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Objective: To evaluate incidence, severity and types of drug-drug interactions
and drug induced abnormalities in hospitalized patients.
Material
and methods: A prospective observational study was
carried out in In-patient department of surgical and medical department in
private hospital. Study conducted after the approval of Ethics committee. Data
were collected for 6 months and drug interactions were identified using
standard references. Drug induced abnormalities were observed from patients
file.
Results: Total 201 cases collected within 6 months and mean age was 62.5 ± 17.3
years. Most of patients are in age between 61 and 80 years (4.47%) The average
incidence rate of DDIs was 66.6%. The most frequently prescribed drug in was
aceclofenac (2.3%) and aspirin (78.33%) in surgical and medical department,
respectively. The most common DDI was reported between clopidogrel and aspirin
(67%). Mechanism of drug-drug interaction was pharmacokinetic (44%) and
pharmacokinetic and pharmacodynamic (71.4%) in medical and surgical department.
In medical department, the minor drug interaction was higher (40%) and in
surgical department, significant and minor drug interactions were at 61%. Out
of 201 cases, 16 cases (7.96%) showed drug induced abnormalities. Most of
patients are in age between 61 and 80 years (4.47%).
Conclusion: The
incidence rate of DDIs was in the range of 64-70%. The majority of DDI were
minor type with no clinical significance. Total 16 cases out of 201 cases
showed drug induced abnormalities.
Keywords:
Drug-drug interaction, Drug induced
abnormalities, Clopidogrel, Aspirin
INTRODUCTION
A drug interaction occurs when the effects of
one drug (the object drug) are altered (increased or decreased) by the effects
of another drug (the precipitant drug) [1]. Drug-drug interaction can increase
hospitalization, increased length of hospital stay, morbidity, mortality and
increased financial costs [1].
There are three types of drug interactions:
pharmacodynamic, pharmacokinetic and pharmaceutical. Pharmacodynamic
interactions usually result from combining two drugs with similar mechanisms of
action and pharmacokinetic occurs due to effect of one drug altering the effect
of another drug by alteration of absorption, distribution, metabolism and
excretion [1]. A pharmacokinetic interaction takes place when a drug
alters the absorption, distribution, metabolism and/or excretion of another
drug. Pharmacokinetic interactions via metabolic effects most often occur via
drug interactions with cytochrome P450 enzymes [1].
In 2004 in the United States, more than 3500
drugs were prescribed and found that more than 81% of persons in a given week
at least one medication and 25% take at least five such medications so
obviously, the potential for an interaction between two or more agents is large
[2]. The Boston collaborative drug surveillance program reported 83,200 drug
exposures in almost 10,000 patients and shown 3,600 adverse drug reactions, of
which 6.5% was resulted from drug interaction [2].
A toxic reaction to or morbid condition
resulting from the administration of a drug is called drug induced
abnormalities [3]. In 1993, the incidence rate of drug
related hospital admissions was reported to range from 0.2% to 21.7%, with the
median rate of drug related hospitalization at 4.9% [4]. The factors that
affect the drug induced abnormalities are pharmacokinetic, pharmacodynamic,
co-morbidities, physiological condition, life style factors, drug-drug
interaction and genetic variabilities [3].
In developing countries, very few
organizations look after the problems related to drug interactions and its harm
to patients and safety monitoring. The Uppsala Monitoring Centre is the one of
the reference for providing information on drug interaction and also concerned
on safety monitoring of medicinal product. In India, very limited activities
are focusing on such type of studies. Therefore, the present study was planned
to identify drug interactions and drug induced abnormalities in hospitalized
patients.
METHODOLOGY
A prospective observational study was carried
out for a period of 6 months (15th July 2014 to 15th
January 2015) at private hospital in western part of Gujarat. The study was
conducted after approval taken from Human Ethics Committee. Prescriptions from
surgical and medical ward of Inpatient department were selected and considered
for data collection. Patients data was collected for 3 days of hospitalization
or till discharged, whichever is earlier. Written prescriptions were evaluated
for drug-drug interaction with the help of Medscape multidrug interaction
software and Stockley’s drug interaction checker [4,5]. On the other hand,
reported laboratory data, medication history, past history, co-morbidities of
patients were additional evaluated for drug induced abnormalities. After
collection of data, the result was prepared by using MS-Excel. Data are expressed
as percentage. Descriptive statistic analysis was used to present the data
results.
