Iran ADR Centerپارسائيدكتر
گروه فارماكولوژي دانشكده پزشكي
&&
ADR(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.
هر گونه پاسخ داروئي مضر و
نامطلوبي كه با دوز معمولي دارو
در انسان جهت پيشگيري، تشخيص
و يا درمان ايجاد شده باشد
:اصطالحات رايج
*Side Effects عوارض كم اهميت ومختصر
* Adverse Reaction عوارض مهم و كامال ناخوشايند
* Toxicity ( اثرات سمي مستقيم دارو )غالبا دوز باال
* Secondary Effects آثار ثانوي غيرمستقيم
* Intolerance عدم تحمل بدليل آستانه پايينپاسخ دهي
* Idiosyncrasy پاسخ غير نرمال بدليلاختالل ژنتيكي
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
Annual death rates in USA
AIDS 16,516 Breast cancer 42,297
Highway accidents 43,458
ADR 100,000
percentage of hospital admissions due to ADR:
USA 28%UK 15.6%France 12.6%Norway 11.5%
Costs Associated with ADRs
$ 136 BILLION yearly (related to morbidity and mortality)
Greater than total costs of cardiovascular or diabetic care.
The total cost of drug-related morbidity and mortality exceeds the cost of the medications themselves.
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
The cost of adverse drug events: estimated lost patient activity days per year in hospitalised patients
Country Serious ADRs Lost Activity Days
US 700,000 1,218,000 Germany 206,000 358,440
UK 148,000 257,520 Australia 48,000 83,520
Sweden 22,000 38,280
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
ADR has financial and social effects:
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
So many prescriptions!
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
طبقه بندي عوارض (A-E) جانبي
انواع فرعي:
(Continuos) Cنوع •
( Delayed) D نوع •( Ending of use) E نوع•
انواع اصلي:
(Augmentedنوع •
A)
(Bizarre) Bنوع •
AB
-+قابل پيش بيني •-+وابستگي به دوز•كمزيادميزان شيوع•زيادكممرگ و مير•قطع تنظيم دوزدرمان•
مصرف
Aمقايسه عوارض جانبي نوع Bو
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
چگونه يك عارضه
جانبي به
دارو نسبت داده ميشود؟
شرايط ارزيابي ارتباط عارضه
جانبي با داروارتباط منطقي بروز عارضه با - 1
زمان مصرف دارو
- ارتباط عارضه با خصوصيات 2 شناخته شده دارو
- رفع عارضه با قطع مصرف دارو 3
- عود عارضه با شروع مصرف 4 مجدد دارو
- توجيه منطقي ارتباط عارضه با 5 يا ...بيماري مريض
بجانبيعارضهارتباطبررسي داروا
5 4 3 2 1 ارزيابي ارتباط0 + + + + Definit قطعي
_ 0 + + + احتمالي
Probable + 0 0 + + Possible ممكن
_ 0 0 _ + مشروط
Conditional0 0 0 0 0 غير قابل بررسي
Unassessable + 0 0 0 _
Unlikely غیر محتمل
Detection, Assessment,
Prevention of ADRs in Human.
Ref: World Health Organization.
اهداف اصلي فارماكوويژيالنس
شناسائي زودهنگام واكنشهاي ناشناخته •داروئي
تعيين ميزان افزايش در بروز عوارض•شناسائي فاكتورهاي خطر•ارزيابي كيفي مخاطرات•پيشگيري از بروز مخاطره غير ضروري در •
بيمارمصرف منطقي و سالم داروها•
The ultimate goal of pharmacovigilance is
improving pharmacotherapy
Ref:World Health Organization
تاريخچه فارماکوويژيالنس
:1968 سال • توسط سازمان مللDrug Monitoringشروع برنامه
(: 1848 سال قبل )160 حدود • کلروفرم ساله در بيهوشي با 15 فوت جوان
)جراحي ناخن پا( بعلت فيبريالسيون بطني
عاري از هر گونه و خالص ”فراورده هاي داروئي بايد بيانيه:
باشند“ آلودگي :1936 سال•بعنوان دي اتيلن گليکول مورد مرگ ناشي از 107
:1961 سال •حالل سولفوناميدتاليدوميد مورد نقص عضو ناشي از 4000گزارش
:1964 سال •از استرالياشروع استفاده از سيستم کارت زرد در انگليس
Drug Classes Responsible for ADRsDrug Class FrequencyAntibiotics Most frequent
Antitumor agents
Anticoagulants
Cardiovascular agents
Anticonvulsant agents
Antihypertensives
Analgesics
Antiasthmatics
Sedative/hypnotics
Antidepressants
Antipsychotics
Peptic ulcer therapy Least frequentRef: J. Russell May. Adverse Drug Reactions and Interactions, In: Pharmacotherapy, A pathophysiologic Approach. 1997,
Appleton & Lange.
