Annals of Medical Research Original Article

DOI: 10.5455/annalsmedres.2019.07.430 2019;26(10):2158-63

Drug-drug interactions in intensive care units and

potential clinical consequences of these interactions
Ersoy Oksuz1, Muhammet Serdar Bugday2, Celaleddin Soyalp3, Erol Karaaslan4, Gokhan Oto5,
Rezzan Temelli Goceroglu5, Ilhami Berber6
1
Malatya Training and Research Hospital, Clinc of Medical Pharmacology, Malatya, Turkey
2
Malatya Training and Research Hospital, Clinc of Urology, Malatya, Turkey
3
Yuzuncu Yil University, Faculty of Medicine, Department of Anesthesia and Reanimation, Van, Turkey
4
Inonu University, Faculty of Medicine, Department of Anesthesia and Reanimation, Malatya, Turkey
5
Yuzuncu Yil University, Faculty of Medicine, Department of Medical Pharmacology, Van, Turkey
6
Malatya Training and Research Hospital, Clinc of Hematology, Malatya, Turkey

Copyright © 2019 by authors and Annals of Medical Research Publishing Inc.

Abstract
Aim: Drug-drug interactions (DDIs) are an important factor that can lead to serious health problems by increasing or decreasing the
effects of drugs. This study aimed to evaluate the frequency of DDIs in the intensive care unit (ICU).
Material and Methods: All patients who were hospitalized for more than 24 h in the ICU of our hospital between January and
September 2018 and received 2 or more medications were included in this retrospective study. Frequency and severity of the DDIs
were detected using the Rx Mediapharma and Lexi-Interact programs.
Results: Of the 972 patients enrolled in the study, 2742 incidences of DDIs were detected in 626 patients (64%). Of the different
drug pairs administered, 422 had DDIs, and 64 of those had 10 or more DDIs, constituting 67% of all of the DDIs. The most common
potential clinical consequences of DDIs were increased risk of bleeding (12.3%), hyperkalemia (8.2%), arrhythmia (7.9%), and CNS
depression (6.6%).
Conclusion: The results indicated that DDIs in the ICU were very common in our hospital. Moreover, these results indicated that
patients should be closely monitored for the prevention of adverse effects, such as electrolyte disturbance, bleeding risk, and
arrhythmia of drugs.

Keywords: Drug-drug interaction; intensive care unit; adverse drug reaction.

INTRODUCTION care services, where the rate of DDIs ranged from 9%–
70%, and 1%–23% of them were shown to cause serious
DDIs are significant medical issue that can change the health problems (2). In another study, the rate of DDIs
effect of drugs, cause life-threatening adverse drug in prescriptions written to outpatients in hospitals was
reactions (ADR), and prolong patient recovery time (1). approximately 27/1000(4). In a different study, in which
DDIs are common in patients receiving a larger number hospitalized patients were investigated, the DDI rate was
of medications, but they can be preventable and easily 1/70 prescriptions (5).
detectable before administration. In addition to a larger
number of medications, the frequency of DDIs changes Patients hospitalized in the intensive care unit (ICU)
according to age, gender, and the individual diseases have more severe diseases, multiple organ failures, and
of the patients (2). DDIs are responsible for 17% all more intensive drug treatments than other hospitalized
of adverse drug reactions and approximately 1% in patients. In addition, these patients have circulatory
hospitalized patients (3). In many studies, DDIs have been disorders and metabolism rate of drugs variety due to
revealed in very common prescriptions at different stages organ failure. Due to these factors, the incidence of DDIs
of health services, such as in a study that examined the in patients in the ICU is higher than in other outpatients
prescriptions of patients who received primary health and inpatients in hospitals (6). In a study conducted in

Received: 24.07.2019 Accepted: 21.08.2019 Available online: 21.10.2019

Corresponding Author: Ersoy Oksuz, Malatya Training and Research Hospital, Clinc of Medical Pharmacology, Malatya, Turkey
E-mail: drugoksuz@hotmail.com

