Jurnal Ilmu Farmasi dan Farmasi Klinik
(Journal of Pharmaceutical Science and Clinical Pharmacy)
ISSN 1693-7899 (print) - 2716-3814 (online)
DOI: 10.31942/jiffk.v21i1.9529

Identification of Potential Drug Interactions of Patients with
Chronic Kidney Disease Based on Lexicomp® Application
Okta Muthia Sari*, Putri Nur Azizah, Aditya Maulana Perdana Putra
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Lambung Mangkurat University,
Banjarmasin, South Kalimantan, Indonesia

ABSTRACT: One of the factors that cause chronic kidney disease is comorbid diseases.
Comorbidities can lead to polypharmacy, which can increase the potential for drug
interactions. Potential drug interactions, if not addressed, can increase the incidence of
morbidity and mortality. The purpose of the study was to identify potential drug interactions
with drugs for patients with chronic kidney disease using the Lexicomp® application in terms
of risk level, severity, and recommendations for the treatment of drug interactions. The study
was conducted at Ansari Saleh Hospital, Banjarmasin, from January to February 2024. The
study sample consisted of 58 patients. Data were analyzed using the Lexicomp® application.
The results showed that 56.90% of the patients had potential drug interactions, with 175 cases
of potential drug interactions in 53 drug combinations. The percentage of potential drug
interactions based on risk level was 31.43% (category B), 61.71% (category C), 4% (category
D), and 2.86% (category X). The percentage of potential drug interactions according to severity
was 33.71% (minor), 62.29% (moderate), and 4% (major). Treatment recommendations for
drug interactions with drugs include not need for action, monitoring therapy, and dose
adjustment. Potential drug interactions with drugs for patients with chronic kidney disease
using the Lexicomp® application in terms of the majority of risk levels in category C, the
severity of most moderate categories, and recommendations for handling drug interactions for
the majority need to monitor therapy and dose adjustments. Chronic kidney disease patients
have the potential to experience moderate drug-drug interactions of the category, with
treatment recommendations that require therapeutic monitoring.
Keywords: handling recommendations; risk of drug interactions; severity of drug interactions

*Corresponding author:
Name : Okta Muthia Sari
Email : okta.sari@ulm.ac.id
Addres : Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Lambung
Mangkurat University, Banjarmasin, South Kalimantan, Indonesia

43
Submitted: 31-07-2024; Received in Revised Form: 15-08-2024; Accepted: 13-05-2025

Sari et al.

INTRODUCTION
The global prevalence of chronic kidney disease is 9.5%, with a mortality rate of 2.4%
(ISN, 2023). Chronic kidney disease is a health challenge in various countries, including
Indonesia (Hustrini, 2023). One of the provinces in Indonesia, South Kalimantan, has a
significant prevalence of chronic kidney disease. The population of chronic kidney disease
patients in South Kalimantan in 2021 showed that the number of old cases was 430 people,
with 347 new cases. Among these chronic kidney disease patients, 20 people died in 2021
(South Kalimantan Province, 2021).
Patients with chronic kidney disease need to undergo continuous pharmacological
therapy to maintain the physiological viability of the kidneys, increase the patient’s life
expectancy, and avoid other disease complications. A group of diseases that can occur
includes anemia, metabolic acidosis, diabetes mellitus, pulmonary edema, electrolyte fluid
disorders, hypertension, hyperkalemia, and bone disorders. Complications of these
diseases lead patients to take a large number of drugs, leading to polypharmacy. The large
number of drugs that patients must consume increases the risk of adverse drug reactions
(ADRs) caused by drug-drug interactions. The impact of drug interactions on the
pharmacokinetic and pharmacodynamic properties of a drug that experiences drug
interactions, in addition to drug interactions in patients with chronic kidney disease, can
cause multiple organ dysfunction and excess extracellular fluid. It is important to identify
the risk of drug-drug interactions to mitigate the increased incidence of morbidity and
mortality (Hammoud et al., 2022; Hutagaol, 2017; Narsa et al., 2022; Papotti et al., 2021).
Potential drug interactions can be identified by reviewing the literature and using
tools. The Lexicomp® application presents a service to identify the risk of drug interactions
with other drugs. According to the study by Marcath et al., Lexicomp could identify one
more clinically meaningful interaction among 33.3 patients instead of existing medication
interaction approaches (Marcath et al., 2018). Lexicomp® scores well compared to other
tools in identifying the risk of drug interactions based on sensitivity, specificity, and
performance (Shakeel et al., 2020). Identification of drug interactions with drugs in
patients with chronic kidney disease in Indonesia has been studied primarily using the
www.drugs.com application (Handayani et al., 2023; Probosiwi et al., 2023; Santosa et al.,
2024). The Lexicomp® application provides information on potential drug interactions
with drugs based on the level of risk, severity, and recommendations for limiting drug
interactions (Lexicomp, 2024). The advantages of the Lexicomp® application include
references to each search, a simple design, and a layout that makes it easier for readers to
read the information displayed and can be accessed without a cellular signal. Based on this,
the study aims to identify potential drug interactions with drugs for patients with chronic
kidney disease using the Lexicomp® application in the aspects of risk level, severity, and
recommendations for limiting drug interactions. It is hoped that it can describe the safety
of drugs and the handling of potential drug interactions to minimize the incidence of drug
interactions in patients with chronic renal failure. The researcher provides data on
identifying potential drug interactions using Medscape®, Drugs.com®, and DrugBank®
tools to enhance health worker awareness and encourage consideration of drug interaction
tools in their practice.