Types of Drug-Related Effects by Frequency
Type of adverse event Frequency Marrow suppression Most frequentBleeding Central nervous systemAllergic/cutaneousMetabolicCardiacGastrointestinalRenalRespiratory Least frequent
Ref: J. Russell May. Adverse Drug Reactions and Interactions, In: Pharmacotherapy, A pathophysiologic Approach. 1997, Appleton & Lange.
• Patient’s specification
• Patient’s drug history
• Pharmacology of prescribed drugs
• Prescription of minimum effective
dosage
Preventing ADR
Over 75% of all ADR are dose-dependent
Dosage of many drugs widely different
to individual needs.
Ref:World Health Organization
Essential factors causing ADRs:
Route of administration Dosage Duration of treatment Problems with drug:
1-Formulation
2-Problems with preparing of drug
Factors related to drug:
Sex Age (weight) Genetic (PHARMACOGENOMICS) Drug allergy Lack of knowledge in patientsConcomitant drugs
Factors related to patient:
Essential factors causing ADRs:
Non-compliance - underestimated
Route of Administration - bioavailability
Food - protein malnutrition
Pollutants - smoking/herbicide residues
Timing - chronopharmacology
Factors related to patient (Cont):
فوايد وجود ADR در بيمارستان برنامه
افزايش كيفيت درمان -1جلوگيري از شكايات حقوقي -2
ارزيابي مشكالت دارويي -3ارزيابي مشاهدات پزشكان و ديگر -4
حرف پزشكيارتقاء دانش دارويي دست -5
اندركاران درمان
داليلي كه باعث كاهش ميگردد:ADRگزارشات
عدم اطالع از مكانيزم موجود براي -1ارسال گزارش
عدم دسترسي به فرم مربوطه -2عدم اهميت عارضه از نظر گزارشگر -3
نداشتن وقت -4فرم مربوطهتكميل در رابطه با -5
اجتناب از درگيري در كارهاي اداري -6ترس از شكايات حقوقي, كيفري -7
ADR- عدم اطمينان از بوجود آمدن8 توسط دارو
Drugs cause hospitalization
Digoxin 41 Aspirin 25
Aspirin 24 Digoxin 24
Prednisone 15 Warfarin 12
Warfarin 9 Prednisone 8
Guanethidine 5
The numbers of reports, registered in ADR center of Iran
The numbers of reports, registered in ADR center of Iran
•From the year 1377 to Mordad 83 , 5861 cases of Adverse Drug
Reaction have been sent to Iranian ADR Center
1837 1793
734671
446
17 7
276
730
200
400
600
800
1000
1200
1400
1600
1800
2000
Pharm
acis
t
Genera
l pra
ctiti
oner
Special
ist
Nurse
Patie
nts
Dentist
Clinic
al p
harm
acis
t
Oth
ers
Unknown
Reporters
Diclofenac Na Above 100 Cases of Foot drop
Withdrawal from Iranian Pharmacopoeia
Streptokinase
Tramadol?
• From 04.81 to 05.83, 289 cases of adverse effects of Tramadol have reported to ADR center
• Among them :
81 cases have been in Male
&
208 cases have been in Female
Adverse Reaction of Tramadol from 04.81 to 03.83
6 Major Adverse Effects of Tramadol:
•Nausea 125•Vomiting 116•Vertigo 109•Asthenia 57•Dyspnea 42
•Hypotension 41
84.78%
9.34%5.19%
0.35%
0.35%
IM PO IV ID Unknown
Rout of administration(In patients with Tramadol adverse effects)
Bupivacaine
4 Cases of Para-plegia following IT injection
2 of them led to Death
Sildenafil
•Sildenafil has cardiac related side effect.
•Some cases of myocardial infarction were reported to ADR center due to this
drug.
www.fdo.ir
دارو و غذا معاونت
كاربردی تحقيقات دبيرخانه
دارويی ناخواسته عوارض بررسی و ثبت مركزIranian Adverse Drug Reaction Monitoring
Center
ADRمركزمعرفي • ADR فرم• عضويت• ها • اطالعيهخبرنامه• مركز • ADRگزارشاتمفيد • لينكهای
مركز ثبت و بررسي عوارض ناخواسته داروها
دفتر تحقيق و توسعه-معاونت غذا و دارو
وزارت بهداشت درمان و آموزش پزشكي
6405569تلفن:6417252نمابر:
E-mail: [email protected]
Report of Iranian ADR monitoring center
Official member countriesAssociate member countries
WHO Drug Monitoring ProgrammeParticipating countries 1999
58 countries have joined the programme
-
International Vigilance
Every healthcare professional in the world should be constantly alert for adverse effects or potentional new
hazards and reporting them to their National Centers.
Countries with the best reporting rates generate:
• Over 200 reports per 1,000,000 inhibitants per year.
• Over 150 reports per 1000 physicians per year.