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the ICU, 10% of patients in the ICU were shown to develop Nevertheless, the recommended opinion for 1, 2, and 3,
ADRs due to DDIs (7). In another study, DDIs were found in and C, D, and X are similar in both databases. For example,
3892 of 9644 patients in the ICU (8). Reported that 54% of 1/C: monitor therapy, 2/D: consider therapy modification,
patients hospitalized in the ICU were found to have DDIs 3/X: avoid combination. Therefore, the severity of the DDIs
and the frequency of DDIs increased in direct proportion to was classified in accordance with both database systems.
the length of hospital stay and number of drugs used (9).
Statistical analysis
The aim of this study was to determine the frequency of The statistical package program SPSS 23.0 for Windows
DDIs in patients hospitalized in the ICU and the potential (IBM Corp., Armonk, N.Y., USA) was used to perform the
clinical consequences of these interactions. descriptive statistics analysis of the data. The categorical
variables in the study were indicated by numbers and
MATERIAL and METHODS percentages and the Z-ratio test was used for comparisons
between the two ratios. Statistical significance level
Setting and study population (α) was taken as 5% in the calculations and Minitab
Ethical approval was provided by the Inonu University (Statistical Software for Windows, Ver.17) statistical
Scientific Research and Publication Ethics Committee package program was used for the calculations.
(2018/21-7). This retrospective study was performed in
the ICU of the Malatya Training and Research Hospital, in RESULTS
Turkey. This hospital has 36 beds in ICU unit and there is no
a management system to detect possible DDIs. The data The demographic characteristics of the 972 patients
of 1257 patients who were hospitalized in the ICU between included in the study are shown in Table 1. The number of
January and September 2018 were screened from the
hospital’s database. A total of 972 patients who received Table 1. Characteristics of the study population
2 or more systemic drugs were included in the study. The
exclusion criteria were patients who were below 18 years Total patients (n: 972) n %
of age, stayed for less than 24 h in the ICU, received less Male 505 52
than 2 drugs or did not receive systemic drugs had a very
long stay in the ICU and drug information could not be Female 467 48
correctly detected. The demographic characteristics of Discharge from hospital/transfer to general wards 719 74
the patients, diseases that cause hospitalization, duration
of hospitalization, conditions of death and discharge, Mortality 253 26
medications applied during the duration of hospitalization, Age
and dates and numbers of the drug administration were
recorded by the patient’s epicrisis. >80 278 29
≥50–80 538 55
DDI evaluated
<50 156 16
All the drugs administered to the patient during the DDIs
scan were determined according to the application days Diseases
and the two potential drugs were given to the patient
Respiratory diseases 305 31
at the same time were included in the study however
drugs that were not administered at the same time were CNS diseases 162 17
excluded from the study. The DDIs were evaluated using
Trauma 152 16
databases such as Rx Mediapharma 2018, which is a
patented and widely used drug information system for Cardiovascular diseases 75 8
the detection of DDIs in Turkey, the Lexi-Interact online
Post-op observation 74 8
interactions checker, drug prospectuses, pharmacology
books, and other similar studies in the ICU. Between Other diseases 56 6
which drugs did the interactions occur, and the clinical Intoxication 53 5
consequences, severity, and frequency of the DDIs were
recorded. Frequency of each risk rating category of DDIs Renal diseases 50 5
was calculated by percentage of total number of DDIs Malignity 45 4
[number of each risk rating category DDI / total number
of DDIs × 100]. The clinical severity of DDIs was classified Number of drugs used
as 1, 2, 3 with the Rx and C, D, X risk rating categories in 1–10 438 45
accordance with the Lexi- Interact online database system.
The severity of the DDIs was categorized as 1, 2, and 3, 11–20 408 42
with minor, moderate, and severe in Rx mediapharma. 20> 126 13
However, the severity of DDIs was categorized as C, D,
and X with moderate, major, and severe in Lexi-Interact. CNS, central nervous system

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females and males included in the study was similar DDI frequency
(48%–52%). The patient ages ranged between 18 and 102, Drugs were administered 53,379 times to 972 patients
and most were between 50 and 80 years old (55%). The and the number of DDIs were 2742 (5.1%). The mean
total number of days in the ICU for these patients was DDIs range per patient was 2.8%. DDIs were detected
6722 and the median length of stay in the ICU was 6.9 in 626 patients and the DDIs range in these patients
days. was 4.4%. The number of patients with only 1 instance