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METHODS
The study was conducted at Ansari Saleh Hospital, Banjarmasin, South Kalimantan,
from January to February 2024. Data collection was retrospective, tracking patient
electronic medical record data. The study population used data from the electronic medical
record of inpatients diagnosed with chronic kidney disease at Ansari Saleh Banjarmasin
Hospital from January to December 2023. The sampling technique used in this study was
total sampling. The sample is data from the electronic medical record of hospitalized with
chronic kidney disease at Ansari Saleh Banjarmasin Hospital for January-December 2023
who meet the research criteria. The following inclusion criteria were patients with a
primary diagnosis of kidney disease (ICD N.18), hospitalized and prescribed ≥ 2 drugs. The
researchers excluded samples with referral status to other hospitals or death. Research
instruments consisted of data collection sheets and the Lexicomp® application.
Data Analysis
Data analysis using the Lexicomp® application obtained data on potential drug
interactions. Lexicomp® is a paid access application. Relevant Lexicomp® information can
be accessed at the following link: http://webstore.lexi.com/Information/ProductInformation/Lexi-Interact-Fields. The risk level in the Lexicomp® application is classified
as A, B, C, D, and X. Severity levels in the Lexicomp® application are divided into minor,
moderate, and major. Restriction recommendations are described for each drug based on
the Lexicomp® application.
RESULT AND DISCUSSION
Based on data from medical records, 67 medical records were found in the period
January - December 2023. Nine medical records were excluded from the study because the
primary diagnosis was not kidney disease, resulting in a total of 58 samples that were used
for analysis.
This study involved a total sample of 58 participants, of whom 33 experienced
potential drug interactions. A total of 25 patients did not experience potential drug
interactions. The results showed that patients who potentially experienced drug
interactions were more, namely 56.90%, compared to patients who did not experience
potential drug interactions, namely 43.10%. The results of this study indicate that the
percentage of drug interactions possible in patients with chronic kidney disease is lower
than in previous studies. The results of the research by Primadhini et al. stated that chronic
renal failure patients who had the potential to experience drug interactions were 106
patients, or 95%, while those who did not have the potential to experience drug
interactions were six patients, or 5% (Primadhini et al., 2023). The difference in the number
of patients analyzed causes differences in the percentage of potential drug interactions. The
potential drug interaction with most drugs is Iron-Omeprazole.
Based on the results obtained, 33 patients who experienced potential drug
interactions and 175 cases of potential drug interactions, with 53 drug combinations of
potential drug interactions, were obtained. This study identified various levels of risk of
possible drug interactions according to categories. Most were in category C. Potential drug
interactions based on the level of risk in the Lexicomp® application are divided into five
levels, namely A, B, C, D, and X, from a total of 175 cases of drug interactions that occurred
(Table 1). Category X indicates a very high risk and is generally contraindicated; an example
is the combination of Flunarizine with Cetirizine, which can increase sedation in certain
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Sari et al.

