ADVERSE DRUG REACTION

Chau Thi Anh Minh

DI&ADR Regional Center
Choray Hospital
 Content
• Definition
• Classification of adverse drug reactions
• Preventing adverse drug reactions
• Identifying susceptibility
• Treatment plan
• Diagnosing adverse drug reactions
• Pharmacovigilance
• Reporting of adverse drug reactions
• Managing adverse drug reactions
 Definition
• Adverse drug events (ADEs) as any injuries resulting from medication use,
including physical harm, mental harm, or loss of function [7].
• Medication errors refer to any mistakes occurring in the medication use process,
regardless of whether an injury occurred or whether the potential for injury was
present. Approximately 1 in 100 medication errors result in an ADE, while 7 in 100
have the potential to do so.
• Preventable ADEs are ADEs resulting from a medication error that can be
avoided. At least a quarter of all medication-related injuries are preventable .
• Adverse drug reactions (ADRs) – unintended, harmful events attributed to the use
of medicines – occur as a cause of and during a significant proportion of
unscheduled hospital admissions.

Gandhi TK, Seger DL, Bates DW. Identifying drug safety issues: from research to practice. Int J Qual Health Care 2000; 12(1):69-76. By permission of Oxford University Press.
Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 1995;
274:29.
Wittich CM, Burkle CM, Lanier WL. Medication errors: an overview for clinicians. Mayo Clin Proc 2014; 89:1116.
Bates DW, Boyle DL, Vander Vliet MB, et al. Relationship between medication errors and adverse drug events. J Gen Intern Med 1995; 10:199.
Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016;16(5):481-485. doi:10.7861/clinmedicine.16-5-481
 Classification of adverse drug reactions
• Type A reactions – sometimes referred to as augmented reactions – which are
‘dose-dependent’ and predictable on the basis of the pharmacology of the drug
• Type B reactions – bizarre reactions – which are idiosyncratic and not predictable
on the basis of the pharmacology.

Rawlins MD. Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, editor. Textbook of adverse drug reactions. Oxford:: Oxford University Press; 1977. p. 10
 Classification of adverse drug reactions
• ‘DoTS’
• classifies reactions dependent on
the Dose of the drug,
the Time course of the reaction
 and relevant Susceptibility factors (such as genetic, pathological and other
biological differences)
• advantage of being helpful to consider the diagnosis and prevention of ADRs in
practice.

Aronson JK. Ferner RE. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ. 2003;327:1222–5
 Classification of adverse drug reactions

Nguyen DV, Vidal C, Chu HC, van Nunen S. Human leukocyte antigen-associated severe cutaneous adverse drug reactions: from bedside to bench and beyond. Asia Pac Allergy. 2019;9(3):e20. Published 2019 May 31.
doi:10.5415/apallergy.2019.9.e20
 Preventing adverse drug reactions
• Epidemiological studies tend to find that between a third and a half of ADRs are
(at least potentially) preventable although preventability is much easier to
diagnose in hindsight
• interventions that reduce the probability of an ADR occurring can be an
important way to reduce the risk of patient harm
• There are two basic steps that can be followed to prevent an ADR occurring:
Identify the subgroup of patients who are likely to be susceptible to the
adverse effect and modify the treatment choice accordingly.
Ensure the treatment plan mitigates any possible adverse effects.

Ferner RE. Aronson JK. Preventability of drug-related harms - part I: a systematic review. Drug Saf. 2010;33:985–94
 Identifying susceptibility
• Knowledge of patient susceptibilities can inform your prescribing decision and
reduce the risk of an ADR
• A patient's medication history will identify any previous ADRs and therefore
preclude re-exposure to the drug
• susceptibility factors such as age, gender, pregnancy status and ethnicity can help
predict the risk of an ADR occurring
National Institute for Health and Care Excellence guidance has suggested that
patients of African or Caribbean descent should be prescribed an angiotensin-
II receptor blocker in favour of an angiotensin converting enzyme (ACE)
inhibitor for hypertension because of the risk of ACE inhibitor-induced
angioedema
Pharmacogenetics is starting to yield more personalised medicine choices by
predicting who is more susceptible to suffer a specific ADR
Pharmacogenetic susceptibility for drug-specific
adverse drug reactions
RISK FACTORS
RISK FACTORS
 RISK FACTORS
HIV/AIDS Patient
 Treatment plan
• Prudent, safe prescribing is key to reducing errors that can contribute to ADRs
Eg.
• Co-prescription of folic acid with methotrexate will reduce the incidence of
adverse effects associated with folate deficiency;
• Monitoring electrolytes and renal function when treating with renally active
drugs or diuretics
• Prudent prescribing may also avoid the use of drugs altogether and the treatment
plan should always consider non-pharmacological or conservative options.