Table 2. Main parameters of patients with DDIs

Patient with DDIs No. of ICU days with DDIs

Total patients n: 972 Total n: 6722
Total 64% (626) 80% (5348/6722)
Gender
Male 63% (318/505)a 78% (2838/3658)b
Female 66% (308/467)a 82% (2510/3064)a
Age
>80 67% (187/278)a 83% (1918/2308)a
>50–80 69% (372/538) a
81% (2995/3675)a
≤50 43% (67/156)b 59% (435/739)b
Discharge from hospital 60% (433/719) b
75% (2988/3978)b
Mortality 76% (193/253)a 86% (2360/2744)a
Length of stay in the ICU, days
1 50% (113/226)b 50% (113/224)b

2–5 57% (229/404)b 59% (724/1233)b

>5–10 81% (134/166)a 80% (1019/1268)a

>10 85% (150/176) a
87% (3492/3997)a
Diseases
Respiratory diseases 77% (236/305)a 87% (2345/2690)a
Cardiovascular diseases 75% (56/75) a
87% (609/704)a
CNS diseases 67% (109/162)a 78% (1115/1432)ab
Trauma 58% (88/152)b 85% (661/779)a
Renal diseases 56% (28/50)b 63% (170/272)b
Malignity 56% (25/45) b
67% (76/113)b
Post-op observation 55% (41/74)b 44% (119/272)c
Other diseases 54% (30/56) b
70% (222/319)ab
Intoxication 25% (13/53)c 22% (31/141)d
Number of different drugs used
1–10 40% (176/438)b 36% (414/1142)b
11–20 82% (333/408) a
81% (2187/2712)a
20> 93% (117/126)a 96% (2747/2868)a
a, b, c: Show the difference between categories in the same column for each attribute according to z test.

of DDIs was 163 (17%), with 2–10 instances was 409 DDIs were significantly higher in patients who were older
(65%), and with >10 instances was 54 (6%). DDIs were than 50 years and administered more than 10 drugs and
seen on a total of 5348 days in the ICU (80%). Although hospitalized for more than 5 days than others patients
there was no statistically significant difference between (p<0.05). Diseases with the most DDIs were respiratory
the frequency of DDIs in male and female patients, DDIs diseases, such as chronic obstructive pulmonary disease,
was significantly higher in female patients compared to pneumonia, and cardiovascular disease (CVD) (77% and
hospitalization period (p<0.05). The frequency of DDIs 75%, respectively) and DDIs frequency were significantly
were significantly higher in died patients than patients who higher in these diseases compared to others (p<0.05)
were transferred to other wards (p<0.05). The frequency of (Table 2).

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Table 3. The most common DDIs (n ≥ 10)

Drug A Drug B Clinical consequences n/% Severity-Rx/lexi

NSAID, piracetam, clopidogrel, ASA,
Enoxaparin SSRI
Bleeding risk 263/9.2 1/C

Potassium chloride, ACE, ATII,

Enoxaparin spironolactone
Hyperkalemia 215/7.5 1/C

Furosemide ASA, NSAIDs Effects of furosemide may decrease 168/5.9 1,C

Magnesium sulfate, opioid analgesics, Increased risk of central nervous
Midazolam propofol, levetiracetam system depression
100/3.5 2/C, only opiod D

Furosemide Opioid analgesics Adverse/toxic effect of furosemide may increase 87/3 1/C
Furosemide Propofol, thiopental, amiodarone Hypotension 83/2.9 1/C
Furosemide Aminoglycosides Nephrotoxicity and ototoxicity 69/2.4 2/C
Clopidogrel, diltiazem piracetam,
ASA NSAIDs
Bleeding risk/adverse/toxic effect of ASA may increase 64/2.2 2/C

Methylprednisolone ASA, diltiazem Adverse/toxic effect of methylprednisolone may increase 62/2.2 1/C

Digoxin Furosemide, diltiazem Adverse/toxic effect of digoxin may increase (AV bloc) 57/2 1/C

