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2 Why should I lose time to send a report of adverse drug reactions?

3 The voluntary ADR reporting was developed to detect rare, serious, unexpected adverse drug, mainly type B, reactions over 40 years ago.

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5 A response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function WHO, 1972 What is an adverse drug reaction?

6 Pharmacovigilance Monitoring and analysis of spontaneous adverse drug reactions WHO-CC: Uppsala Monitoring Centre, Sweden

7 WHO-CC Uppsala Monitoring Centre Collects volountary reports of Adveres Drug Reactions from all over the world

8 WHO Drug Monitoring Programme

9 WHO – WHO Collaborating Centre for International Drug Monitoring - The Uppsala Monitoring Centre > 4 million reports

10 SWEDIS Swedish Drug Information System ADR reports with causality assessment

11 Southern Region Lund and Malmö Northern Region Umeå Uppsala Region Uppsala Stockholm Region Stockholm Western Region Gothenburg South-east Region Linköping Six Health Care Regions - each with a medical school

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13 Causality Assessment Known reaction Time-relasionship Cannot be explained by the underlying diseases or medications

14 I stopped taking the medicine because I prefer the original disease to the side effects !

15 Causality Assessment Known reaction Time-relasionship Cannot be explained by the underlying diseases or medications Dissapperar at dechallenge Reappear at Rechallenge

16 ADR reports in Sweden

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19 Pharmacovigilance from a public health point of view

20 Bergman U, Wiholm B-E. Drug-related problems causing admission to a medical clinic. Eur J Clin Pharmacol 1981;20:

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23 Bergman U, Wiholm B-E. Drug-related problems causing admission to a medical clinic. Eur J Clin Pharmacol 1981;20: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

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25 Swedish ADR hospitalization studies 1. Beermann B, Biörck G, Groshinsky-Grind M. Läkemedelsbiverkningar och intoxikationer som orsak till intagning på invärtesmedicinsk klinik. Läkartidningen 1978;75: Bergman U, Wiholm B-E. Drug-related problems causing admission to a medical clinic. Eur J Clin Pharmacol 1981;20: Sarlöv C, Andersén-Karlsson E, von Bahr C. Läkemedelsbiverkningar leder till sjukhusvård för hjärtpatienter. Läkartidningen 2001;47: Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm B-E, Wahlin A et al. Adverse drug reaction as a cause for admissions to a department of internal medicine. Pharmacoepidemol Drug Safe 2002;11: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

26 ADR hospitalizations in % 1.Beermann B, Biörck G, Groshinsky-Grind M. Läkemedelsbiverkningar och intoxikationer som orsak till intagning på invärtesmedicinsk klinik. 9 % Läkartidningen 1978;75: Bergman U, Wiholm B-E. Drug-related problems causing admission 6 % to a medical clinic. Eur J Clin Pharmacol 1981;20: Sarlöv C, Andersén-Karlsson E, von Bahr C. Läkemedelsbiverkningar 14 % leder till sjukhusvård för hjärtpatienter. Läkartidningen 2001;47: Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm B-E, Wahlin A. Adverse drug reaction as a cause for admissions to a department of internal 12 % medicine. Pharmacoepidemol Drug Safe 2002;11: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records 11 % and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

27 Mean AGE in ADR hospitalizations 1.Beermann B, Biörck G, Groshinsky-Grind M. Läkemedelsbiverkningar och intoxikationer som orsak till intagning på invärtesmedicinsk klinik. 71 year Läkartidningen 1978;75: Bergman U, Wiholm B-E. Drug-related problems causing admission 66 year to a medical clinic. Eur J Clin Pharmacol 1981;20: Sarlöv C, Andersén-Karlsson E, von Bahr C. Läkemedelsbiverkningar 77 year leder till sjukhusvård för hjärtpatienter. Läkartidningen 2001;47: Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm B-E, Wahlin A. Adverse drug reaction as a cause for admissions to a department of internal 74 year medicine. Pharmacoepidemol Drug Safe 2002;11: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records 72 year and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

