Transcript (ADR)?

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.
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.
4/3/2016
We Must Always Ask:
• Do the potential
benefits outweigh the
potential risks for
this individual?
ACHP
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.
‫تعريف‪:‬‬
‫مطابق تعريف ‪ WHO‬عارضه نا خواسته دارويی عبارتست از‪:‬‬
‫هرگونه پاسخ ناخواسته وزيان آور که در مقادير مصرف‬
‫معمول دارو جهت تشخيص‪ ،‬پيشگيری و درمان بيماری ايجاد‬
‫شود ‪.‬‬
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
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
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
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
So many prescriptions!



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
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
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
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
How Knowledge About
ADRs Is Created?
1-Animal experiments
2- Clinical trials
3- Epidemiological methods
 Spontaneous reporting
 Cohort studies
 Case-control studies
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.
Clinical development of medicines
Drug Development
Phase I
20 – 50 healthy volunteers
to gather preliminary data
250 – 4000 more varied
patient groups – to
determine short-term safety
and efficacy
Phase II
Phase IV
150 – 350 subjects with
disease - to determine
safety and dosage
recommendations
Post-approval studies to
determine specific safety issues
Preclinical
Animal
Experiments
Phase I
Development
Phase II
Regi
strat
ion
Animal experiments for
acute toxicity, organ
damage, dose dependence,
metabolism, kinetics,
carcinogenicity,
mutagenicity/teratogenicity
Phase III
Phase III
Phase IV
Spontaneous
Post-approval Reporting
Post Registration
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 2000 patients treated we need to treat
• 6000 patients
• 9600 patients
• 13000 patients
for 1 case
for 2 cases
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
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
 Assessment the quality of medications
 Assessment of drug safety
 Detection of occurrence rate of ADR
 Decreasing the risk of occurrence of adverse
events
Spontaneous Reporting
Large population
All medicines
Hospital and out-patient care
Long perspective
Patient analysis possible
Non-interventional
Cheap
Examples of product recalls due
to toxicity
• Medicine
• Thalidomide
1965
• Practolol
• Clioquinol
• Benoxaprofen
1982
• Terfenadine
• Rofecoxib
• Veralipride
Year
1975
1970
1997
2004
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
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
Detection, Assessment
&
Prevention of ADRs in Human.
Ref: World Health Organization.
‫فارماکوويژيالنس‬
‫• به تمام شيوه وروش های ارزيابی و پيشگيری از ‪ ADRs‬گويند‪.‬‬
‫• شناسايی ‪ ،‬ارزيابی ‪ ،‬گزارش عوارض ناخواسته دارويی و‬
‫پيشگيری از وقوع آنها در انسان رافارماکوويژيالنس گويند‪.‬‬
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.
The ultimate goal of pharmacovigilance is
improving pharmacotherapy
Ref:World Health Organization
Case #11: 34 yo female with DM, Hypertension,
depression and recent UTI, taking metformin, insulin,
lisinopril, paxil and ciprofloxacin. Presents with
severe calf pain and difficulty with plantar flexion
What is the most likely cause?
A) Peroneal Nerve Palsy
B) Diabetic Neuropathy
C) Transient ischemia event
D) Achilles Tendon Rupture
Case #11 (cont). Which medication
is the most likely cause?
A)
B)
C)
D)
E)
Metformin
Lisinopril
Paxil
Ciprofloxacin
Insulin
Achilles Tendon Rupture
• Thompson Test
Misconceptions about ADR Reporting

All serious ADRs are documented by the time a drug is
marketed

About patient receiving multiple medications,it is difficult
to determine if a drug is responsible for the ADR

ADRs should only be reported if absolutely certain

One reported case can’t make a different
 Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
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.
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.
‫جهت دریافت اطالعیه های ‪ADR‬‬
‫‪• www.fdo.mui.ac.ir‬‬
SEND A REPORT
SAVE A LIFE
Dr. Goodarzian
MedWatch
The FDA Safety Information and Adverse
Event Reporting Program:
www.fda.gov/medwatch/
Safety alerts
Recalls
Withdrawals
Important labeling changes
Biologicals, Drugs, Dietary supplements
‫ازتوجه شما متشکرم‬