RESULTS
Demographical
characteristics
Out of 201 cases, 100 cases were taken from
medical department and 101 cases from surgical department during the time
period. For the ease of analysis, two departments were separately analyzed.
Medical department
The incidence rate of DDIs in medical department
was found to be 64%. The mean age of 55.23 ± 18 years was found including 54%
males and 46% females. The most common presenting complains was arthritis and
42.5% DDIs were observed. Hypertension (32%) was found as the most common
co-morbidity among the group of patients.
Inter-day incidence of DDIs was observed
whereas, high number of prescriptions (116) showed DDIs on 2nd day
of hospitalization as compared to the day of hospitalization. On the 3rd day
DDIs ratio was gradually decreased.
Out of total cases, 27% cases showed serious
DDIs followed by 39% significant and 40% minor type.
Surgical
department
The incidence rate of DDIs in medical
department was found to be 70%. The mean age of 59.73 ± 17.83 years was found
in all together in 29.6% males and 70.4% females. Majority of the patients
(56%) were above the age 61 years. The most common presenting complains was
knee joint pain observed.
Total 1523 drugs were prescribed to surgical
ward included highest prescribing of antibiotics 97 (97.6%). Total 70 cases out
of 100 showed potential DDIs. Total 13 (18.57%) prescriptions showed
pharmacokinetic (PK) type, 7 (10%) prescriptions showed pharmacodynamics (PD)
type of DDIs, while, 50 (71.42%) prescriptions showed both PK and PD types.
Metabolism and excretion type of DDIs were common in surgical department,
examples includes sulfamethoxazole with losartan (10%), ascorbic acid with aspirin
(25%) and furosemide with folic acid (10 %). Aceclofenac with diclofenac is the
DDI observed with pharmacodynamic.
Out of total cases, 34 cases showed serious
DDIs followed by 61cases of significant and 61 minor type.
Day wise incidence of DDIs was compared and
it showed high number (n=239) prescriptions with DDIs on 2nd day of
hospitalization as compared to the day of hospitalization. On the 3rd
day DDIs ratio is gradually decreased (n=109).
Drug induced abnormalities
DISCUSSION
Our study aim was to analyze prescription for
possible drug-drug interaction in medical and surgical ward of Inpatient
department. Total 470 prescriptions were reviewed from 201 patients including
both medical and surgical Inpatient department of the hospital. The mean age
was found to be 62.5 ± 17.3 years. Out of 201 cases, 100 cases were taken from
medical department. In our study, out of 100 patients, mean age was 55.7 ± 18
years. The majority of patients in the present study belong to age group of 61-80
years. The incidence rate of DDIs in medical department was found to be 64%. In
another study by Patel et al. [2], out of 350 prescriptions were taken from
medical department; mean age was 52.45 ± 14.49 years. The incidence rate of
drug interactions was found to be 83.42%. [2] In our study, sixty four (64%)
prescriptions had the potential for drug interaction out of 100 prescriptions.
Our study findings are similar with previous reported study.
In our present study, out of 201
prescriptions, 134 prescriptions show drug-drug interaction. Out of 134
prescriptions, 111 (82.83%) prescriptions showed pharmacokinetic drug
interaction and 23 (17.16%) prescriptions showed pharmacodynamic drug
interaction. The study carried out by Patel et al. [2], the pharmacodynamic
drug interaction was 68.92% and 26.76% prescriptions had shown pharmacokinetic
drug interaction, which differs from us.
In our study, total 43 (67%) cases were found
with aspirin and clopidogrel combination and cause serious problem and need
monitoring. Reported data says that, aspirin and clopidogrel resistance are
emerging clinical entities with potentially severe consequences such as recurrent
myocardial infarction, stroke, or death [6]. Additionally we found that four
prescriptions with nine types of DDIs and on contrary, 36 prescriptions showed
no drug interactions. Total 64 cases showed DDIs, out of this, 48 (44%) and 39 (35%)
cases showed pharmacokinetics (PK) and pharmacodynamic (PD) type of DDIs
respectively. Metabolism (28%) was the most common type of PK interaction
followed by absorption and excretion. The most frequently occurring drug
interaction at metabolism was between barbiturates and pantoprazole (13, 50%)
in the present study. Study by Shetty et al. [7] reported majority of the drug
interactions were pharmacokinetic in nature.
Out of total cases, 27% cases showed serious
DDIs followed by 39% significant and 40 % minor type in present study whereas
the study carried out by Patel et al.