Methylprednisolone Fluoroquinolones Adverse/toxic effect of fluoroquinolones may increase 56/2 1/C

Fluoroquinolones Domperidone, amiodarone Arrhythmia 53/1.9 1/D,X
Furosemide Insulin Effects of insulin may decrease 45/1.6 1/C
Midazolam Diltiazem, fluconazole Adverse/toxic effect of midazolam may increase 40/1.5 1/C
Pantoprazole Fluconazole, modafinil Adverse/toxic effect of pantoprazole may increase 41/1.4 1/C

Atorvastatin Pantoprazole Adverse/toxic effect of Atorvastatin may increase 34/1.2 3/n.i

Methylprednisolone Phenytoin Effects of Methylprednisolone may decrease 33/1.2 1/D

Noradrenaline β-adrenergic blockers Hypertension 32/1.1 3/n.i
Fluoroquinolones Propofol, metronidazole Arrhythmia 27/0.9 2/B,C
Phenytoin Pantoprazole Effects of phenytoin may decrease 27/0.9 1/n.i
Metoclopramide Opioid analgesics Adverse/toxic effect of metoclopramide may increase 27/0.9 2/C
Midazolam Theophylline Effects of Midazolam may decrease 21/0.7 1/D
Ceftriaxone Calcium gluconate Adverse/toxic effect of ceftriaxone may increase 19/0.6 2/D
Noradrenaline Linezolid Hypertension 17/0.6 1/D

Furosemide ACE inhibitors Hyperkalemia/effect of hypertensive may increase 15/0.5 1/C

ASA ACE inhibitors Nephrotoxicity/effect of antihypertensive may decrease 14/0.5 1/C

Gentamicin Cephalosporins Nephrotoxicity 14/0.5 2/C
ASA Insülin Hypoglycemia 13/0.4 1/C
Domperidone Linezolid Adverse/toxic effect of domperidone may increase 13/0.4 1/C
Furosemide Phenytoin, antipsychotics Effects of furosemide may decrease 12/0.4 1/C
Tramadol Ondansetron Effects of tramadol may decrease 12/0.4 1/C
Midazolam Atorvastatin Adverse/toxic effect of midazolam may increase 11/0.4 2/C
Paracetamol Phenytoin Hepatotoxicity 11/0.4 1/C
Noradrenaline Theophylline Effects of sympathicomimetic effect may increase 11/0.4 2/C
Domperidone Metoclopramide Arrhythmia 11/0.4 1/ni
Digoxin β-adrenergic blockers Bradycardia 10/0.3 1/C
Diltiazem Magnesium sulfate Adverse/toxic effect of magnesium sulfate may increase 10/0.3 1/C

Amiodarone β -adrenergic blockers Bradycardia/ventricular arrhythmia 10/0.3 1/C

Phenytoin Midazolam Effects of midazolam may decrease 10/0.3 1/D

Insulin Fluoroquinolones Hypoglycemia/hyperglycemia 10/0.3 1/C
Total 1827/67
ni, no interaction; NSAIDs, nonsteroidal antiinflamatuary drugs; ASA, acetylsalicylic acid; SSRI, selective serotonin reuptake inhibitor; ACE,
angiotensin converting enzyme inhibitor; ATII, angiotensin receptor blocker

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DDIs type (Table 3). DDIs caused a change in the therapeutic effect
DDIs with 10 or more interactions, classified according of drugs, such as increased adverse or toxic effects, or
to the clinical results, are shown in Table 3. DDIs were decreased therapeutic effects (45.4%). Side effects in the
observed in 422 different drug pairs, and of those, 64 cardiovascular system (CVS) were second (31.5%). This
different drug pairs had 10 or more DDIs, which constituted classification was performed according to the presence
67% of all DDIs. The number of drug pairs showing of a specific clinical result (arrhythmia, hypotension,
interaction only once was 152. The number of level 1 DDIs etc.) after the DDIs (Table 4). Furosemide was the
was 2047 (75%), level 2 was 591 (21%), and level 3 was most common drug to cause DDIs (n: 545), followed by
104 (4%) in accordance with Rx and C 2195 (83%), D 312 enoxaparin sodium (n: 508) and acetyl salicylic acid (ASA)
(12%), and X 94 (3.6%) in accordance with lexi interact (n: 464, respectively) (Table 5).

