2. دکتر فرهاد گودرزیان نماینده ADR معاونت غذا وداروی اصفهان

3. What is an ideal drug?
In the early 1900s Paul Ehrlich described an ideal drug as a magic bullet. magic bullet. Such a drug would be aimed precisely at a disease site and would not harm healthy tissues.

4. Risk
No medicinal product is entirely or absolutely safe for all people, in all places, at all times. We must always live with some measure of uncertainty.
4/22/2017

5. We Must Always Ask:
Do the potential benefits outweigh the potential risks for this individual?
ACHP

6. Adverse Drug Reaction WHO definition:
Any response to a drug which is Noxious and Unintended, and which occurs at doses used in man for prophylaxis, diagnosis or treatment.

7. تعريف: مطابق تعريف WHO عارضه نا خواسته دارويی عبارتست از:
هرگونه پاسخ ناخواسته وزيان آور که در مقادير مصرف
معمول دارو جهت تشخيص، پيشگيری و درمان بيماری ايجاد شود.

8. History of drug safety after thalidomide eradication
1961 :
Dr William McBride (Australia)( thalidomide 4000 cases)
1964 :
UK started “yellow cards” system
1968 :
start of WHO Programme for International Drug Monitoring

10. Why Should We Learn about Adverse Drug Reactions (ADR)?
Over 2 MILLION serious ADRs yearly
100,000 DEATHS yearly
6.7% of hospitalized patients have an ADR with a fatality of 0.32,
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research

11. Annual death rates in USA
AIDS ,516
Breast cancer ,297
Highway accidents ,458
ADR ,000

12. Costs Associated with ADRs
$ 136 BILLION yearly (related to morbidity and mortality)
Greater than total costs of cardiovascular or diabetic care.
Mean length of stay, cost and mortality ADR patients are DOUBLE that for control group of patients without ADR.
ADRs cause 1 out of 5 injuries or deaths per year to hospitalized patients.
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research

13. ADR has financial and social effects:
1- Unreliability on manufacturer
2- Unreliability on health system
(Physician, Pharmacist & Nurse)
3- Unreliability on governments in saving
the social safety
4- Causing mortality & morbidity

15. Why Are There So Many ADRs?
So many prescriptions!

16. Why Are There So Many ADRs?
Tow-thirds of patients visits result in a prescription
2.8 BILLION outpatients prescriptions were filled in the year 2000 (about 10 prescriptions per person in the U.S.)
ADRs increase exponentially with 4 or more medications
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research

17. Who might get an ADR? Anyone who takes a medicine
Differential diagnosis should include the possibility of an ADR if the patient is taking any form of medication
Things to say
Not all ADRs will be apparent to the patient or the health care professional as ADRs can mimic any disease process. Always be alert to the possibility of ADRs as a cause of the patients symptoms.
Useful information
Quote taken from Edwards IR and Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356:

18. Who is most at risk from ADRs?
Patients who;
are young, or old or female
are taking multiple therapies
50% of patients on 5 drugs or more
have more than one medical problem
have a history of allergy or a previous reaction to drugs
Things to say
Age – The very old and the very young are more susceptible to ADRs. In children, systems for handling drugs are not developed and in the elderly these systems may be slowing with age. The elderly are also likely to have multiple and often chronic diseases. E.g. Elderly patients much more susceptible to the effects of benzodiazepines leading to drowsiness the next day.
Gender – Women appear to be at a higher risk of suffering ADRs. The reason is not clear.
Multiple therapies – The incidence of ADRs increases sharply with the number of drugs taken, 50% patients on 5 drugs are likely to experience an ADR.
Intercurrent diseases – Drug handling may be altered in patients with renal, hepatic, and cardiac disease.
Allergy – patients with a history of allergic disorders are at the greatest risk of experiencing an allergic reaction.
Useful information
Specific diseases predispose to ADRs eg in HIV positive patients there is an increased frequency of idiosyncratic toxicity with anti-infective drugs such as co-trimoxazole (50% vs 3% in HIV negative patients).

19. Older Adults and Medications
Older adults make up 13% of population
Account for:
About 30% of prescribed medications
About 40% of over-the-counter medications
At least 90% take at least one prescription medication
12% use ten or more per week
ACHP

20. Even more, dramatic situation with drug safety is in developing countries (IRAN)
They often have older, cheaper drugs which may be more toxic.
Health professional have less opportunity for post-graduate education on clinical pharmacology.
Useful,easily available, balanced information on adverse effects and their management is absent or not enough.
Ref:World Health Organization

22. Why Should We Report ADRs?!
Assessment the quality of medications
Assessment of drug safety
Detection of occurrence rate of ADR
Decreasing the risk of occurrence of adverse
events

23. How Knowledge About ADRs Is Created?
1-Animal experiments
2- Clinical trials
3- Epidemiological methods
Spontaneous reporting
Cohort studies
Case-control studies

24. Limitations of Clinical Trials
Limited size
Narrow population
Narrow indications
Short duration
Ref: J. Russell May. Adverse drug Reactions and interaction, In: Pharmacotherapy, A pathophysiologic Approach. 1997, Appleton & Lange.