[2], out of 500 prescriptions, only 3.67% showed serious drug interaction,
73.37% significant drug interaction and 22.94% minor drug interactions.
Interday incidence of DDIs was observed in
medical ward where, high number of prescriptions (116) showed DDIs on 2nd
day of hospitalization as compared to the day of hospitalization. On the 3rd
day DDIs ratio was gradually decreased. Study done by Gupta et al. [8] reported
that as stay prolonged the rate of DDIs occurrences increased.
In the surgical
department, the
incidence rate of DDIs in medical department was found to be 70%. The mean age
of 59.73 ± 17.83 years was found in all together in 29.6% males and 70.4%
females. Majority of the patients (56%) were above the age 61 years. The most
common presenting complains was knee joint pain observed. Out of 101
prescriptions of surgical department, 70 (70.1%) showed drug interaction. While
in other study carried out by Patel et al. [2] in India, 50 prescriptions were
from surgical department. 40 prescriptions shown pharmacokinetic interaction
and 27 had pharmacodynamic drug interaction [2].
In this study, highest prescribing of
antibiotics 97 (97.6%) was found in surgical department. Total 70 cases out of
100 showed potential DDIs. Total 13 (18.57%) prescriptions showed
pharmacokinetic (PK) type, 7 (10%) prescriptions showed pharmacodynamics (PD)
type of DDIs, while, 50 (71.42%) prescriptions showed both PK and PD types.
Metabolism and Excretion type of DDIs were common in surgical department,
examples includes sulfamethoxazole with losartan (10%), Ascorbic acid with
aspirin (25%) and Furosemide with folic acid (10%). Aceclofenac with diclofenac
is the DDI observed with pharmacodynamic.
Out of total cases, 34 cases showed serious
DDIs followed by 61cases of significant and 61 minor type. This was consistent
with other studies in which severity range was from 64%-70.4% in moderate
category [9-11]. Additional day wise incidence of DDIs was compared and it showed
high number (n=239) prescriptions with DDIs on 2nd day of
hospitalization as compared to the day of hospitalization. On the 3rd
day DDIs ratio is gradually decreased (n=109).
In our study, the digoxin induced
hyperkalemia occurred in 1 case out of 201 prescriptions. The study carried out
by Khanagavi et al. [12] in USA, it was studied that out of 15,608
hospitalizations, the digoxin induced hyperkalemia was in 408 patients. In our
study, drug used like pantoprazole,
metoprolol and antibiotic - Sublactum β-lactamase caused raised SGPT level.
Whereas drugs like furosemide and lactulose caused fluctuation of sodium level.
Additionally Aspirin showed case of GI bleeding in the present study.
Gastrointestinal bleeding due to NSAID, acetylsalicylic acid and warfarin were
the most common DIDs reported by Brvar et al. [13].
CONCLUSION
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5. Baxter
K (2000) Stockley’s drug interaction checker. 8th Edn,
Pharmaceutical press.
6. Wang
TH, Bhatt DL, Topol EJ (2006) Aspirin and clopidogrel resistance: An emerging
clinical entity. Eur Heart J 27: 647-654.
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V, Chowta MN, Chowta NK, Shenoy A, Kamath A, et al. (2018) Evaluation of
potential drug-drug interactions with medications prescribed to geriatric
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M, Chincholkar AS, Wagh RJ, Maheshwari N, Siddiqui W (2016) A study of
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GW, Bleich A, Chiamulera P, Sanches AC, Schneider DS, et al. (2009) Frequency
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10. Secoli
SR, Figueras A, Lebrao ML, Lima FD, Santos JL (2010) Risk of potential
drug-drug interactions among Brazilian elderly: A population based, cross
sectional study. Drugs Aging 27: 759-770.
11. Teixeira
JV, Crozatti MT, Santos CA, Lieber NS (2012) Potential drug-drug interactions
in prescriptions to patients over 45 years of age in primary care, southern
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12. Khanagavi J, Gupta T, Aronow WS, Shah T, Garg J, et al. (2014) Hyperkalemia among hospitalized patients and association between duration of hyperkalemia and outcomes. Arch Med Sci 10: 251-257.
13. Brvar M, Fokter N, Bunc M, Mozina M (2009) The frequency of adverse drug reaction related admissions according to method of detection, admission urgency and medical department specialty. BMC Clin Pharmacol 9: 8.
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