28 Number of drugs/patient with ADR hospitalizations 1.Beermann B, Biörck G, Groshinsky-Grind M. Läkemedelsbiverkningar och intoxikationer som orsak till intagning på invärtesmedicinsk klinik. 3,7 Läkartidningen 1978;75: Bergman U, Wiholm B-E. Drug-related problems causing admission 3,5 to a medical clinic. Eur J Clin Pharmacol 1981;20: Sarlöv C, Andersén-Karlsson E, von Bahr C. Läkemedelsbiverkningar 6,2 leder till sjukhusvård för hjärtpatienter. Läkartidningen 2001;47: Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm B-E, Wahlin A. Adverse drug reaction as a cause for admissions to a department of internal 7 medicine. Pharmacoepidemol Drug Safe 2002;11: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records 8,3 and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

29 % phararmacological (typ A) ADRs 1.Beermann B, Biörck G, Groshinsky-Grind M. Läkemedelsbiverkningar och intoxikationer som orsak till intagning på invärtesmedicinsk klinik. >75 % Läkartidningen 1978;75: Bergman U, Wiholm B-E. Drug-related problems causing admission >75 % to a medical clinic. Eur J Clin Pharmacol 1981;20: Sarlöv C, Andersén-Karlsson E, von Bahr C. Läkemedelsbiverkningar 100 % leder till sjukhusvård för hjärtpatienter. Läkartidningen 2001;47: Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm B-E, Wahlin A. Adverse drug reaction as a cause for admissions to a department of internal 91 % medicine. Pharmacoepidemol Drug Safe 2002;11: Von Euler M, Eliasson E, Öhlén G, Bergman U. Adverse drug reactions causing hospitalisation can be monitored from computerized medical records 89 % and thereby indicate the quality of drug utilisation. Pharmacoepidemiol Drug Safe 2006;15:

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31 In summary: ADRs in 2000 vs 1970s % more ADR hospitalizations More elderly patients More drugs per patient Pharmacologcal reactions (type A) dominats completely

32 Adverse drug reactions as cause of admission to hospital: prospective analysis of patients. British Medical Journal 2004;329;15-9 Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Kevin Park B and Breckenridge AM.

33 Types of ADRs –Type A Predictable from pharmacology of the drug, dose-dependent and preventable – 95%  Type B Bizzare, unpredictable from known pharmacology, and no dose-dependency — 5% Pirmohamed M. et al. Br Med J 329:15-19 (2004)

34 Types of ADRs –Type A Predictable from pharmacology of the drug, dose-dependent and preventable – 95%  Type B Bizzare, unpredictable from known pharmacology, and no dose-dependency — 5% ____________________________________ – 76% of patients were 65 years or over Pirmohamed M. et al. Br Med J 329:15-19 (2004)

35 How Many ADRs Were Avoidable? Definitely avoidable 8.6% Possibly avoidable 63.1% Not avoidable 28.1% 72 % of ADRs were definitely or possibly avoidable –Pirmohamed M. et al. Br Med J 329:15-19 (2004)

36 Importance for Health care provider Industry and Regulatory Agency Type A Type B Adverse Drug Reactions

37 Keep in mind the origin –Advancement in safety heavily relies on reporting of safety events by health care professionals

38 Take Home messages: Adverse Drug Reactions- ADRs Spontaneous ADR monitoring is basis for Pharmacovigilance Pharmacological ADRs is a matter for the local health care provider – quality of care An area for Clinical Pharmacology

39 Take Home messages: Adverse Drug Reaction- a Differential diagnosis An ADR diagnosis: (a minimum an ICD-10 Y 57.9 Ogynnsam effekt av drog eller läkemedel i terapeutiskt bru Submitt an ADR report

40 Thank you for staying till the end!

41 Time for Questions & Answeres If you don ’ t ask stupid question You remain stupid Alvan Feinstein

42 Pharmacovigilance The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems. Source: The Importance of Pharmacovigilance, WHO 2002

43 Causality Assessment Certain Probable Possible Unlikely Unclassifiable