Introduction
The World Health Organization (WHO) defines an adverse
drug reaction (ADR) as "a response to a medicine which is noxious and
unintended, and which occurs at doses normally used in man". The adverse effect is Òany
undesirable or unintended consequence of drug administrationÓ; and ÒADR
requires treatment or decrease in dose or indicates caution in the future use
of the same drugÓ (Tripathi
et al, 2013). ADRs are encountered daily in an outpatient and in-patient
hospital setting. Hospital admissions of 3 to 6 % of all admissions are due to
ADR; and ADRs can occur in 10 to 15 % of hospitalized patients, which can
result in morbidity, prolonged hospitalization, and risk of mortality (Thong B et al., 2011). The
prevalence of ADR is on the rise due to the increasing number of drugs being
marketed on a large scale, increasing population, and the trend of polypharmacy
being practiced in most health care institutions. Barr mentioned that "One
of the great hazards in the use of potent drugs is their inherent toxicity and
the dangers of the drug appear to be greater now than ever before" (Wiffen P et al., 2002). With the
rapid availability and use of medications in the last few decades, the number
of adverse events associated with drugs is on the rise.
ADR can significantly increase mortality and
morbidity, affecting the quality of life and prolonging the hospital stay. ADRs
are also the reason for 3-6 % of all hospital admission worldwide. The United
Kingdom (UK) and Europe see an annual hospital admission of 14,60,000 due to
ADRs and the United States of America has about half of those in Europe and the
UK (Wiffen P et al., 2002). The necessity of reporting ADR is
important for the benefit of the patient and the health care delivery system.
The actual incidence of ADRs can be even more as the reported cases are just
the tip of the iceberg. It is thus imperative to give attention to quickly
identifying the ADRs, the population at risk, and the drugs commonly involved.
The aim of our study is first, to review types of ADRs
related to drugs used in a tertiary care hospital in Jorhat, Assam, India, and
second, to analyze the ADRs for causality, severity, and preventability.
Methods
The study was carried out in a tertiary care hospital
in Jorhat after getting approval from Institutional Ethical Committee, for six
months from 1-June-2015 to 30-Nov-2015.
The study population included patients reporting the
adverse drug event during the study period in the hospital outpatient
department (OPD) or Indoor patient department (IPD). Information on accidental
intake, self-harm with drugs, and other medication errors were excluded from
the study.
Study wards and OPDs were visited daily and the ADR
details were collected from the reporting physician, patient, or the attendant
in an ADR reporting form available at Central Drugs Standard Control
Organization (CDSCO), Government of India website (CDSCO, 2019). In addition, health staff was informed
to inform directly, either in person or through ADR forms that were made
available in the OPDs and wards. The ADR reporting form could be filled in by a
designated reporter with the required information (suspected drug, suspected
reactions, identifiable patient, and reporter) to make it a valid report.
Suspected ADRs were reviewed for casualty according to
the Naranjo probability scale wherever applicable where- Definite= Score equal
to or more than 9, Probable = 5-8, Possible = 1-4, and Doubtful= 0 (Naranjo et al, 1981). The
severity of the adverse reactions was assessed using Modified Hartwig and Siegel ADR Severity Assessment Scale - which
classifies ADR into mild, moderate, and severe (Srinivasan et al., 2011). And lastly, the
preventability assessment was done by using Schumock
and Thornton scale. It classifies ADRs into definitely preventable, probably
preventable, and not preventable (Schumock et al., 1992). According to this scale, the
ADRs were "definitely preventable" if the answer was "yes"
to one or more questions in section A. If answers were all negative
then we proceeded to section B. ADRs were "probably preventable" if
the answer was "yes" to one or more questions in section B. If
answers were all negative then we proceeded to section
C. In Section C the ADRs was non-preventable.
Statistical analysis was done using Microsoft excel.
We calculated the mean, median, and frequencies of multiple risk factors like
age group, gender, drug group, causative drugs. Comparison between groups was
done using the Chi-square statistical test for assessing significance. The
p-value < 0.05 was taken as significant.
Results
Forty-two cases of ADRs were detected, with 9
different types of ADRs; with incidence higher in males (61.9 %) than females
(38.1 %). Outpatients subjects were 37 (88.1 %), and 5 (11.9 %) were
inpatients. The proportion of patients aged < 18, 18-65 and > 65 years
were 11.9 %, 85.7 %, and 2.4 %, respectively.
Commonly reported ADRs were tremors with an incidence
of (33.3 %), followed by a rash, dizziness, facial and pedal edema (Fig. 1). In
our study, the drug with maximum ADRs was haloperidol followed by amoxicillin
and diclofenac. No history of previous drug history and systemic illness was
present.
The casualty, severity, and preventability are
mentioned below:
Table 1:
Casualty of ADRs
|
Types
|
Number of ADRs
|
Percentage (%)
|
|
Possible
|
36
|
85.7
|
|
Probable
|
4
|
9.5
|
|
Definite
|
2
|
4.8
|
|
Total
|
42
|
100
|
Table 2:
Severity assessment of ADRs
|
Category
|
Number of ADRs
|
Percentage (%)
|
|
Mild
|
16
|
38.1
|
|
Moderate
|
26
|
61.9
|
|
Severe
|
0
|
0
|
|
Total
|
42
|
100
|
Table 3:
Preventability assessment of ADRs
|
Types
|
Number of ADRs
|
Percentage (%)
|
|
Definitely preventable
|
2
|
4.8
|
|
Probably preventable
|
6
|
14.3
|
|
Not preventable
|
34
|
80.9
|
|
Total
|
42
|
100
|
To find out the significant risk factors Chi-square
test was applied. Multiple drug therapy and history of allergies had a
significant p-value when compared with the severity of the reaction. The
study- groups were divided into 2 as shown below:
Table 4:
Comparison between mild & moderate groups
|
Category
|
Mild
|
Moderate
|
p-value
|
|
Age
|
29.5
|
29.9
|
0.80
|
|
History of previous allergies
|
9
|
33
|
<0.05
|
|
Multiple drugs
|
17
|
25
|
<0.05
|
Most of the ADRs were assessed as possible (85.7 %),
severity was moderate (61.9 %) in the majority of the cases, and
non-preventable (80.9 %) in most of the cases.