patients (Lule et al., 2024). On the other hand, Category D requires alternative therapy or
close monitoring, such as the combination of furosemide with ketorolac, which can increase
the risk of kidney damage. Category C shows significant effects that can still be used with
monitoring, such as combining Ceftriaxone with Furosemide, which can trigger
nephrotoxicity.
Table 1. The Percentage of Potential Interaction Data (PID) Based on Risk Level

PID Based on Risk Level
A
B
C
D
X
Total

Frequency
0
55
108
7
5
175

Percentage (%)
0
31.43
61.71
4
2.86
100

Category B shows evidence of potential drug interactions with little clinical support,
such as the combination of Uron with Omeprazole, which may increase the risk of anemia.
Combining iron with PPIs (Omeprazole and Lansoprazole) has potential drug interactions
in the absorption phase of pharmacokinetics. Iron is used to increase hemoglobin and
serum ferritin in patients with anemia, while PPI inhibits gastric acid production by
activating the enzyme H⁺, K⁺, -ATPase from parietal cells (Kapoh et al., 2021; Syari & Sari,
2021). This interaction results in decreased iron absorption due to increased
gastrointestinal pH, which can decrease serum concentrations and the effectiveness of iron
therapy, potentially damaging patients with anemia (Drugbank, 2024; Lexicomp, 2024).
Category A shows no evidence of significant drug interactions and does not require a
specific intervention. The current study did not find category A risk (Sari & Putra, 2024b).
Chronic renal failure patients revealed a potential drug interaction at risk level X,
according to the findings of Aghili and Kasturirangan. Two combinations of medications
found in the study showed possible drug interactions at risk level X. Generally
contraindicated in providing the drug combination, the combination of drugs at risk level
X should be avoided for the use of the drug, as the gained dangers are greater than the
benefits (Aghili & Kasturirangan, 2021). Table 1 presents the percentage of potential
interaction data categorized by risk level.
Most potential drug interactions fall into the moderate severity category. The results
of the current study align with previous studies (Sari & Putra, 2024b; Susanti et al., 2023).
Potential drug interactions based on severity in the Lexicomp® application are divided into
3, namely minor, moderate, and major. Potential drug interactions based on the severity of
the drug can cause injury or permanent damage and even threaten the patient’s life,
requiring contraindications in combination use, such as Clopidogrel with Lansoprazole,
which interferes with the antiplatelet effect of Clopidogrel (Lexicomp, 2024). As a
thienopyridine prodrug, Clopidogrel requires the metabolism of active metabolites by the
enzyme CYP2C19. As a proton pump inhibitor (PPI), lansoprazole inhibits CYP2C19
enzymes by increasing gastric pH. This interaction results in a decrease in the area under
the curve of the active metabolite of Clopidogrel by approximately 14%, which can reduce
the therapeutic effect and increase the risk of complications such as heart attack after
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myocardial infarction or post-percutaneous coronary intervention stent thrombosis
(Lexicomp, 2024; Maifitrianti, 2016).
Moderate-level interactions, such as Ceftriaxone with Furosemide, require
monitoring, as they can increase the risk of kidney damage (Agustin & Fitrianingsih, 2020;
Hakim & Arfania, 2022; Lexicomp, 2024). The findings of this study align with previous
research indicating that the combination of Ceftriaxone and Furosemide has the highest
potential for moderate-severity drug-drug interactions (Sari & Putra, 2024a). Furosemide
is a pharmacological agent classified as a loop diuretic, prescribed primarily for treating
hypertension and cardiovascular disease. Individuals with chronic kidney disease
generally require diuretics to regulate fluid expansion outside cells and to reduce blood
pressure (Sari et al., 2023). Potential interaction in this drug combination involves a
mechanism where furosemide can increase the risk of nephrotoxicity, particularly when
used with the cephalosporin class of antibiotics (Lexicomp, 2024). Although interactions at
a minor level, such as iron with omeprazole, generally do not require intervention, they still
need attention to avoid the risk of anemia (Lexicomp, 2024). Table 2 shows the percentage
of potential drug interactions, stratified by severity.
Table 2. Percentage of potential drug interactions based on severity

