The Yellow Card Scheme: Reporting Adverse Drug Reactions

1. The Yellow Card Scheme: Reporting Adverse Drug Reactions www.yellowcardwales.org

2. What is an adverse drug reaction? An adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug. www.yellowcardwales.org

3. Type A (Augmented) Pharmacological Dose-related Predictable and common Discovered before marketing Type B (Bizarre) Hypersensitivity or idiosyncratic Not dose-related Unpredictable and rare Discovered after marketing Classification www.yellowcardwales.org

4. Classification of ADRs • Type C (`Chronic treatment effects’) • osteoporosis with steroids • Type D (`Delayed effects’) • drug induced cancers • Reports of skin cancers, lymphomas and other cancers following topical pimecrolimus and tacrolimus • Type E (`End of treatment effects’) • withdrawal syndromes • Headache, anxiety, dizziness, sleep disturbances, gastro-intestinal disturbances after stopping paroxetine. www.yellowcardwales.org

5. Classification of ADRs • Type F (`Failure of therapy’) • unexpected failure of therapy due to drug interaction • St Johns Wort reducing efficacy of combined hormonal contraceptives • Type G (Genetic or genomic) • Irreversible genetic damage • Carcinogens • Genotoxins • Teratogens www.yellowcardwales.org

6. Why are ADRs important? • Major clinical problem – increase morbidity and mortality. • ADRs are related to 6.5% hospital admissions in adults, and 2.1% in children 2 • 6.7% hospitalised patients suffer`serious’ ADRs 1 • 0.15% of hospital patients suffer fatal ADRs (= 5700 deaths per year) 1,2 • ADRS are 4th leading cause of death in the USA 1 • Increase hospital stay. ADRs result in the use of seven 800 bed UK hospitals per year.2 • Financial burden on NHS £466m 2 • Up to 40% patients in the community experience ADRs 3 1 Lazarou J, Pomeranz BH, Corey PN. Incidence of ADRs in hospitalised patients. JAMA .1998; 279: 1200-1205. 2 Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004; 329(7456):15-9. 3 Martyrs C. Adverse reactions to drugs in general practice. BMJ 1979; 2: 1194-1197 www.yellowcardwales.org

7. ADRs can also… • Adversely affect patient compliance • Reduce available choice of drug treatment • Reduce potential efficacy of drug treatment • Reduce quality of life • Cause diagnostic confusion • Reduce a patient’s confidence in their healthcare professional(s) www.yellowcardwales.org

8. Who is most at risk from ADRs? • The elderly • Children • Co-existing diseases • Females • Atopic individuals • Polypharmacy • 50% of patients on5 drugs or more www.yellowcardwales.org

9. What should raise your suspicion? • Timing with drug treatment. • Abnormal clinical measurements while on drug therapy e.g. B.P, temp, pulse, blood glucose and weight • Abnormal laboratory results while on drug therapy. Could be biochemical or haematological • New therapy started which could be used to treat ADR • Patient risk factors • Listen to patients own concerns www.yellowcardwales.org

10. Assessing causality • Nature of the reaction • Timing • Relationship to dose • Other possible causes for the symptoms • Improvement when drug(s) stopped • Has reaction been reported before • Dechallenge/Rechallenge www.yellowcardwales.org

11. The Yellow Card Scheme • Introduced in 1964 after thalidomide tragedy • Spontaneous reports of suspected adverse drug reactions. • Acts as an early warning system to identify ADRs and risk factors • Over 600,000 confidential reports have been received in UK • MHRA can detect duplicate reports www.yellowcardwales.org

12. Why report ADRs? • Important role in patient safety • Allows continual safety monitoring of drugs • old & new • New drugs - lack of experience on adverse effects • Exposure in about 1500 people only • Short duration • Unlikely to detect ADRs • Less frequent than 1/1500 • With long latency • Lack of experience in special patient groups • Elderly, children, pregnancy, multiple disease, polypharmacy • To detect rare adverse effects www.yellowcardwales.org

13. Strengths of Yellow Card Scheme • Acts as ‘early warning system’ for identification of previously unrecognised reactions • Provides information about factors which predispose patients to ADRs • Allows comparisons of ADR ‘profiles’ between products within same therapeutic class • Continual safety monitoring of a product throughout its life span as a therapeutic agent www.yellowcardwales.org

14. Weaknesses of Yellow Card Scheme • Cannot provide estimates of risk as • true number of cases is underestimated • total number of patients exposed is unknown • Relies on ADR being recognised • Not all ADRs are reported • Only 10% serious reactions reported • May be stimulated by promotion and publicity • Reporting high for newly marketed drugs and falls off over time • Reports do not imply causality www.yellowcardwales.org

