Chapter 6 PHARMACOVIGELANCE. M.G.Rajanandh, Department of Pharmacy Practice, SRM College of Pharmacy, SRM University.

Transcription

1 Chapter 6 PHARMACOVIGELANCE M.G.Rajanandh, Department of Pharmacy Practice, SRM College of Pharmacy, SRM University.

2 DEFENITION: Pharmacovigilance (abbreviated PV or PhV) is the Pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term side effects of medicines.

3 WHO DEFENITION FOR ADR: According to WHO an ADR is defined as an nauxious,uintended response to drugs which occur at doses normally used in man for prophylaxis diagnosis or therapy of disease or altered physiological function.

4 FDA DEFENITION: FDA defines ADR as any undesired experience associated with the use of drugs whether or not considered as drug releated and includes any side effect, injury, toxicity or sensitive reaction or significant failure of expected pharmacological action.

5 PREDISPOSING FACTORS: 1. RACE: certain population in africa and south east asia have people who are defecient in glucose 6 phosphate dehydrogenase, such individuals are at substancial risk of developing hemolytic crises after the useof anti malarial drugs like primaquine. The rate at which drugs are acetyated varies considerably between ethinic groups. Rapid acetylators predominate among eskimos and slow acetylators among jews. Slow acetylators are likely to suffer from peripheral neuropathy due to INH.

6 2.GENDER: Women are likely to suffer from certain ADR than men. Agranulocytosis caused by phenylbutazone or chloramphenicol is 3 times more potent in women than in men. 3. AGE: The elderly over the age of 60 years are more suceptible for ADR than the younger groups. It is well known that elderly are more sensitive to analgesics and become more confused with barbiturates. After a standard IV dose of pethidine, the plasma concentration is higher and half life is longer in older than in younger patients.

7 In younger patients, neonates when premature, some enzymes involved in drug metabolism and elimination are poorly developed and consequently the risk of ADR is high. 4. ALLERGIC DISORDER: HAZARDOUS DRUGS: Chloramphenicol Sulphonamides barbiturates Patients with allergic disorder and hyper sensitivity reaction are more likely to develope from ADR.

8 5. RENAL AND HEPATIC DISEASES: Impaired renal and hepatic function predisposes ADR to those drugs that are wholly or mainly excreted unchanged in urine. 6.PLASMA PRITEIN BINDING: The pharmacological action and toxicity of certain drugs are influenced by degree to which they bind to plasma protein, mainly to albumin. A decrease in plasma albumin level due to age, malnutrition or disease and metabolism of drugs that are highly protein bound. Example: WARFARIN.

9 7. FORMULATION OF THE DRUG: Epidemics of particular drug ADR occured because of toxic vehicles or change in formulation when pharmaceutical manufacturer change the execipients present in some capsules of phenytoin in the form of calcium sulphate dihydrate to lactose, many patients develop symptoms of phenytoin toxicity.

10 PATHOGENESIS OF ADR: ADR are classified as those occuring due to Over dose Intolerance Side effects Secondary effects Idiosyncrasy Hyper sensitivity.

11 PHARMACOLOGICALLY: TYPE A ( AUGMENTED ADR) TYPE B (BIZZARRE ADR)

12 TYPE A: ( AUGMENTED ADR) These ADR are result of an exaggeration but other wise normal pharmacological action of a drug given in usual therapeutic doses. TYPE A is largely predictable on basis of a drug s known pharmacology. They are mostly dose dependent, their morbidity is high, but mortality is generally low.

13 TYPE B: ( BIZARRE ADR) These reactions are aberrant effects that are not to be expected from pharmacological action of drug given in normal way. Malignant hyper thermia, acute porphyria and immunological reaction fall under thus category. Usually un predictable but if it occurs mortality is high.

14 MANIFESTATIONS OF ADR: Dermatological manifestation. Gastrointestinal manifestation Hepatotoxicity Nephrotoxicity Haematological Ototoxicity Ocular toxicity Neuro toxicity Pulmonary disease Endocrine disorder Carcinogenecity Teratogenecity Hypersensitivity Drug allergy.

