22-01-23 Pharmacovigilance Workshop ppt edited.pptx

This ppt contains detailed information of pharmacovogilance

1. Pharmacovigilance DR. VEENA RANI VEMURI Associate Professor Department of Pharmacology

2. LEARNING OBJECTIVES - ADR

3. Content of the Session 3

4. What is Pharmacovigilance ? 4

5. 5 The central drugs standard control organization (CDSCO), New Delhi, under the aegis of the Ministry of health & family welfare, the government of India has initiated a nationwide pharmacovigilance Program ( P vPi ) and Indian Pharmacopoeia C ommission (IPC), G haziabad, (U.P.) Is a national co-ordinating center for the program. The pharmacovigilance program of India ( P vPi ) , mission is to safeguard the health of the Indian population by ensuring that the benefit of the use of medicine outweighs the risks associated with its use. Pvpi has succeeded in establishing 395 adverse drug reaction monitoring centers (AMC) across the country. Currently, pvpi ranks 9th in reporting of ICSRs to WHO-UMC.

6. Why PHARMACOVIGILANCE Pharmaceutical companies are required by law in all countries to report ADRs during clinical trials, testing new drugs on people before they are made generally available. Because these pre-registration clinical trials involve only several thousand patients at most, less common ADRs are often unknown when a drug enters the market.

7. Thalidomide disaster Rofecoxib Withdrawal Benfluorex (Mediator) withdrawal Lots of drugs entering the market, the tendency to self-medicate, herbal medicines, OTC medicines. There is also the issue of off-label use, a drug used in unapproved indications which needs to be addressed from a safety perspective. 7 Why PHARMACOVIGILANCE

8. Objectives of Pharmacovigilance Detection of Risk Factors Early Identification of Unknown Safety Problems Quantifying the Probability of Risk Measurement of Effectiveness

9. Importance of Pharmacovigilance To improve the patient's safety. Providing reliable information for the efficient assessment of the risk-benefit profile of medicines. Encouraging the safe, rational, and more effective (including cost-effective) use of various medicines. Promote education, understanding, and clinical training in pharmacovigilance and its effective availability to the public.

10. Definitions of AE/SAE/SUSAR : 1/3 10

11. Definitions of AE/SAE/SUSAR : 2/3 11

12. Definitions of AE/SAE/SUSAR : 3/3 12 7. Suspected Unexpected Serious Adverse Reaction (SUSAR): it is defined as below: Suspected: Causality is assessed as Reasonable possibility that the event is due to the study drug. Unexpected: An unexpected adverse event that is not identified in nature, severity, or frequency in the current Investigator’s Brochure/USPI/Package insert/SmPC. 6. A Serious Adverse Event (SAE) : It is defined as an untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in-subject hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; and/or Other medically Important condition /Medically Significant Seriousness is a criteria defined by legislation and severity is stated by the reporting physician in order to state the intensity of the adverse event. Hence a treating physician/investigator’s assessment is mandatory.

13. Reporting tools Available Suspected ADR reporting FORM (version 1.4) AEFI – Adverse event following immunization case notification FORM TRRF - Transfusion reaction reporting FORM Medical device Adverse event reporting FORM Medicine side effects reporting FORM (for consumers)

14. 1. Suspected ADR reporting FORM (version 1.4) ADR_Reporting_Form_1.4_Version.pdf (ipc.gov.in)

15. 2. AEFI – Adverse event following immunization https://ipc.gov.in/images/pdf/File650.pdf

16. 3. TRRF - Transfusion reaction reporting form https://nib.gov.in/Haemovigilance/TRRF_Form_new.pdf

17. 3. TRRF - Transfusion reaction reporting form https://nib.gov.in/Haemovigilance/TRRF_Form_new.pdf

18. 4. Medical device and Materiovigilance programme https://ipc.gov.in/images/MEDICAL_DEVICE_ADVERSE_EVENT_REPORTING_FORM_editable.pdf

19. 4. Medical device and Materiovigilance programme https://ipc.gov.in/images/MEDICAL_DEVICE_ADVERSE_EVENT_REPORTING_FORM_editable.pdf

20. 5. Medicine side effects reporting form for consumers https://ipc.gov.in/images/pdf/File492.pdf

21. Why should HCPs report adverse event? All HCPs can report adverse events ( including pharmacists , nurses, lab. technicians , doctors , students ) even patients and consumers can report too . There is no legal obligation or action for reporting , nor there is any fee to be paid or earned . Reporting an adverse event will help bring safer and more effective drugs for patients. HCPs will have more information about drugs , indications, contraindications , warnings, precautions, and how to anticipate and treat if an adverse event occurs in the patient. 21

