Pharmacovigilance and ADRs

Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines.

1. PHARMACOVIGILENCE PRESENTED BY: Dr. S P SRINIVAS NAYAK, Assistant Professor, SUCP, Hyderabad.

2. Lets start with a case. A 25 year old woman was admitted to a medicine ward with the complaints of 4-5 episodes of vomiting and epigastric discomfort. she had been diagnosed with type 2 diabetes and was receiving glimepride 1 mg with metformin 500 mg once daily. her blood glucose level was under control. on admission she was prescribed with oral pantoprazole 40 mg once daily and IV ondansetron 4mg thrice daily. She continued OHD, WITHIN A FEW MINUTES OF RECEIVING ONDONSETRON, the pt developed utricaria and redness all over the body . She didn’t complain of pruritis . She was treated with inj. Dexamethasone 4mg and oral cetrezene 10mg . The reaction abated within few minutes. sultan-ul-uloom college of pharmacy

3. Concepts and learning objectives. What is ADR/ADE their classifications. Mechanisms of ADRs Identification of predisposing factors of ADRs Establish causality relationship How to report ADRs Prevention of ADRs Role of pharmacist in decting , Assessing and managing ADRs sultan-ul-uloom college of pharmacy

4. Definitions Adverse Event (AE): 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 . Adverse Drug Reaction (ADR): Any response to a drug which is noxious and unintended occurs at doses normally used in man for prophylaxix , trreatment , diagnosis or modyfying physiologic function it requires treatment or decrease in dose or indicates caution in future use of the same drug . Therefore, an adverse drug reaction is an adverse event with a causal link to a drug sultan-ul-uloom college of pharmacy

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8. What is Pharmacovigilance ? Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines. sultan-ul-uloom college of pharmacy

9. What is the minimum criterion required for a valid case according to WHO? a . An identifiable reporter b . An identifiable patient c . A suspect product d . An adverse drug event sultan-ul-uloom college of pharmacy

10. Classification of ADRs Depending on Onset of event : Acute (<60 minutes), Sub-acute (1-24 hrs ) and Latent (>2 days) Type of reaction: Type A (Augmented), B (Bizarre), C (Chemical ), D (Delayed), E (Exit), F (Familial), G ( Genotoxicity ), H (Hypersensitivity), U (Un classified) Severity : Minor, Moderate, Severe, Lethal ADRs Others : Side effects, Secondary effects, Toxic effects, Intolerance, Idiosyncrasy, Drug allergy, Photosensitivity, Drug Dependence, Drug Withdrawal Reactions, Teratogenicity, Mutagenicity, Carcinogenicity, Drug induced disease (Iatrogenic) sultan-ul-uloom college of pharmacy

11. Type A (Augmented) reactions Type A (Augmented) reactions are those which can be predicted from the known pharmacology of the drug Dose dependent , Can be alleviated by a dose reduction Examples: Anticoagulants - Bleeding, Beta blockers - Bradycardia , Nitrates - Headache , Prazosin - Postural hypotension . Benzodiazepines - Sedation Furosemide - Water and electrolyte imbalance Heparin , warfarin - Spontaneous bleeding Insulin - Hypoglycemia sultan-ul-uloom college of pharmacy

12. More examples of type A ADRs INH, Rifampicin, PZA – Hepatotoxicity Streptomycin - Ototoxicity, nephrotoxicity Captopril – Cough Simvastatin – Rhabdomyolysis Nitrates – Headache Propranolol – Bronchial asthma Tetracycline – Hypoplasia of the teeth sultan-ul-uloom college of pharmacy

13. Type B (Bizarre) reactions Type B (Bizarre) reactions are those Cannot be predicted from the pharmacology of the drug They are Not dose dependent, Host dependent factors important in predisposition E.g. Penicillin causes Anaphylaxis , Anticonvulsant induced Hypersensitivity Stevens-Johnson’s Syndrome by mostly antibiotics Hemolytic anemia induced by Cephalosporins, Dapsone , Levodopa, Levofloxacin, Methyldopa, Nitrofurantoin sultan-ul-uloom college of pharmacy