25. How many patients one needs to treat to see with high probability the reaction?
Pre-marketing studies are carried out in limited number of patients: “The law of three”
In order to detect for sure SAE that occurs as 1 event per patients treated we need to treat
6000 patients for 1 case
9600 patients for 2 cases
13000 patients for 3 cases
The number of patients involved in pre-marketing studies has been increasing but is still limited in comparison with the exposure to the drug in post-marketing phase

26. Drug Development

27. Some drugs cause serious ADRs at very low frequencies
bromfenac hepatotoxicity
1 in 20,000 patients,
removed from the market in 1998, less than 1 year after it was introduced).
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research

28. Examples of product recalls due to toxicity
Medicine Year
Thalidomide 1965
Practolol 1975
Clioquinol 1970
Benoxaprofen 1982
Terfenadine 1997
Rofecoxib 2004
Veralipride 2007
Examples of serious and unexpected adverse events leading to withdrawal of medicine
Phocomelia
Sclerosing peritonitis
Subacute nephropathy
Nephrotoxicity, cholestatic jaundice
Torsade de pointes
Cardiovascular effects
Anxiety, depression, movement disorders

29. Spontaneous Reporting
Large population
All medicines
Hospital and out-patient care
Long perspective
Patient analysis possible
Non-interventional
Cheap

30. Pharmaco - Vigilance Pharmaco = medicine Vigilare = to watch
alert watchfulness
forbearance of sleep; wakefulness
watchfulness in respect of danger; care; caution; circumspection
the process of paying close and continuous attention

31. Prevention of ADRs in Human.
Pharmacovigilance
Detection, Assessment
&
Prevention of ADRs in Human.
Ref: World Health Organization.

32. فارماکوويژيلانس به تمام شيوه وروش های ارزيابی و پيشگيری از ADRs گويند.
شناسايی ، ارزيابی ، گزارش عوارض ناخواسته دارويی و
پيشگيری از وقوع آنها در انسان رافارماکوويژيلانس گويند.

33. Recent trends: enlarging the scope of pharmacovigilance
Pharmacovigilance concerns have been widened to include:
herbal medicines
traditional and complementary medicines
blood products
biologicals
vaccines
medical devices

34. Pharmacovigilance Major Aims
Early detection of unknown reactions and interactions
Detection of increase in frequency
Identification of risk factors
Quantifying risks
Preventing patients from being affected unnecessarily
RATIONAL AND SAFE USE OF DRUGS
Ref: World Health organization.

35. The ultimate goal of pharmacovigilance is improving pharmacotherapy Ref:World Health Organization

37. CASE STUDY 6
پ-م خانم 38 ساله با وزن 55 کیلوگرم است که به علت سردرد شدید به همراه تهوع واستفراغ به اورژانس بیمارستان مراجعه نموده است.در شرح حال بیمار عنوان می نماید که سردردش ازحدود 8روز پیش آغاز گردیده وبه تدریج میزان سردرد افزایش یافته به طوری که دیگر قابل تحمل نبوده است. در سابقه مصرف دارو بیمار تنها سابقه مصرف قرص LD را جهت پیشگیری از بارداری از 9 ماه پیش اعلام می دارد وسابقه ای از عارضه دارویی قبلی یا بیماری خاصی را ذکر نمی نماید.با توجه به اینکه بیمار از زرین شهر مراجعه نموده و از قرص شرکت بهبود با شماره ساخت استفاده نموده فرم زرد را تکمیل نمایید.

38. OCPعوارض شایع ترین: سردرد- سرگیجه - تهوع – بی نظمی در خونریزی قاعد گی
مهم ترین: ترومبوآمبولی – آمبولی ریه – ایست قلبی عروقی – پانکراتیت – تومور کبدی – انفارکتوس میوکارد – ترومبوز کرونر – خونریزی مغزی – هیپرتانسیون – بیماریهای صفراوی – تومور کبدی
نیاز به تماس به پزشک : احساس درد یا فشار در قفسه سینه – بی حسی یا سفت شدن پا – درد در پا یا باسن – تنگی نفس – سردرد شدید – اختلا ل بینایی – ترشح یا خونریزی غیر عادی از واژن – احساس وجود تود ه درسینه ها یا درد شدید شکم

40. The FDA Safety Information and Adverse Event Reporting Program:
MedWatch
The FDA Safety Information and Adverse Event Reporting Program:
Safety alerts
Recalls
Withdrawals
Important labeling changes
Biologicals, Drugs, Dietary supplements

41. از توجه شما متشکرم