Pharmacovigilance : Ensuring the Safe Use of Medicine and Role of Pharmacists

1. Pharmacovigilance : Ensuring the Safe Use of Medicine and Role of Pharmacists Fuziah Abdul Rashid Ketua Penolong Pengarah Biro Pengawalan Farmaseutikal Kebangsaan

2. REGISTRATION CRITERIA QUALITY EFFICACY SAFETY

3. Registration Criteria Efficacy Evaluated from data obtained from clinical trials Quality Compliance to established standards, manufacture by GMP licensed premise Safety ** Toxicology, clinical trials ** (Very limited information) (Further established through post registration studies) (Discovering new dangers of drugs after marketing is common)

4. WHAT IS PHARMACOVIGILANCE (PV)? The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem - WHO

5. WHY PV IS NEEDED

6. HISTORY�.. Registration of New Chemical Entities was very much dependant on the status of products in the reference countries Changes to product information was mainly industry driven Few pre-clinical studies conducted in the region and hardly any Phase IV studies Adverse drug reaction reporting was very minimal and mainly involved reports submitted by health care professionals

7. CONT��. Most reports were for known reactions involving older drugs which were used in government-run hospitals Signal detection not possible as there were too few reports Only able to detect some quality defects of generics which manifested as ADRs Pharmacovigilance was mainly about getting ADR reports and submitting them to WHO No significant regulatory changes made based on these reports

8. CURRENT SCENARIO Increased awareness and interest amongst doctors and pharmacists to report ADRS as they have seen some benefit in reporting Increasing number of clinical trials being conducted especially in Singapore, Thailand and Malaysia GCP training for investigators served to increase awareness of SAE and ADR reporting amongst health care professionals and the industry

9. CONT�.. More hospitals and companies using on-line reporting system � less hassle than submitting hard copy reports Increasing involvement by hospital pharmacists in pharmacovigilance � during clinical ward rounds and when counseling patients

10. The Aims of Pharmacovigilance To improve patient care and safety To improve public health and safety To contribute to the assessment of benefit, harm, effectiveness and risk of medicines To promote understanding, education and clinical training

11. Who are the partners? Government Industry Hospitals and academia Medical and pharmaceutical associations Poisons information centres Health professionals Patients Consumers Media WHO

12. DEFINITION Adverse Drug Reaction "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 modification of physiological function." Adverse 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 Side Effect Any unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug

13. WHAT TO REPORT? SERIOUS ADRS A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization of prolongation of existing hospitalization, is a congenital anomaly/birth defect. 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 was more severe.

14. Adverse Reactions:Possible Causes Intrinsic factors of the drug Pharmacological Idiosyncratic Carcinogenicity, Mutagenicity Teratogenicity Extrinsic factors Adulterants Contamination Underlying medical conditions Interactions Wrong usage

15. WHAT SHOULD BE REPORTED New drugs Report all suspected reactions including minor ones For established or well known drugs All serious, unexpected, unusual ADRs Change in frequency of a given reaction ADRs to generics not seen with innovator products ADRs to traditional medicines

16. WHAT SHOUD BE REPORTED All suspected drug-drug, drug-food, drug-food supplement interactions Statement highlighting marine source of supplements such as glucosamine so that can be avoided by those with allergy to sea food ADRs associated with drug withdrawals ADRs due to medication errors eg vincristine given IT ADRs due to lack of efficacy or suspected pharmaceutical defects

17. INNOVATOR PRODUCTS Limited information available at time when drug is first marketed Minimal information on use in Asian population, interactions with indigenous medicines Conduct intensive monitoring to identify new, unlabeled adverse reactions, monitor for �rare� reactions Provide updates to prescribers on new findings, labelling changes, safety issues

18. GENERIC PRODUCTS Monitor efficacy Monitor adverse effect profile to study differences in ADR pattern c.f innovator products Help in improving quality of generics used

19. NON-PRESCRIPTION MEDICATIONS Quality defects can also lead to ADRs e.g. Pan Pharmaceuticals (Australia) case Patients can develop ADRs to food supplements, �health products� Overuse of supplements Current issue of dioxin contamination in Cod Liver Oil preparations resulting in product withdrawals in UK

20. TRADITIONAL & COMPLEMENTARY MEDICINES Minimal information available on traditional medicines ADRs Drug interactions At risk groups e.g. alfalfa and exacerbation of SLE Misnomer of �because it is natural, it is safe Association of Black Cohosh with liver problems Health professionals should try to get as much information as possible Name of product Indication Place of purchase (esp for unregistered products)

21. PREGNANCY Very little information available on outcome data for drugs used in pregnancy Current issue of association between lamotrigine use and cleft palate syndrome ACE Inhibitors and congenital anomalies Should follow-up cases where drugs are prescribed intentionally or have been used inadvertently to monitor outcome of pregnancy, effect to the foetus/baby

22. ACTIVE INGREDIENTS WITHDRAWN THALIDOMIDE (1961) Congenital limb defects BENOXAPROFEN (1982) Hepatotoxicity PHENFORMIN (1982) Lactic acidosis FENFLURAMINE (1997) Heart-valve abnormalities ASTEMIZOLE Many drug interactions PHENYLPROPANOLAMINE(2000) Haemorragic stroke KAVA KAVA Liver abnormalities CERIVASTATIN Rhabdomyolysis CISAPRIDE Cardiac arrythmias ROFECOXIB (2004) Cardiovascular events VALDECOXIB (2005) Cardiovascular events, serious skin reactions COMFREY, SENECIO Nephrotoxicity TEGASEROD (2007) Cardiovascular events CLOBUTINOL (2007) Cardiac arrhythmia

23. COMMUNICATING THE OUTCOME OF PV DHCP Letter � product holders Product Alerts � National Health Authorities Media statements - National Health Authorities/Pharmacovigilance Centres Newsletters � National Pharmacovigilance Centres and WHO Feedback to reporters � National Pharmacovigilance Centres

24. INTERNATIONAL COOPERTATION

25. WHO PROGRAMME FOR INTERNATIONAL DRUG MONITORING Started 1968 Located in Uppsala, Sweden Collaborating centre for maintaining global ADR database - Vigibase

26. Roles of WHO Collaborating Centre Identify early warning signals of serious adverse reactions to medicines Evaluate the hazard Undertake research into the mechanisms of action to aid the development of safer and more effective medicines

31. SO�.WHAT IS OUR ROLE? SEND NOT ONLY QUANTITY BUT�. QUALITY REPORTS

32. HOW? Monitor clinical status of patients Identify the correct ADRs not side effects Get more information Investigate at hospital level Help doctors to fill-up the forms Keep patient�s record if more information needed

33. TERIMA KASIH