PID Based on Severity
Minor
Moderate
Major
Total

Frequency
59
109
7
175

Percentage (%)
33.71
62.29
4
100

This study found that most patients with chronic kidney disease experienced drug
interactions classified as risk category C, indicating moderate severity. Several factors are
significantly associated with the incidence of drug-drug interactions, including age, the
number of drugs, and the length of hospitalization (Sari et al., 2023; Sari & Putra, 2024).
Age is associated with the incidence of drug interactions; An age over 60 has greater
potential than an age less than 60. The elderly experience a physiological decline in the
body that affects the pharmacokinetic and pharmacodynamic processes of the drugs
consumed. The quantity of drugs taken influences the appearance of drug interactions. An
increase in the number of drugs used by a patient is correlated with a higher risk of drug
interactions. The duration of hospitalization is positively correlated with the potential for
drug interactions (Sari et al., 2023).
Recommendations for handling drug interactions with drugs in patients with drug
interactions are important to prevent unwanted reactions. Avoid drug combinations with
potential interactions and perform clinical management by monitoring specific health
parameters such as blood pressure, heart rate, and hypersensitivity reactions. In drug
combinations with risk of category C and moderate to significant severity, such as
Ceftriaxone-Furosemide, Amlodipine-Furosemide, Candesartan-Potassium Chloride,
Diltiazem-Furosemide, Allopurinol-Furosemide, Clonidine-Diltiazem and ClopidogrelLansoprazole, therapeutic monitoring and dose adjustment should be considered if
necessary (Lexicomp, 2024). Most recommendations to handle potential drug interactions
are monitoring therapy and dose adjustments. Table 3 provides recommendations for
managing potential drug interactions of moderate and severe severity.
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Table 3. Recommendations for handling PDI Based on Risk and Severity Level
Combination of PDI
Risk
Severity
No
Handling PDI
(%)
Level
Level
Monitor high-dose drug use, particularly in
geriatric patients. Assess renal function and
Ceftriaxonecalculate the rate of glomerular filtration.
1
C
Moderate
furosemide (6.86%)
Implement a 3-4 hour interval before
administering cephalosporin class drugs in
combination therapy.
Monitoring of blood pressure and possible
Amlodipine2
C
Moderate
adjustment of antihypertensive dosage may
Furosemide (4.57%)
be necessary.
CandesartanObserve for indicators of hyperkalemia.
3
potassium chloride
C
Moderate
(4%)
Monitoring of blood pressure and possible
Diltiazem4
C
Moderate
adjustment of antihypertensive dose may be
Furosemide (3.43%)
necessary.
AllopurinolObserve for indications of hypersensitivity
5
Fluoroquinolones
C
Moderate
reactions, including fever, rash, and
(2.86%)
eosinophilia, as well as other adverse effects.
Closely monitor heart rate and blood
Clonidine-Diltiazem
pressure and inform the patient about the
6
C
Moderate
(2.86%)
potential onset of new or worsening
bradycardia.
Observe respiratory depression and other
Codeine-fluconazole
adverse effects of the medication and
7
C
Moderate
(2.86%)
consider decreasing the codeine dosage until
a stable therapeutic effect is achieved.
FurosemideObserve for indications of hypotension.
8
C
Moderate
Lisinopril (2.86%)
FurosemideObserve for indications of hypotension.
9
C
Moderate
Ramipril (2.86%)
CandesartanA decrease in the dose of antihypertensive
10
C
Moderate
Flunarizine (2.86%)
medication may be necessary.
ClopidogrelAssess clopidogrel pharmacodynamic
11
Lansoprazole
C
Major
response
(2.86%)
Observe the enhanced nephrotoxic effects
Gentamicin12
C
Moderate
associated with aminoglycosides.
Ketorolac (1.14%)
13

