Adverse drug reaction monitoring and reporting

ADR, types, reprting and monitoring

1. ADVERSE DRUG REACTION MONITORING AND REPORTING THUSHARA C 1 ST YEAR MPHARM GRACE COLLEGE OF PHARMACY

2. Any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function DEFINITION

3. Classification of ADRs Type A (Augmented) Type B (Bizarre) Type C (Chemical) Type D (Delayed) Type E (Exit/End of treatment) Type F (Familial) Type G (Genotoxicity) Type H (Hypersensitivity) Type U (Un classified)

4. Reactions which can be predicted from the known pharmacology of the drug Dose dependent, Can be alleviated by a dose reduction E.g. Anticoagulants  Bleeding, Beta blockers  B radycardia, Nitrates  H eadache, Prazosin  P ostural hypotension. Type A (Augmented) reactions Type A (augmented)

5. Cannot be predicted from the pharmacology of the drug Not dose dependent, Host dependent factors important in predisposition E.g . Penicillin  A naphylaxis, Anticonvulsant  H ypersensitivity Type B (BIZZARE) REACTIONS

6. Biological characteristics can be predicted from the chemical structure of the drug/metabolite E.g. Paracetamol  H epatotoxicity Type C (Chemical) reactions TYPE C (CHEMICAL REACTIONS

7. 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 Analgesics  Nephropathy TYPE D (DELAYED) REACTIONS

8. Type E (End of treatment) reactions Occur on withdrawal especially when drug is stopped abruptly E.g . Phenytoin withdrawal  S eizures, Steroid withdrawal  Adrenocortical insufficiency. TYPE D (END OF TREATMENT ) REACTIONS

9. PREDISPOSING FACTORS POLY PHARMACY : Patients on multiple drug therapy are more prone to develop an ADR Alteration of drug effect through interaction mechanism or by synergism Risk increases with increase in the no: of drugs administered

10. Increased risk due to multiple drugs use for their diseses Impaired hepatic and renal status are also at high risk of developing an ADR Patient with decreased renal function treated with aminoglycosides increased risk of nephrotoxicity MULTIPLE AND INTERCURRENT DISEASES

11. AGE Elderly and pediatric patients are more vulnerable to ADRs In elderly patients physiological changes Eg : nitrate or ACE inhibitor induce postural hypotension In neonates drug handling capacity differ compared to adults Eg : grey baby syndrome with chloramphenicol

12. DRUG CHARACTERISTICS : Some drugs are highly toxic in nature Eg : cytotoxic drugs result in nausea and vomiting Narrow therapeutic range drugs like digoxin and gentamicin slight increase in concentration may result in toxicity

13. GENDER Womens are more susceptible to ADRs than females, reasons are physiological, pharmacokinetic, pharmacodynamic and hormonal. Eg : chloramphenicol induced aplastic anaemia and phenylbutazone induced agranulocytosis are twice and thrice as common in women as in man,respectivley

14. RACE AND GENETIC FACTORS ADRs are more common in genetically predispose individuals Eg : G6PD deficient patient high risk of devoleping heamolysis due to primaquine

15. DETECTION OF ADRs pre- marketing studies Post –marketing surveillance Under reporting Communicating ADRs

16. Identifying adverse drug reaction (ADR). Assessing causality between drug and suspected reaction by using various algorithms. Documentation of ADR in patient’s medical records. Reporting serious ADRs to pharmacovigilance centers /ADR regulating authorities STEPS INVOLVE ADR MONITORING

17. During the development of new medicines, their safety is tested in animal models. Specific animal studies for carcinogenicity, teratogenicity and mutagenicity are also available Clinical trials are carried out in 3 different phases prior to the submission of a marketing authorization application Clinical trials normally identifies ADRs of frequency greater that .5-1.0% PREMARKETING STUDIES

18. Pharmavigilance methodologies are used for detection of risk and for the collection of risk information Powerful and cost effective system for the identification of unknown drug-related risk is spontaneous adverse drug reactions reporting Health care practitioner should see it as a part of professional duty report ADR result in a patient under his care Concerned identifying product defect, intoxicants and abuse and unexpected lack of therapeutic effect POST MARKETING SURVEILLANCE

19. Two epidemiological methods are most commonly used are Cohort studies Control studies Cohort studies : Patient exposed to a particular drug are followed up actively and systematically and ADR frequencies are compared to an unexposed control population

20. control studies : Individuals affected by the adverse event being studied are identified . Each case is matched with several disease – free control patients randomly recruited from the study base. Both cases and controls are investigated their exposure to possible causative agents prior to occurrence of the event. The odd ratio calculated on the basis of exposure data

21. The health care professionals should be very vigilant in detecting ADRs. ADR may be detected during ward rounds with medical team ADRs detected during review of patient chart , patient counseling, medication history review, communicating with other health professionals ROLE OF HEALTHCARE PROFESSIONALS

22. To assist ADR health care professionals should closely monitor patients who are at high risk include Patients with renal or hepatic impairment Patients taking drugs which have potential to cause ADR . Eg : DIGITOXIN Patient who have had previous allergic reactions Patient taking multiple drugs Pregnant and breast feeding women

23. First step in the detection of ADRs is collection of data. Data collected includes , patients demographic information Presenting complaints Past medication history Drug therapy details including over the counter, current medications , medication on admission Lab data such as hematological, liver and renal function test.

24. The information can be obtained from the following sources Patient’s case note and treatment chart Patient interview Laboratory data sources Communication with healthcare professionals

25. Under reporting Under reporting varies with no: of factors Reporting higher for new drugs than for old Serious reactions are reported to a higher degree Type B reactions are reported more commonly than their share of events in practice Reporting is affected by promotional claims of the drug sponsor. Reporting is affected by general publicity around the ADR reporting scheme.

26. The reasons more often by health professionals for not reporting are : Lack of time Lack of knowledge on what, how or where to report The drug-reaction association is uncertain The reaction is already well known Guilt or fear of litigation Belief that all registered medicines are safe Non-availability of reporting forms

27. Activities that may increase the reporting rate include Ease of reporting, improve the design of reporting form, using online reporting Providing feedback to clinicians in the form of articles in journals, ADR bulletins, news letters Participate in pre and post graduate education programmes Collaboration with local Drug and Therapeutics committees Integrating pharmacovigilance in public healthcare programmes

28. Knowledge about rational and safe use of medicines needs to be provided, During basic training of health professionals Through continuous education programmes to health professionals. By specially designated drug information centers. Through packaged inserts and patient counseling COMMUNICATING ADRs

29. REFERENCE Text book of clinical pharmacy practice – G Parthasarathy . Page no: 105-118