Table 4. Potential clinical consequences of DDIs

n %
Changes in therapeutic effect of drugs 1246 45.4
Increased risk of side effects/toxicity 717 26.1
Decreased risk of efficacy 529 19.3
CVS side effects 863 31.5
Bleeding risk 350 12.8
Arrhythmia (AV bloc-ventricular arrhythmia torsade de points, prolong QT) 225 8.2
Hypotension 155 5.6

Hypertension 68 2.5

Bradycardia 39 1.4
Increased risk of sympathomimetic effect 26 0.9
Electrolyte disorder 236 8.6
Hyperkalemia 231 8.4
Hypokalemia 5 0.2
CNS side effects 221 8
Increased risk of 189 6.9
CNS depression
Serotonin syndrome 20 0.7
Increased risk of epileptic seizures 8 0.3
Increased risk of anticholinergic effect 4 0.1
Other systems 176 6.4
Nephrotoxicity + rhabdomyolysis 42 1.5
Hypoglycemia 41 1.5

Nephrotoxicity + ototoxicity 36 1.3

Nephrotoxicity 34 1.2
Hepatotoxicity 8 0.3
Ulcerogenic effect 7 0.3

Increased risk of NMB 5 0.2

Rhabdomyolysis 3 0.1

Total 2742 100

NMB, neuromuscular blockade; CVS, cardiovascular system; CNS, central nervous system

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Table 5. Most involved drugs to DDIs which included most patients with this ICU issue in Turkey
(n = 972) and the DDI proportion, was determined to be
n
higher than the majority (64%) of studies, both performed
Furosemide 545 in different countries and those in Turkey. It was evaluated
Enoxaparin 508 that the DDIs were higher in our study than in the other
Acetylsalicylic acid 464 studies, because of the different types of drugs used and
the ICU patient conditions, such as age, gender, type of
Fluoroquinolones 238
disease, and the presence of a concomitant disease.
Midazolam 228
The incidence of DDIs was found to increase with an
Diltiazem 141
increase in the number of drugs administered and the
Methylprednisolone 140
length of hospital stay (1, 10). Our results corresponded to
Amiodarone 120 these studies, where the rate of DDIs was 40% in patients
Phenytoin 117 treated with 1–10 drugs, but the rate in patients who were
Metoclopramide 99 administered over 20 drugs was 93% (p<0.05). Again, once
Domperidone 92 the number of hospitalization days was evaluated, the rate
of DDIs in patients hospitalized for a day was 50%, while in
Noradrenaline, adrenaline 75
patients hospitalized for more than 10 days, this rate was
Atorvastatin 74 85% (p<0.05). In addition to the number of medications
The number of interactions between drugs was calculated by including and the duration of hospitalization, the prevalence of DDIs
the number of interactions with each other. in patients increases depending on their age and type
DISCUSSION of disease (3). For example, in a study investigating the
frequency of DDIs in hospitalized patients, the prevalence
The results of our study indicated that the number of of DDIs in patients over 75 years of age was higher than
patients with DDIs in our hospital was very high (64%). patients within a low age group (14). In a study conducted
Once the length of patient hospitalization was evaluated, on outpatient geriatric patients, 50% of patients had DDIs
the frequency of DDIs was even higher (80%), where 25%
and approximately 1/4 had ADRs due to DDIs. In our study,
of these DDIs were interactions at the moderate-severe
the frequency of DDIs was higher in patients over 50 years
level. The most common interactions were with the CVS,
antibiotics, and central nervous system (CNS). The most of age similar to these studies (p<0.05). However, there
common clinical results of the DDIs were increased risk of was no significant difference in the frequency of DDIs in
bleeding (12.3%), hyperkalemia (8.2%), arrhythmia (7.9%), patients over 80 years of age who were expecting greater
and CNS depression (6.6%). frequency of DDIs and between 50 and 80 years of age.
This condition may be caused by existing and comorbid
DDIs are quite common in hospitalized patients and they diseases of individuals over 80 years of age. Many studies
cause a significant proportion of ADRs. However, they are have indicated that DDIs are more common in individuals
more common in patients in various ICU units, such as with CVS and CNS diseases (14, 15). In our study, although
coronary, cardiovascular, and reanimation, which should DDIs were quite high in these 2 disease groups (CVD 75%,
be followed closely and may lead to more adverse events. CNS 69%), they were most commonly found in individuals
However, the frequency of DDIs varies in many studies with lung disease (77%, p<0.05). However, it should be
conducted in different countries in the ICU. For example, a considered that the frequency of DDIs among the disease
study conducted in Brazil indicated that 72.5% of patients groups, the severity of the disease, the age, and the
in the ICU had DDIs (10). In a study conducted in the presence of an accompanying disease can change. In our
Netherlands, this rate was 40% (8). In a US study, similarly, study, the DDIs difference seen among the disease groups
the rate of DDIs was 46.3% (11). In another study by the may have been caused by these reasons. However, there
same authors, the cardiac and cardio-thoracic ICU results is a distinct coronary ICU in our hospital, where cases
indicated that 56% of the patients had DDIs (12). As far of cardiac origin are located; therefore, it is thought that
as we have investigated, there have been 2 studies on this ICU may have caused by low number of results with
DDIs in Turkey. The first was the study of the interaction cardiac origin. Another important finding in our study was
between antibiotics and other drugs in the 1-day patient that the frequency of DDIs in patients who died was much
stay of 5 different hospitals. This study included 427 higher than in patients who were discharged (76%, 60%,
patients (number of patients in the ICU: 108) and the DDI respectively p<0.05). The intense use of medications may
rate was 26.4% (13). The second study was a single- have contributed to the excess of DDIs in these patients,
center perspective study in which 101 patients were due to factors such as the severity of the disease in
included in the ICU and the DDI rate for all of the drugs individuals, presence of co-morbid disease, and desire to
administered to patients was investigated. In that study, rapidly correct the age and general condition. In this case,
DDIs were detected in 45.5% of patients (1). Our study, it is important to make a more careful evaluation in terms