BetahistineCetirizine (1.14%)

14

Acarbose-Insulin
detemir (0.57%)

D

Moderate

15

FurosemideKetorolac (0.57%)

D

Moderate

C

Moderate

Assess the decline in therapeutic efficacy.
Evaluate the reduction in insulin dose upon
starting therapy with alpha-glucosidase
inhibitors and observe the patient for
hypoglycemia.
Assess the decreased therapeutic efficacy of
loop diuretics.

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No

Combination of PDI
(%)

Risk
Level

Severity
Level

16

Metamizole sodium
furosemide (0.57%)

D

Moderate

17

Cetirizineflunarizine (2.28%)

X

Moderate

18

Metamizole sodium
ketorolac (0.57%)

X

Major

Handling PDI
Assess the decreased therapeutic efficacy of
loop diuretics.
Nervous system depressants are
contraindicated during flunarizine treatment.
Ketorolac should not be administered in
conjunction with other non-steroidal antiinflammatory drugs (NSAIDs).

Identification of potential drug interactions can also be analyzed through other tools
such as Medscape®, Drugs.com®, com®, and DrugBank®. All three tools are available
online and can be accessed free of charge. Medscape®, Drugs.com®, com®, com®, and
DrugBank® provide information on the detection of potential drug interactions based on
severity (Marcath et al., 2018). The current study presents the results of analyzing potential
drug interactions based on these three tools (Table 4 and 5). Therefore, it can provide an
overview of potential drug interactions in patients with chronic kidney disease using
different tools to detect drug interactions. In addition, it shows the consistency of drug
interaction data available from various tools. Therefore, it can serve as a valuable resource
for health workers, particularly in Indonesia, to identify drug-drug interactions in patients
with chronic kidney disease. Pharmacists should identify drug interactions in
pharmaceutical services and know how to handle them.
Table 4. PDI by severity based on Medscape®, Drugs.com®, and DrugBank®
No
1

2
3
4
5
6

Combination of PDI
(%)
CeftriaxoneFurosemide
(6.857%)
AmlodipineFurosemide
(4.571%)
CandesartanPotassium Chloride
(4%)
DiltiazemFurosemide
(3.429%)
AllopurinolFluoroquinolones
(2.857%)
Clonidine-Diltiazem
(2.857%)

Medscape®

Drugs.com®

DrugBank®

Minor

Moderate

Minor

There are no
interactions with other
drugs

There are no
interactions with
other drugs

Minor

-

Major

Moderate

There are no
interactions with other
drugs
There are no
interactions with other
drugs

There are no
interactions with
other drugs

Minor

Moderate

Moderate

Major

Moderate

Moderate

7

Codeine-Fluconazole
(2.857%)

There are no
interactions with other
drugs

There are no
interactions with
other drugs

Moderate

8

FurosemideLisinopril (2.857%)

Moderate

Moderate

Moderate

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No

Combination of PDI
(%)

9

FurosemideRamipril (2.857%)

10

11
12
13
14
15
16
17
18

CandesartanFlunarizine
(2.857%)
ClopidogrelLansoprazole
(2.857%)
GentamicinKetorolac (1.143%)
BetahistineCetirizine (1.143%)
Acarbose-Insulin
detemir (0.571%)
FurosemideKetorolac (0.571%)
Metamizole sodiumFurosemide
(0.571%)
CetirizineFlunarizine (2.28%)
Metamizole sodiumketorolac (0.571%)

Medscape®

Drugs.com®

DrugBank®

Moderate

Moderate

There are no
interactions
with other
drugs.

-

-

Minor

Moderate

Moderate

Moderate

Minor

Moderate

Moderate

-

-

Moderate

Moderate

There are no
interactions with
other drugs.