22. What happens to reported AE data? Patients/Consumer/HCP Pharma companies / Medical college / Health authority ( PvPI ) Health Authorities/WHO-UMC Investigator /HCP/ Pharmacist Data Management Medical review Patient/ Consumers Communication for safe use of drug via Package insert USPI/SmPC Dear HCP letter Trainings/CME Social Media messages Actions Pharmacovigilance Team A dverse events occurs Safety report forms 22

23. What happens to reported AE data? Package insert Risk minimization measure Patient leaflets HCP Training and leaflets More studies Collection and monitoring

24. Vaccine PV

25. What and When AE information should be reported by HCP? For regulatory reporting, the minimum data elements for a initial notification of an SAE are: An identifiable reporter An identifiable patient An adverse reaction A suspect drug (Investigational product as per clinical study protocol/marketed product or products) Complete AE form data as much is available on the form As soon as possible but within 15 days after you become aware of the adverse event (non-fatal and non-life-threatening) As soon as possible but within 7 days after you become aware of the adverse event (for a fatal or life-threatening) As soon as possible 25

26. FUNCTIONS OF A PVPI ADR MONITORING CENTRE IN A MEDICAL COLLEGE 1. Collection of ADR reports 2. Follow up to check completeness of SOP 3. Data entry into VigiFlow 4. Reporting to PvPI NCC through VigiFlow 5. Training/sensitization/feedback through newsletters circulated by PvPI NCC.

27. Causality Assessment To determine the 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 the nature and frequency of adverse reactions)‏ Medical or pharmacological plausibility (signs and symptoms, tests, pathological findings, mechanism)‏ Likelihood or exclusion of other causes

28. Need to look at - Product indication; duration of medication use • Temporal relationship of ADR – Appearance of ADR = “challenge” – Disappearance of ADR = positive “ dechallenge ” – Reappearance of ADR = positive “rechallenge” • Previous exposure = “pre-challenge” (previous exposure to the suspect drug) – Positive pre-challenge = ADR occurred in the past when the patient exposed to drug – Negative pre-challenge = ADR did not occur in the past when the patient exposed to drug

29. WHO-UMC CAUSALITY CATEGORIES Certain - Event or laboratory test abnormality, with plausible time relationship to drug intake Cannot be explained by disease or other drugs. Response to withdrawal plausible (pharmacologically, pathologically) Rechallenge satisfactory, if necessary. Probable/Likely - - Event or laboratory test abnormality, with reasonable time relationship to drug intake Unlikely to be attributed to disease or other drugs. Response to withdrawal is clinically reasonable. Rechallenge not required Possible – Event or laboratory test abnormality, with a reasonable time relationship to drug intake. Could also be explained by disease or other drugs. Information on drug withdrawal may be lacking or unclear Unlikely - Event or laboratory test abnormality, with a reasonable time relationship to drug intake that makes the relationship improbable but not impossible . Disease or other drugs provide a plausible explanation Conditional/Unclassified - More data for proper assessment needed, or Additional data under examination Unassessible /Unclassifiable - Report suggesting an adverse reaction Cannot be judged because information is insufficient or contradictory. Data cannot be supplemented or verified

30. 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

31. What to Report Any drug suspecting of causing – Death Life-threatening event Hospitalization Disability Congenital Anomaly Requiring intervention to prevent permanent impairment or damage

32. Special Cases for Pharmacovigilance Some groups of medicinal products are not required to document their safety – natural medicines, homeopathic preparations Natural (herbal) medicines Exact composition is often not known, efficacy nor safety is usually not documented Marketing Authorization is granted on base of “traditional use”

33. LAW Will reporting have any negative consequences on the health care professionals or the patient?

34. LAW (contd.)

35. A. Patient Information 1 Patient Initials - 2 Age at the time of Event or Date of Birth 3 Sex Male Female Other 4 Weight (kg)

36. B. Suspected Adverse Reaction 5 Date of Reaction started (dd/mm/yyyy) 6 Date of recovery (dd/mm/yyyy) 7 Describe reaction or problem

37. C. Suspected Medication 8 Name (Brand and/or Generic) Manufacturer (if known) Batch No. /Lot No. Exp. Date (if known) Dose used Route used Frequency (OD, BD, etc) Therapy dates Date Started Date Stopped Indication Causality Assessment

38. C. Suspected Medication 9 Action Taken (Please tick) Drug Withd r a wn Dose increased Dose reduc e d Dose not changed Not a p p li c a ble Unknown i ii iii iv

39. C. Suspected Medication 10 Reaction reappeared after reintroduction (please tick) Yes No Effect unknown Dose (if re i nt r oduce d ) i ii iii iv

40. C. Suspected Medication 11 Concomitant medical products Including self-medication and herbal remedies with therapy dates (Exclude those used to treat reaction) Name (Brand/ Generic) Dose used Route Used Fre qu ency (OD, BD, etc.) Therapy dates Indication Date Started Date Stopped i ii iii iv

41. 12 Relevant tests/laboratory data with dates 13 Relevant medical / medication history (e.g. allergies, race, pregnancy, smoking, alcohol use, hepatic/renal dysfunction etc.)