prudent prescribing may also avoid the use of drugs altogether and the treatment plan should always consider non-pharmacological or conservative options.
 Diagnosing adverse drug reactions
• Emulating ‘traditional diseases’ and manifesting in all systems of the body
• Drug-related problems in patients admitted to hospital may present in many
different ways, including weakness or drowsiness, biochemical or haematological
derangements (such as acute kidney injury, electrolyte imbalance or anaemia),
bleeding, gastrointestinal disturbances, hypoglycaemia or healthcare-associated
infections such as Clostridium difficile
• Rarer manifestations – such as drug-induced lupus, fixed drug eruptions, drug-
induced eosinophilia or angioedema – require a level of vigilance and suspicion
on behalf of the clinician who should look very hard to identify a causative agent
 Diagnosing adverse drug reactions
• A comprehensive medication history is fundamental in identifying any possible
connection between a presenting complaint or subsequent finding and an ADR,
as well as preventing future ADRs
• Various criteria can help in attributing causality to a particular drug
Clinical assessment of adverse drug reaction (ADR)
probability

Naranjo CA. Busto U. Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45
Clinical assessment of adverse drug reaction (ADR)
probability

Naranjo CA. Busto U. Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45
Data needed for causality assessment
Data needed for causality assessment
Data needed for causality assessment
Data needed for causality assessment
Data needed for causality assessment
Causality assessment
Causality assessment
Causality assessment
Causality assessment
Causality assessment
Causality assessment
Causality assessment
 Pharmacovigilance
• ‘The science and activities relating to the detection, assessment, understanding
and prevention of adverse events or any other drug-related problem’.

‘the science and activities relating to the detection, assessment, understanding and prevention of adverse events or any other drug-related problem’.
 Managing adverse drug reactions
• Altering a dosage regimen
• Withdrawing a medicine suspected of causing an ADR are common methods of
managing ADRs in practice
• Antidotes for direct oral anticoagulant-induced bleeding

Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016;16(5):481-485. doi:10.7861/clinmedicine.16-5-481
“There are some patients that we cannot
help; there are none whom we cannot
harm.”
Attributed to Arthur L. Bloomfield in BMJ 2004; 329:1-2
ADVERSE EVENTS
 ADR MONITORING IN POST MARKETING - ROLE OF
PHARMACOVIGILANCE

Pharmacovigilance: The science and activities relating

to the detection, assessment, understanding and
prevention of adverse events or any other drug-related
problem
 SIGNIFICIANCE OF PHARMACOVIGILANCE

Adverse drug reaction(ADR)

Effect Medication error

DRUG Drug quality

Thất bại điều trị

“All are dangerous. Only some of them are beneficial”

Nicholas Moore, BMJ; 2005

 Pharmacovigilance and safe drug use

Safe drug use

Drug
quality ADR
Detectio Evalu Understa Preve
n ation nd ntion Medication Promote
error community health

Activities Factors Purposes

 Pharmacovigilance

Drug quality

Spontaneous report

Pharmaco
ADR Medication
vigilance error

ADR Active monitoring

Treatment failure
 HISTORY OF VIETNAM PHARMACOVIGILANCE SYSTEM

1994
Northern 1999 2005
Center Official member of Under
UMC Administration of
Drug
2009
Establishment of
National Center

2011
1998 Establishment of Regional Center
Southern
Center
 VIETNAM PHARMACOVIGILANCE SYSTEM
Path of Report
National DI&ADR Center,
Regional DI & ADR Center
Drug Safety Professional Council

Drug quality
problem ADR Pharmacovigilance
ADRs Causality
Medication Assessme
nt

Report
error

UMC/WHO
Coding database
Drug information
report

Inform
Detection/Prevention
Medical staff, hospitals, Cơ sở dữ liệu
report UMC/WHO
pharmaceutical production and answer
trading units

Inform
 Drug Administration of Vietnam
Administration Decision  Department of medical service administration
THANK YOU