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16. TYPE C REACTIONS/CONTINUOUS/ CHEMICAL REACTIONS The Biological characteristics can be predicted from the chemical structure of the drug/metabolite E.g . Paracetamol - Hepatotoxicity l ong term effects are usually related to the dose and duration of treatment. Examples: Ethambutol – Retinopathy. NSAIDs - Nephrotoxicity sultan-ul-uloom college of pharmacy

17. Type D (Delayed) reactions Occur after many years of treatment. Can be due to accumulation. E.g. Chemotherapy - Secondary tumours Phenytoin during pregnancy - Teratogenic effects Antipsychotics - Tardive dyskinesia Thalidomide - Phocomelia sultan-ul-uloom college of pharmacy

18. TYPE E REACTIONS OR ENDING OF USE These are usually the Withdrawal Syndromes Examples : Benzodiazepines – Rebound insomnia, agitation Clonidine – Rebound hypertension Corticosteroids – Acute adrenal insufficiency. sultan-ul-uloom college of pharmacy

19. TYPE F REACTIONS OR FAILURE OF EFFICACY Main causes for type f reactions are medication errors: Counterfeit medicines Underdosing of medications Drug interactions Examples: 1. Warfarin which is highly protein bound is displaced by valproic acid leading to bleeding. 2. Aspirin inhibit platelet aggregation together with heparin an anticoagulant leads increased risk of bleeding . 3. SU with Sulfonamides. sultan-ul-uloom college of pharmacy

20. OTHER EXAMPLES Secondary Effects- a) Corticosteroids → ↓Immunity → Latent T.B. activated b) Tetracyclines → ↓Bacterial flora → Super-infection. 3 . Toxic Effects-Exaggerated form of side effects due to overdosage /prolonged use like a)High dose heparin → Bleeding b)Prolonged use of streptomycin → Ototoxicity, nephrotoxicity sultan-ul-uloom college of pharmacy

21. Factors causing ADRs Many factors can increase the likelihood of an adverse drug reaction (any unwanted effects of a drug). They include: Hereditary factors Certain diseases Simultaneous use of several drugs Very young or old age Pregnancy Breastfeeding sultan-ul-uloom college of pharmacy

22. What is Pharmacovigilance ? Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines. sultan-ul-uloom college of pharmacy

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24. POST MARKETING SURVEILLANCE : Postmarketing surveillance  (PMS), also known as  post market surveillance , is the practice of monitoring the safety of a pharmaceutical drug or medical device  after  it has been released on the  market  and is an important part of the science of pharmacovigilance sultan-ul-uloom college of pharmacy

25. ADR REPORTING It is reporting of undocumented ADRs. Benefits of ADR Reporting: Assess the safety of drug therapies, especially recently approved drugs . Provides updated drug safety information to health care professionals and other stakeholders Measuring the economic impact of ADR prevention as manifested through reduced hospitalization, optimal and economical drug use, and minimized organizational liability Indian Pharmacopoeia Commission, Pharmacovigilance Programme of India sultan-ul-uloom college of pharmacy

26. Types of ADR reporting EXPEDITED REPORTING This refers to ICSRs (individual case safety reports) that involve a serious and unlisted event (an event not described in the drug's labeling) that is considered related to the use of the drug (US FDA). sultan-ul-uloom college of pharmacy

27. CLINICAL TRIAL REPORTING Also known as AE (adverse event) or SAE (serious AE) reporting from clinical trials , safety information from clinical studies is used to establish a drug's safety profile in humans and is a key component that drug regulatory authorities consider in the decision-making as to whether to grant or deny market authorization (market approval) for a drug. sultan-ul-uloom college of pharmacy

28. SPONTANEOUS REPORTING Spontaneous reports are termed spontaneous as they take place during the clinician's normal diagnostic appraisal of a patient, when the clinician is drawing the conclusion that the drug may be implicated in the causality of the event. Spontaneous reporting system relies on vigilant physicians and other healthcare professionals who not only generate a suspicion of an ADR, but also report it. It is an important source of regulatory actions such as taking a drug off the market or a label change due to safety problems. sultan-ul-uloom college of pharmacy