15 DETECTION OF ADR: Drug oriented system based on COHORT STUDIES. Disease oriented system called CASE CONTROL STUDIES. Complication oriented system.

16 ADR REPOTING FORM:

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18 ADR is first reported to the manufacturer and FDA. Then it is published in articles and presentations are given to the medical community.

19 Wider scope of pharmacovigilance Adverse reactions Type A Type B Lack of effect counterfeiting resistance interaction Quality problems Dependence and abuse Poisoning Medication errors

20 PHARMACOVIGILANCE WHO DEFINITION The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problem

21 Expansion of WHO Drug Monitoring Programme Database enriched not only problems seen in industrialized countries Drugs against tropical diseases Better monitoring of traditional medicines Another kind of co morbidity Effects of malnutrition

22 International Differences (Quantitative and Qualitative) disease prevalence genetic social cultural healthcare systems health professional practices indication for, and use of medicines pharmaceutical formulations drug monitoring practices Each country needs it s own pharmacovigilance system

23 3. More partners in pharmacovigilance Physicians Dentists Pharmacists Nurses Traditional healers Other health workers Patients Manufacturers

24 Where to report? Hospital DTC Regional Centre Patient Health Professional National Centre Manufacturer

25 Where to report? Hospital DTC Regional Centre Patient Health Professional National Centre Manufacturer

26 Pilot schemes for patient reporting Australia Canada Denmark (France HIV/AIDS) The Netherlands Sweden United Kingdom USA

27 4. More regulations International Conference on Harmonization (ICH) Established in 1991 to harmonize regulatory requirements for new chemical entities Regulators and industry from Europe, Japan, United States Observers from Canada, EFTA and WHO Legal implementation the aim

28 Topics relevant to pharmacovigilance E2, Clinical Safety E2A, Definitions and Standards for Expedited Reporting E2B, Data Elements for Transmission of ADR reports E2C, Periodic Safety Update Reports E2E, Pharmacovigilance planning

29 Topics relevant to pharmacovigilance M1, Medical Terminology (MedDRA) M2, Electronic Standards for the Transfer of Regulatory Information and Data (ESTRI) M5, Data Elements and Standards for Drug Dictionaries

30 Developments in ICH Countries Strong focus on regulatory requirements/actions Serious, unlabelled reactions to new drugs Pharmacovigilance planning and risk management Major problems in health care neglected Industry stewardship has major role Standardized format for exchange of case information E2b and MedDRA

31 Concept of E2E Guideline Clinical Trials Available Data/information NDA Review Approval Product Launch On the Market Pharmacovigilance Specification Pharmacovigilance Activities Pharmacovigilance Plan

32 E2E Pharmacovigilance planning Pharmacovigilance Specification is a summary of the: Important identified risks, Important potential risks, and Important missing information about a product.

33 E2E Pharmacovigilance planning Pharmacovigilance Plan is a structure for documenting the proposed pharmacovigilance methods to address the issues identified in the Pharmacovigilance Specification.

34 5. New opportunities Public Health Programmes Characteristics Vertical and intensive programmes Prophylaxis : vaccination, preventive treatment (ivermectine, albendazole, antibiotic and antiparasitic prophylaxis ) Treatment (artemisinine derivatives against malaria, ARVs, Tuberculosis, Schistosomiasis...) Eradication (lymphatic filariasis, Trachomatis, Leprosis, poliomyelitis elimination programmes ) Involve distribution of massive amounts of drugs and vaccines

35 Public Health Programmes Need to monitor: ADRs from drugs Misuse Dependence Effect on pregnancy and children Therapeutic failures (resistance, quality defects, counterfeits)

36 6. New methods Statistical methods to identify disproportionality in reporting (data mining) Relevant for big databases Objective screening tool Strong statistical associations highlighted for clinical assessment Complementary to other methods