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of the DDIs risk in these patients, before the administration of hospitals in Turkey, it is important to determine that
of ADRs, because the occurrence of ADRs due to DDIs will the majority of the drugs used in ICU patients are similar
worsen the course of the current disease or the general drugs such as furosemide, enoxaparin and ASA. The
condition of the patients. results of our study also indicated that anticoagulant
agents, such as enoxaparin, are routinely used to prevent
Due to the differences in diseases in individuals, there deep vein thrombosis in patients in the ICU, and that such
was a change in the drugs that caused DDIs among the patients should be closely monitored for ADR prevention,
general services of hospitals and the ICU or outpatients. especially for the risk of bleeding and potassium elevation.
For example, in a study investigating the frequency of DDIs Again, because of the widespread use of drugs such as
in hospitalized patients, it was reported that there was an midazolam, it is important to closely monitor patients in
interaction between angiotensin converting enzyme (ACE) the ICU in terms of the prevention of ADR, for such things
inhibitors and diuretics and renin-angiotensin system as arrhythmia with pulmonary disease, CNS depression
(RAS) inhibitors and potassium (16). In another study and pneumonia, and especially cardiac diseases such as
performed in inpatients, the interaction between aspirin arrhythmia.
and warfarin, digoxin and furosemide was the most
common (14). In a study of outpatients, it was found that There were differences between the Rx Mediapharma and
DDIs were the most common with antiparkinsonian drugs lexi programs in terms of the presence of DDIs in both
and dopamine receptor antagonists (4). In another study, programs. For example, in level 1, the number of DDIs in Rx
in which ambulatory patients were examined, diuretics, mediapharma was 2047 (75%), in level 2 it was 591 (21%),
nonsteroidal antiinflammatory drugs (NSAIDs), and ACE and in level 3 it was 104 (4%), whereas in the lexi program,
inhibitors were found to be drugs with DDIs (17). In this it corresponded to C 2195 (83%), D 312 (12%), and X 94
sense, drugs seen with DDIs in ICU patients differ slightly. (3.6%). Of the DDIs, 36 were minor (B) and no was action
For instance, coronary ICU inpatients were most commonly needed (1.4%). With some drugs, such as atorvastatin/
found to have DDIs with anticoagulants or antiplatelet pantoprazole and domperidone/methochlorpramide, the
agents, aspirin, and heparin (12). The same researchers, lexi program did not show DDIs. However, other studies
in a study of ICU patients with DDIs, found insulin and on this issue and drug prospectuses were found to have
beta-blockade and phenytoin and dexamethasone to a potential interaction between these drugs (12). Another
be the second most common interactions, while in the important aspect of our study was the evaluation of both
coronary ICU, anticoagulant or antiplatelet drugs were programs and the detection of significant differences in
found to be among the most common (11,18). In another the severity of DDIs and the comparison of DDIs in both
study conducted on ICU patients, similar to the above programs. Therefore, the use of different programs when
study, it was found that the interactions between insulin investigating DDIs and knowledge of the drug’s properties
