiac glycosides, aminoglycoside antibiotics (gentamycin), theophylline Therapeutic index = Median Toxic Dose (TD50)/ Median Effective Dose (ED50) ‏

21. Risks dependent on Patient Kidney insufficiency – failing excretion of drugs/active metabolites Liver disease – failing drug metabolism Polymorbidity – combination of factors such as drug interactions, multi-organ injury Immunocompetence – higher doses of some drugs (antibiotics) may be needed in decreased immune response New born age – drug metabolizing systems are not fully developed Allergies – risk of drug allergies is higher in patients with already suffer from another allergy Some specific diseases – such as contraindication of beta blockers in asthma

22. Risks dependent on Other Factors Drug dependent Drug interactions Environment dependent Xenobiotics (pesticides, veterinary antibiotics) can interact with drugs metabolism, most commonly on CYP 450 level

23. Steps for Reporting

24. International Cooperation in Drug Safety WHO Monitoring Centre in Uppsala Established in 1978 Coordination of the WHO programme for International Drug Monitoring Collection, processing of data, Education, Research

25. Who Should Report Safety Data Physicians Pharmacists Pharmaceutical companies qualified persons – ( Pharmacovigilence /Regulatory manager) ‏ Investigational products (clinical trials) ‏ Post-approval reporting – Individual Case Safety Report (ICSR), Periodic Safety Update Report (PSUR) ‏ In many countries patients are encouraged (but not obligated) to report side effects

26. What to Report – WHO recommendations Every single problem related to the use of a drug, because probably nobody else is collecting such information All suspected adverse reactions ADRs associated with radiology contrast media, vaccines, diagnostics, drugs used in traditional medicine, herbal remedies, cosmetics, medical devices and equipment Lack of efficacy and suspected pharmaceutical defects Counterfeit pharmaceuticals Development of resistance

27. How to Report - UK “ YellowCard Scheme” - established in 1964 MHRA operates site http://yellowcard.mhra.gov.uk/ for reporting of adverse drug reactions Reporting by post is also possible Both patients and healthcare professionals are encouraged to report all suspected adverse drug reaction. MHRA evaluates whether risk is serious and whether there is a causality. Pharmacies are encouraged to display poster on YellowCard and mention it to patients who may experience ADRs when giving advice MHRA provides yellow card to patients (distributed also thru pharmacies) with information on reporting. Pharmacists are considered to be crucial in informing patients on ADRs reporting

28. Content of Report (MHRA recommendations) ‏ The symptoms or a description of a side effect Information about the person who experienced the side effect (as a minimum, their initials, sex, and age at the time of side effect) ‏ The name of the medicine(s) thought to have caused the side effect The name and full address of the reporter so that the report can be acknowledged and contact made for further information, if necessary.

29. Reporting Requirements for Marketing Authorization Holders (Pharmaceutical Companies) ‏ The Marketing Authorization Holder (MAH) should ensure that h has an appropriate system of pharmacovigilance in place in order to assume responsibility and liability for his products on the market and to ensure that appropriate action may be taken when necessary. MAH should therefore ensure that all information relevant to the risk-benefit balance of a medicinal product is reported to the Competent (Regulatory) Authorities and European Medicines Agency fully and promptly in accordance with the legislation Qualified Person Responsible for Pharmacovigilance MAH submit Periodic Safety Update Report (PSUR) for drugs marketed for less than five years. Submitted in 6 months intervals after MA, once per year two years after MA, then 3-yearly intervals or upon request of regulatory authority

30. Case Study Olanzapine , atypical antipsychotic, indicated for treatment of schizophrenia or bipolar disorder First approved in 1996 by FDA Used for depression, dementia or anxiety In 2004, Committee on safety of medicine issued a warning for not prescribing to elderly patients with dementia Risk of stroke