1720
1502
601
469 448
281 235 205112
63 61 57 49 45
0
200
400
600
800
1000
1200
1400
1600
1800
Adverse Drug Reaction vs Drug classes
From:
1377
To
Mordad 83
691
352
223 212
96 90 88 8252 49 40 40 25
0
100
200
300
400
500
600
700
CNS
GI
Body as a whole
Skin & apprndages
Application site
Cardiovascular
Psychiatric
Respiratory
Autonomic
Musculoskeletal
Urinary
Vision
Heart rate & rhythm
Site of Reaction )CNS agents (
From:
77
To
Mordad 83
Site of Reaction (Antibiotics)
596
347
179 167
71 6126 21 18
0
100
200
300
400
500
600
Skin &
Appendag
es GI
Body as
a whole
CNS
Respira
tory
Liver &
bili
ary
Visio
n
Coagula
ting S
ys
Reproduct
ive
From:
77
To
Mordad 83
0-10 3 11-20 7 21-30 86 31-40 61 41-50 51 51-60 29 61-70 18 71-80 11 >80 3 Unknown 20
Age groups Age groups )Reaction of Tramadol(:)Reaction of Tramadol(:
Adverse effects of Tramadol from 04.81 to 03.83
Reaction Number Reaction Number
Sweating 24 Myalgia 7
Headache 21 Pale 7
Agitation 20 Ataxia 6
Somnolence 17 Vision disorders 6
Pruritus 16 Paraesthesia 6
Rigors 15 Injection site reaction 6
Flushing 11 Delusion 6
Urticaria 11 Tachycardia 6
Bronchospasm 10 Respiratory depression 6
Hallucination 9 Palpitation 5
Convulsion 9 Rash 4
Hypertension 8 Cold extremity 4
Confusion 8 Apnoea 3
Abdominal pain 8 Anxiety 3
Dry mouth 7 Stupor 3
Reaction Number Reaction Number
Cardiac arrest 3 Back pain 1
Anorexia 3 Arrhythmia 1
Shock 3 Bradycardia 1
Allergic reaction 2 Lacrimation abnormal 1
Cyanosis 2 Myocardial Ischemia 1
Constipation 2 Diarrhea 1
GI disorders 2 Depression 1
Leg pain 2 Erythem 1
Dysphagia 2 Coma 1
Speech disorders 2 Edema 1
Urinary retention 2 Hearing decrease 1
Chest pain 2 Facial pain 1
Fever 2 Withdrawal syndrome 1
Syncope 2 Foot drop 1
Insomnia 2 Tremor 1
Adverse effects of Tramadol from 04.81 to 03.83
The following tips must be reminded when using Sildenafil:
• Cardiovascular adverse effects such as atrial fibrillation, cardiomyopathy, flushing, hypotension, myocardial infarction, thrombosis, ventricular tachycardia have been reported with Sildenafil.
• Concomitant use of Sildenafi with following drugs are forbidden:
Organic nitrates (eg. Nitroglycerin) Nitrates & Nitric donors (eg. Nitroproside)
Lamotrigine
Common adverse effects:
Skin reaction: rash ,Steven's Johnson
syndrome, TEN
Women more than men Onset Caution Adverse events causing hospitalization Weight limitation
Age Limitation
• Not effective & safe in children under 16 years old
• Person younger than 16 years old:
• Risk factor for severe skin reactions
Lindane
•*This drug has entered to the world drug market since 1901.
•*Since the year 1990 Lindane has been introduced as a second line treatment.
Suggestion:
Single dose of useSecond line of treatmentLabelingContraindicationPrecaution
•Systemic adverse effects of Lindane•70% of adverse effects have been the CNS adverse events,including:•Seizure,Vertigo,Headache,Parasthesia
•17 cases of death have been reported to FDA,•IN 3 cases an established relationship between the events and using of drug were found
FDA alert (2003)FDA alert (2003)
CelecoxibLabelling Changes
• Celecoxib Long-term Arthritis Safety Study
(Class) did not show a safety advantage of
upper GI events for celecoxib compared with
diclofenac or ibuprofen.
Hypiran
Drug Interaction with:
• Indinavir• OCPs• Antidepressants• Digoxin, Warfarin, Theophylline, Cyclosporin
Risperidone
Extrapyramidal Reactions:
Rabbit Syndrome
1 Case in the USA 2 Cases in the English- Language Literature 4 Cases reported to IADRMC
.
IV IG
2 Cases of Death2 Cases of Death
following Administration of Vials with Unusual Colorfollowing Administration of Vials with Unusual Color
Benzyl benzoate
.
5 Cases of Sever Systemic Side Effects 5 Cases of Sever Systemic Side Effects following Topical Administration following Topical Administration
3 of them led to Death3 of them led to Death
The FDA Safety Information and Adverse Event Reporting Program:
Safety alerts Recalls WithdrawalsImportant labeling changesBiologicals, Drugs, Dietary supplements
MedWatch
www.fda.gov/medwatch/www.fda.gov/medwatch/
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