15. Why are reporting rates low? • Too busy • Not sure what to report • Uncertain of the threshold for a serious reaction • Not easy to find a Yellow Card • Not my responsibility • It takes too long to complete a card • Reporting generates too much extra work • Duplication • Belief that serious ADRs will be identified in clinical trials • Confidentiality www.yellowcardwales.org

16. Completing a Yellow Card www.yellowcardwales.org

17. Simple Fast Drop-down menus Allows reporter to register on the site The Yellow Card can be saved at any time Link from clinical systems tab on ABMU intranet Online www.yellowcard.mhra.gov.uk www.yellowcardwales.org

18. On Paper • Available in BNF, MIMs, ABPI • Available from YCC Wales • Download from MHRA website www.yellowcardwales.org

19. What to report • Report all suspected adverse drug reactions for • new drugs (marked ▼) - even if mild • established drugs that are serious - even if wellrecognised • Serious reactions include those which are fatal, life-threatening, disabling or incapacitating, result in or prolong hospitalisation, congenital abnormalities or medically significant • Vaccines • Unlicensed medication • Herbal medicines Causality does not need to be established www.yellowcardwales.org

20. Black triangle drugs▼ • ▼indicates that the CHM/MHRA are intensively monitoring that product • ▼will be assigned to a product because:- • the drug is new to the UK market • the drug is being administered to the patient either by a new route of administration or a new formulation which is considered may have an impact on the already established risk/benefit profile of that drug • the drug is being administered for a new indication www.yellowcardwales.org

21. If you suspect an ADR… • Do not assume someone else will report it • Only 2-4% of all ADRs are reported • Only 10% of serious suspected ADRs are reported • Do you have to be completely certain that what you have seen is an ADR? No www.yellowcardwales.org

22. Information to include on a Yellow Card • 4 critical pieces of information that must be included on the report :- • Suspected drug(s) • Suspect reaction(s) • Patient details • Reporter details www.yellowcardwales.org

23. Patient Details • Sex of the patient • Age at time of reaction • Weight if known • Do not need to know name or DOB as this could identify patient and break patient confidentiality • Patients initials and local identification number (hospital or practice number) which will identify patient to you in the event of future correspondence www.yellowcardwales.org

24. Reporter details • Must be completed in all cases • Name and full address • Need to acknowledge receipt of report and follow up further information if necessary. • Profession • Specify “hospital pharmacist” www.yellowcardwales.org

25. Additional Useful Information • Other medication in the last three months including herbal and over the counter meds. • Use additional sheets if necessary. • If no other meds are being taken or if no more information is available say so • Include details of any: • rechallenges • relevant medical history • test results • known allergies • suspected drug interactions www.yellowcardwales.org

26. How is the Yellow Card data used to improve patient safety? • Changes to SPC e.g. restriction in use, special warnings and precautions • Publication of Drug Safety Update • Issue of ‘Dear Healthcare professional’ letters • Drug Analysis Prints (DAPs) • Withdrawal of a medicines if patient safety is threatened www.yellowcardwales.org

27. Published monthly Register for alerts http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/index.htm Drug Safety Update www.yellowcardwales.org

28. Examples of ADRs identified by Yellow Card Scheme • Domperidone - risk of cardiac side-effects • Use restricted to N + V indication • Limited duration • Voriconazole – liver toxicity • Strontium ranelate – risk of cardiac side-effects • CI in those with cardiac problems • Use restricted to pts with severe osteoporosis, last resort • Risks of switching between branded and generic anti-epileptics www.yellowcardwales.org

29. Where to find ADR information • Reference texts • British National Formulary (BNF) • Summary of Product Characteristics (SPC) • Martindale • Lee’s textbook Adverse Drug Reactions • Journals • Adverse Drug Reaction Bulletin • Drug Safety Update • Medline/Embase/Pharmline search • Electronic sources • Micromedex • www.mhra.gov.uk • Meyler’s 'The Side effects of drugs www.yellowcardwales.org

30. “All health-care professionals have a responsibility to inform colleagues about clinically important adverse drug reactions that they detect, even if a well-recognised or causal link is uncertain.” • Document in notes if yellow card completed • Edwards IR and Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356: 1255-59 www.yellowcardwales.org

31. If you suspect an ADR…. do not assume someone else will report it! www.yellowcard.mhra.gov.uk www.yellowcardwales.org