Download Dr. Mary Teeling Dept. of Pharmacology & Therapeutics / Centre for

ADVERSE DRUG
REACTIONS
Mary Teeling
27 April 2009
Did you know that
• In U.S. ADRs cause an estimated 100,000
deaths per year
• Up to 5% of all hospital admissions are
due to ADRs
• 30% of hospital patients suffer an ADR
This is huge cause of iatrogenic disease.
What is meant by the term “Adverse
Drug Reaction (ADR)?
Adverse (Drug) Reaction
(ADR)
Defined as:
a response to a medicinal product which is noxious
and unintended and which occurs at doses
normally used in man for the prophylaxis,
diagnosis or therapy of disease or the the restoration,
correction or modification of physiological function.
• Not due to overdose or drug abuse
• Causal relationship between the drug and the
response is suspected, but not necessarily proven
In plain english…
• An ADR is an unwanted, adverse
occurrence (e.g. skin rash, GIT problems
etc) in a patient which you suspect might be
caused by a drug the patient has taken
Serious Adverse Drug Reaction
Defined as: Serious adverse reaction means an adverse
reaction which results in death, is lifethreatening, requires inpatient
hospitalisation, or prolongation of existing
hospitalisation, results in persistent or
significant disability or incapacity, or is a
congenital anomaly / birth defect.
Unexpected ADR
This is a suspected ADR that is not listed in
the prescribing information ( Summary of
Product Characteristics) of a medicine.
NOT ALL ADRS ARE KNOWN ABOUT
A DRUG AT TIME IT IS LICENSED
Adverse Event (AE)
Defined as: An undesirable experience occurring
following administration of a “medicinal
Product”
An adverse event does not necessarily have a
“causal relationship” with a medicine
Why do ADRs occur?
Most ADR’s are
• Predictable i.e. based on pharmacological
action of the drug
• Dose-dependent
• May be preventable / avoidable
(“Type A” or “pharmacological” ADR’s make
up 80% of ADRs)
Examples of Type A reactions
Warfarin or
Aspirin
Excessive
bleeding
Beta blockers
cold hands and feet
Cytotoxic Agents
(anti-cancer)
Myelosuppression
Type B Reactions
These may be known as “idiosyncratic” / “bizarre”
These are
• not predictable from pharmacological action of
drug
• often
– serious
– dose-independent
• may be immune-mediated (e.g. IgE mediated
hypersensitivity reactions)
[Type C Reactions]
Includes
• Increased rate of disease being treated with drug
– arrhythmias with use of anti-arrhythmic agents
– suicide in depressed patients on anti-depressants
• Increased rate of “spontaneous” disease in specific
populations
– increased rate of vaginal cancers in daughters of
women who received stilboestrol during pregnancy –
20 year time lapse
**Not predictable, often hard to detect but
pharmacovigilance may pick them up eventually**
Pharmacogenomics
This is the study of how an individual’s genetic
inheritance affects his / her response to drugs
Genetic polymorphisms of several enzyme
systems have already been elucidated
Affecting
• Cytochrome p450 systems (e.g.CYP2D6)
• Functional Enzymes (e.g. ACE)
This may impact on development of ADRs in future - ?how
Risk factors for ADR’s
•
•
•
•
Extremes of age
Health status (liver/renal disease)
Concomitant drug use (“polypharmacy”)
Female gender (?)
But remember ADR’s can occur in the
absence of any of these!
What drugs cause ADR’s
All drugs can!
Important areas for prescriber:
• Drugs with a narrow TI / therapeutic index
(cytotoxics, anti-epileptic agents)
• Most commonly used drugs (NSAIDs,
Cardiac drugs – greater exposure)
• Drugs in combination (e.g. diuretics and
digoxin, warfarin and NSAIDs)
How to diagnose ADR’s (1)
Should include ADR in differential diagnosis
of disease state (e.g. liver disease, skin rash,
G.I. bleeding)
Check out
• Drugs that patient has been prescribed
• Drugs that patient is actually taking!
• Clarify dose, dosing interval
• Always ask for OTC / herbal medicine
(remedy) usage
How to diagnose ADR’s (2)
Check out
• Exact nature of disease state / reaction
• Possible temporal relationship with drug
exposure
• Past history of similar events with other /
similar drugs
• Perform relevant laboratory tests (LFT’s,
FBC and Blood film)
• “Dechallenge” versus “rechallenge” -??
How to manage ADR’s
Serious
• Need to treat
symptoms urgently
(e.g. anaphylaxis)
• Need to discontinue
drug
• Warn patient for
future
Non – serious
• Treat symptoms as
appropriate
• Decision to withdraw
depends on ADR,
underlying disease,
availability of
alternative therapy
(cytotoxics)
Question
A 70-year old is knocked down by a car, 4
days after starting a new drug treatment for
hypertension
? Is this an ADR or AE?
Answer
Well it could be ADR!
Did she stumble in front of the car due to
hypotension / altered consciousness / ataxia
/ other CNS effects from the drug?
Or was the driver at fault?
What to do with this lady (1)
• History of event very important as is
history of how she has been since starting
the medicine
– Symptoms of postural hypotension
– Feelings of unsteadiness
– Any new / unusual symptoms since starting the
drug
– Does she remember the event
What to do with this lady (2)
Check for hypotension / postural hypotension,
any signs of unsteadiness
Check the prescribing information for similar
reports of unsteadiness etc
Remember
Just because it is not listed doesn’t mean that
the drug is not to blame
If in doubt report to the regulatory authorities
Reporting ADRs
All suspected reactions can be reported (i.e.
don’t need absolute certainty that this is an
ADR) to the
Remember Irish Medicines Board (IMB)?
Responsible for collecting information on ADRs
in Ireland from healthcare professionals and
acting on the information as appropriate
Why Report ADRs?
• Part of Pharmacovigilance (defined as the
ongoing monitoring of safety of medicines
in the marketplace i.e. real-life usage in the
interest of public health)
• ADR reporting (“spontaneous reporting”)
invaluable for picking up previously
unknown ADR’s i.e. not identified in
clinical trials
Why Report ADRs?
• Can identify problems with faulty batches of
biological or biotechnological medicines
(remember HIV and HCV with blood products)
• Can identify hitherto unknown ADRs in special
populations (e.g. our 70-year lady)
• Can identify hitherto unknown problems with
teratogenicity / longterm ADRs
**Type B & C reactions usually only identified
by pharmacovigilance**
Remember: • Majority of ADRs are predictable and due
to the pharmacological action of the drug
• Certain patient characteristics may
predispose to ADRs
• Prescribing information on each drug gives
details of contraindications and special
precautions for use
• Pharmacogenomics may help to further
elucidate susceptibility to ADRs in future
Sources of Information on
ADRs
• Irish Medicines Board www.imb.ie
• Prescribing information (Summaries of
Product Characteristics) at
www.medicines.ie; www.imb.ie
• National Medicines Information Centre
www.nmic.ie
Questions?