The age group of the patients with ADR did not show
any significant difference. However, a significant (p < 0.05) difference was
present between the use of multiple drugs and history of previous allergies in
between the severity categories of ADRs.
Discussion
The Lazarou review has been
criticized recently on several points, including heterogeneity of studies and
the value of extrapolating small numbers of fatal ADRs to a whole population (Lazarou et al, 1998). Nonetheless,
there are consistent patterns of ADRs that are significant to individuals and
institutions.
ADRs were highly distributed in males (Male: Female
ratio is 13:8). It contrasts a few pieces of literature which mention that ADR
is more common in females. There was no significant difference between the age
groups of the patients having ADRs. This is in contrast to studies that suggest
the very young and very old populations are more susceptible to having more
ADRs, reflecting the age-related difference in body composition and activity of
metabolic pathways. If the suspected drugs are analyzed as per the ATC
(Anatomical Therapeutic Chemical) classification, the drugs for nervous system
disorders are the most common causative drugs (psycholeptics,
anti-depressants) of ADRs. Our study is in accordance with the study of Pourpak et. al., where the risk factors, including multiple
concomitant drug intake, history of allergies, are associated with the severity
level of the ADRs (Pourpak
et al., 2008).
Most of the ADRs were considered possible where the
event could be attributed to the offending drugs with a plausible onset latency
and other factors like the absence of a confounding factor or a positive dechallenge. The majority of the ADRs were moderately
severe as accessed by the Modified Hartwig's Severity
Assessment Scale. In subjects with a history of allergy and multiple
concomitant drugs,
developed a greater number of moderate level severity reactions
which was statistically significant. There were ~ 5-15 % preventable ADRs which
have a previous history of similar reactions and a lack of awareness had led to
its recurrence. Prevention of these reactions could have been made possible by
educating the patient regarding the drug and the symptoms of associated ADRs.
Our study has its limitations considering small sample
size and a shorter timeline. Hence these results cannot be extrapolated to the
rest of the population. A re-challenge test was not conducted due to patient
concerns and ethical issues. Allergic patch test was not done and missing
information in ADR reporting forms were other constraints faced during the
study. There are variations when compared with other study populations.
Conclusions
The result of our study indicates that the patient
taking such drugs should be closely monitored. The present study will give an
opportunity to achieve the aim using preparing and collecting useful
information on ADRs. A database built upon the basis of such studies conducted
across multiple centers can go a long way in avoiding clinically significant
harmful consequences.
Acknowledgment
The authors acknowledge the contribution of the AMC
coordinator of JMCH, Dr. Swapnanil Gohain, Assistant professor, Pharmacology, JMC.
Conflict of
interest
The authors declare no conflict of interest.
Reference
Cdsco.gov.in. 2019[cited 20 August 2019]. Available
from: https:// cdsco.gov.in /opencms
/export/sites/CDSCO_WEB/Pdf-documents/ Consumer_Section_PDFs
/ADRRF_2. pdf. Tripathi K. Essentials of medical pharmacology. 7th ed. New
Delhi: Jaypee Brothers Medical Publishers (P) Ltd;
2013.
Lazarou, J., Pomeranz, B. H., & Corey, P. N. (1998). Incidence of
adverse drug reactions in hospitalized patients: a meta-analysis of prospective
studies. JAMA, 279(15), 1200Ð1205.
Naranjo, C. A., Busto, U., Sellers, E. M., Sandor, P., Ruiz, I.,
Roberts, E. A., Janecek, E., Domecq, C., &
Greenblatt, D. J. (1981). A method for estimating the probability of adverse
drug reactions. Clinical pharmacology and therapeutics, 30(2),
239Ð245.
Pourpak, Z., Fazlollahi, M. R., & Fattahi,
F. (2008). Understanding adverse drug reactions and drug allergies: principles,
diagnosis and treatment aspects. Recent patents on inflammation &
allergy drug discovery, 2(1), 24Ð46.
Srinivasan, R., and Ramya,
G. (2011). Adverse drug reaction-causality assessment. IJRPC, 1(3), 606-12.
Schumock, G. T., &
Thornton, J. P. (1992). Focusing on the preventability of adverse drug
reactions. Hospital pharmacy, 27(6), 538.
Thong, B. Y., & Tan, T. C. (2011). Epidemiology and risk factors for
drug allergy. British journal of clinical pharmacology, 71(5),
684Ð700.
Tripathi, K. (2013).
Essentials of medical pharmacology. 7th ed. New Delhi: Jaypee
Brothers Medical Publishers (P) Ltd.
Wiffen. P., Gill, M.,
Edwards, J., Moore, A. (2002). Adverse
drug reactions in hospital patients. A systematic review of the prospective and
retrospective studies. Bandolier Extra. Evidence
based health care, June 2002, 01-15.