and beta blockers were the highest DDIs and the second may be more useful for preventing possible DDIs. In
most frequent interaction was between midazolam addition to the programs in which DDIs are identified, the
and CYP3A4 inhibitors (9). A study performed in Turkey participation of medical pharmacist physicians in patient
indicated that the most common DDIs in ICU patients was visits, especially in units such as ICU and evaluation of
between methylprednisolone and other drugs, while the drugs by these experts and giving information to other
second was among the CVS drug groups, such as digoxin, physicians in this sense is another important aspect for
diltiazem, and furosemide (1). In our study, the most preventing DDIs.
common drugs in DDIs were anticoagulants, antiplatelets,
CONCLUSION
and CVS drugs, such as enoxaparin, ASA, and furosemide.
DDIs involving furosemide were found 545 times with 18 The results of our study indicated that DDIs in the ICU
different drugs, those involving enoxaparin were found were very common in our hospital and the frequency of
508 times with 13 different drugs, and those involving ASA DDIs increased directly proportionally to the duration of
were found 464 times with 18 different drugs. Again, DDIs hospitalization, age, and number of drugs used. Moreover,
involving diltiazem, methylprednisolone, and midazolam these results indicated that patients should be closely
were quite high. Fluoroquinolone group antibiotics, such monitored for the prevention of adverse effects, such as
as ciprofloxacin, moxifloxacin, and levofloxacin were the
electrolyte disturbance, bleeding risk, arrhythmia, because
most common antibiotics to cause DDIs. Once the DDI
the effects of the drugs diminished, and to monitor
results were classified according to the clinical events,
the interaction between enoxaparin and ASA, clopidogrel, the drug orders or to use a variety of software. In our
NSAIDs, etc., was the most common cause of bleeding study, the possible clinical consequences of DDIs were
(9.2%). Moreover, second frequently there were DDIs evaluated. However, determining the frequency of clinical
(7.5%) that can cause hyperkalemia between enoxaparin consequences that may result from potential DDIs is a
and ACE inhibitors, potassium drugs vs. these results more important finding for the evaluation of DDIs. In this
indicated that although there were some differences, the sense, new prospective studies are needed to determine
drugs that caused DDIs in our hospital ICU were similar DDIs and frequency of ADRs which resulting from DDIs.
to the drugs studied in other countries. Our study, as Competing interests: The authors declare that they have no competing
well as being the most patient study of the involvement interest.

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Financial Disclosure: There are no financial supports. 8. Askari M, Eslami S, Louws M, et al. Frequency and nature
Ethical approval: Ethical approval was provided by Ethics Committee. of drug-drug interactions in the intensive care unit
Pharmacoepidemiol. Drug Saf 2013;22:430-7.
Ersoy Oksuz ORCID: 0000-0002-8088-1009
9. Uijtendaal EV, van Harssel LL, Hugenholtz GW, et al.Analysis
Muhammet Serdar Bugday ORCID: 0000-0002-3745-1302
Celaleddin Soyalp ORCID: 0000-0002-2687-5329
of potential drug-drug interactions in medical intensive care
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