Moderate

Minor

Moderate

Moderate

-

-

Moderate

-

-

Moderate

-

-

Moderate

Identifying drug interactions of chronic kidney disease patients according to severity
shows differences in results between tools for detecting potential drug interactions. More
research is needed to compare tools for detecting potential drug interactions, especially in
the use of drugs for patients with kidney disease. Therefore, reliable tools for detecting
drug interactions can be obtained for health workers in health facilities. In addition,
regarding recommendations for handling potential drug interactions, the Lexicomp® tools
are the most complete for providing information. However, the DrugBank® tool provides
minimal information on treatment recommendations. DrugBank® tools can be used to find
information on severity and mechanism.
Table 5. Recommendations for the handling of PDI Based on Medscape®, Drugs.com®,
and DrugBank®
Combination of PDI
No
Medscape®
Drugs.com®
DrugBank®
(%)
CeftriaxoneAdjustment of
1
Furosemide (6.857%)
dosage is necessary
Amlodipine2
Furosemide (4.571%)

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No
3
4

Combination of PDI
(%)
CandesartanPotassium Chloride
(4%)
DiltiazemFurosemide (3.429%)

Medscape®

Drugs.com®

DrugBank®

Therapy monitoring
required

Adjustment of
dosage is necessary

-

-

-

-

5

AllopurinolFluoroquinolones
(2.857%)

-

6

Clonidine-Diltiazem
(2.857%)

Refrain from the
concurrent use or
alternation of drugs
where feasible.

Require monitoring
of therapy or
cessation of
allopurinol use
Requirement for
dose modification
or therapeutic
oversight

-

-

Therapy monitoring
required
Therapy monitoring
required

Adjustment of
dosage is necessary.
Adjustment of the
dose is necessary.

-

-

7
8
9
10
11
12
13
14
15
16
17
18

Codeine-Fluconazole
(2.857%)
FurosemideLisinopril (2.857%)
Furosemide-Ramipril
(2.857%)
CandesartanFlunarizine (2.857%)
ClopidogrelLansoprazole
(2.857%)
Gentamicin-Ketorolac
(1.143%)
Betahistine-Cetirizine
(1.143%)
Acarbose-Insulin
detemir (0.571%)
FurosemideKetorolac (0.571%)
Metamizole sodiumFurosemide (0.571%)
Cetirizine-Flunarizine
(2.28%)
Metamizole sodiumketorolac (0.571%)

-

-

Therapy monitoring
required

Consider altering
the medication if
possible
Therapy follow-up
required

-

-

-

Therapy monitoring
required

-

Follow-up of
therapy required
Therapy monitoring
required.

-

-

Adjustment of the
dosage is necessary.

-

-

-

-

-

-

-

-

-

-

The study's limitations encompass a restricted sample size and data confined to
individuals documented in the electronic medical record. Future research should
investigate pharmacist knowledge, attitudes, and actions regarding identifying probable
drug-drug interactions.

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CONCLUSION
When using the Lexicomp® application, it is important to consider the risk level of
most category C drugs, the severity of most moderate interactions, and recommendations
for limiting drug interactions; therefore, potential drug interactions with medications for
patients with chronic kidney disease often require monitoring and dose adjustments.
ACKNOWLEDGEMENT
The study team would like to thank all those who contributed to the project's
completion.
PNBP PDWM ULM grant funds secured for 2023 (SP
066.159/UN8.2/PG/2023).
AUTHOR CONTRIBUTION
OMS: Ideas, design, literature search, data analysis, manuscript preparation, and
manuscript editing.
PNA: Data collection; data analysis.
AMPP: Design; Definition of intellectual content.
ETHICS APPROVAL
The research design obtained a recommendation of eligibility from the Research Ethics
Commission Team of the Faculty of Pharmacy of Muhammadiyah University of
Banjarmasin, with No. 031/UMB/KE/I/2024.
CONFLICT OF INTEREST (If any)
None to declare.
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