42. 14 Seriousness of the reaction: No If Yes (Please tick anyone) Death (dd/mm/yyyy) Life threatening Hospitalization (initial or prolonged) Disability Congenital anomaly Required intervention to prevent permanent impairment / damage Other (specify)

43. 15 Outcomes Recovered Recovering Not recovered Fatal Recovered with sequelae Unknown

44. D. Reporter Details 16 Name and Professional Address Pin Email Tel. No. (with STD Code) Occupatio n S igna t ure 17 Date of this report (dd/mm/yyyy)

45. Mandatory Fields for Suspected ADR Reporting Form Patient initials Age at onset of reaction Date of onset of reaction Reaction term(s) Suspected medication Reporter information 1 2 5 7 8 16, 17

46. Case studies Keep your forms ready and fill in the details as shown

47. Case - 1 Manisha Singh, a 65-year-old female patient admitted to the hospital on 12.01.2023 with chief complaints of pain in the upper abdomen and nausea for the last 5 days. On physical examination, she had yellowish discoloration of the palm, conjunctiva, and nail bed. Her weight was 65 kg. She had a few episodes of psychotic attacks and was diagnosed with Schizophrenia, for which she was on Tab. Largactil (Chlorpromazine) 100 mg, 4 tablets at bedtime for the last 4 weeks. S he was also taking Tab. Diclofenac 50 mg twice-a-day (self-medication) for abdominal pain for three days before hospital admission . She was investigated on the day of admission. Laboratory parameters are as follows : Alkaline Phosphatase = 180 U/L (Normal range: 25 – 100 U/L) ALT = 205 U/L (Normal range: 10 – 40 Units/L) Total Bilirubin = 5.0 mg/dL (Normal range: 0.8 – 1.2 mg/dL) On admission, Chlorpromazine and Diclofenac therapy was stopped. Patient parameters showed improvement and pain subsided.

48. Causality Assessment – ADR Case 1 Categories Time se q uence Other drug disease ruled out Dechallenge Rechallenge Certain Yes Yes Yes Yes Probable Yes Yes Yes No Possible Yes No No No Unlikely No No No No

49. Case - 2 Mr . Sushant Gupta, a 30-year-old male with 68 kg weight was diagnosed as a case of bacterial meningitis. He was started empirically with Inj. Ceftriaxone 1 g IV BD and Inj. Vancomycin 500 mg IV QID on 10.08.2023. The first dose of Inj. Ceftriaxone was given at 8 am and Inj. Vancomycin was given at 9 am on 10.08.2023. After 10 minutes of the second drug administration, he started developing chills, rigors, fever, urticaria, and intense flushing. He was treated with Inj. Pheniramine 25 mg IM, following which the reaction completely subsided. Inj. Ceftriaxone was continued. However, the next doses of Inj. Vancomycin scheduled on day 1 was not given. On day 2, the Inj Vancomycin was re-introduced at 9 am to the patient. Similar symptoms developed again and quickly resolved after Inj. Pheniramine 25 mg IM. Inj Vancomycin Brand Name: Vanzid Manufacturer: SWACH Healthcare Batch number: KKIL098 Expiry date: Mar 2016 Inj Ceftriaxone Brand Name: Taximax Manufacturer: Wedley Labs Batch number: OPO659 Expiry date: Dec 2016

50. Causality Assessment – ADR Case 2 Categories Time se q uence Other drug disease ruled out Dechallenge Rechallenge Certain Yes Yes Yes Yes Probable Yes Yes Yes No Possible Yes No No No Unlikely No No No No

51. References K.D. Tripathi. Adverse Drug Effects . Essentials of Medical pharmacology 8th edition. New Delhi (India); Jaypee brothers publishers.2019. pg : 92-101. MvPI Toolkit - Indian Pharmacopoeia Commission (ipc.gov.in) https://nhsrcindia.org/hc-technology/materiovigilance-programme-of-india Haemovigilance Programme Of India ( HvPI ) (nib.gov.in) https://nib.gov.in/haemovigilance/HvPI_website/HvPI_index.html https://www.who-umc.org/global-pharmacovigilance/global-pharmacovigilance/50-years-of-pharmacovigilance/ https://link.springer.com/article/10.1007/s11096-018-0657-1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050268/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838749/ https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf https://www.who.int/teams/regulation-prequalification/regulation-and safety/pharmacovigilance/health-professionals-info/ aefi