29. AGGREGATE REPORTING Aggregate reporting, also known as periodic reporting, plays a key role in the safety assessment of drugs. Aggregate reporting involves the compilation of safety data for a drug over a prolonged period of time (months or years), as opposed to single-case reporting which, by definition, involves only individual AE reports . This is a document that is submitted to drug regulatory agencies in Europe, the US and Japan (ICH countries), as well as other countries around the world. sultan-ul-uloom college of pharmacy

30. SPONTANIOUS ADR REPORTING FORM sultan-ul-uloom college of pharmacy

31. Causality Assessment Causality refers to the relationship of a given adverse event to a specific drug. Causality determination (or assessment) is often difficult because of the lack of clear-cut or reliable data. While one may assume that a positive temporal relationship might "prove" a positive causal relationship, this is not always the case . METHODS: Opinions of experts, clinical judgements Algorithms or assessment methods Probabilistic and bayesian approaches sultan-ul-uloom college of pharmacy

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33. WHO–UMC CAUSALITY scale CAUSALITY TERM ASSESSMENT CRITERIA (ALL POINTS SHOULD BE REASONABLY COMPLIED) 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) Event definitive pharmacologically or phenomenologically (ie, an objective and specific medical disorder or a recognized pharmacologic phenomenon) 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 clinically reasonable Rechallenge not required sultan-ul-uloom college of pharmacy

34. Possible Event or laboratory test abnormality, with 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 time to drug intake that makes a relationship improbable (but not impossible) Disease or other drugs provide plausible explanation Conditional/unclassified Event or laboratory test abnormality More data for proper assessment needed, or Additional data under examination Unassessable /unclassifiable Report suggesting an adverse reaction Cannot be judged because information is insufficient or contradictory Data cannot be supplemented or verified sultan-ul-uloom college of pharmacy

35. ROLE OF PHARMACIST IN ADR monitoring Clinical pharmacists have a crucial role in reporting a larger number of ADRs which leads to fast management and in turn resulted in reduced number of morbidity and mortality cases. Moreover , clinical pharmacists could discuss the prescribed medication with the physician to change it if it isn’t suitable for the patient, thereby improving the patients’ outcome. sultan-ul-uloom college of pharmacy

36. A pharmacist plays a pivotal role in the identification, detection, prevention, and management of drug-drug interactions, drug-food interactions and adrs . Pharmacist can carry out such activities in inpatient setting, while taking part in viewing charts during ward rounds, and during medication management while dealing with prescriptions. Since pharmacists have a vast knowledge on drugs and therapeutics, their ability to discover and deal with adrs is quite important. Keeping in view the reporting of adrs , a pharmacist’s participation enhances reporting rate with higher calibre . sultan-ul-uloom college of pharmacy

37. The intervention of pharmacists by organising lectures and group discussions thus providing information about the importance, seriousness, preventability and necessity of reporting shows heightened improvement of knowledge, attitude and perception about adrs . All health professionals play their respective roles in balancing between benefits and risks of medication when it is introduced in the market. However , the expertise of a pharmacist about a drug, especially if newly marketed, play a more important role in adrs reporting to the authorities which helps in either withdrawing the product from the market or cause labelling changes. Pharmacists working in community pharmacy have an added advantage of detecting and reporting adrs while dealing with on the counter prescriptions and herbal products. In a community pharmacy, a pharmacist may not have direct and definite patient list but the patients coming to the same pharmacy to refill their prescription gives the pharmacist an opportunity to detect a possible adr that the patient might be experiencing and can help in the management and the reporting of the said adr . sultan-ul-uloom college of pharmacy

38. Thank you --- Dr. S P Srinivas Nayak , Sultan- ul - Uloom college of Pharmacy, Hyderabad, Telangana , India . Email: [email protected] sultan-ul-uloom college of pharmacy