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

Study of Drug Interactions in Cancer Therapy and Their
Management in Cancer Patients at the Outpatient
Polyclinic of General Hospital “X” in 2020
Anak Agung Ngurah Putra Riana Prasetya1*, Mahadri Dhrik2, Pande Made Desy
Ratnasari1, Ni Luh Sri Adi Suryani1
1 Bachelor of Pharmacy Study Program, Sekolah Tinggi Farmasi Mahaganesha, Denpasar, Bali, Indonesia
2 Diploma of Pharmacy Study Program, Sekolah Tinggi Farmasi Mahaganesha, Denpasar, Bali, Indonesia

ABSTRACT: Chemotherapy is commonly used in cancer patients either as a monotherapy or
in combination, as it demonstrates higher effectiveness and lower toxicity compared to singleagent use, while also preventing drug resistance. The combination of chemotherapy drugs, or
their use alongside supportive drugs, can increase the risk of drug interactions that may affect
treatment outcomes. The purpose of this research is to examine and offer suggestions for the
management of medication interactions in cancer patients at the X Cancer Centre polyclinic of
X Denpasar Hospital in 2020. The present investigation is a cross-sectional descriptive study
with retrospective data collection from medical records in 2020. Drug interaction data were
analyzed using Drugs.com, Lexicomp, and Stockley to assess the type of interaction, risk level,
severity, and management of each interaction. The results indicated that the most common
types of cancer were breast cancer (62.7%) and lymphoma (10.2%), with combination
chemotherapy being used in 73.97% of cases. The most frequent type of interaction was
pharmacodynamic interaction (50.42%), with risk level C (35.53%) and moderate severity
(69.07%). The most common interactions were between chemotherapy drugs and supportive
drugs (46.47%). The recommended management of potential drug interactions in cancer
patients includes providing a time gap between drug administrations.
Keywords: Drug interactions; cancer; chemotherapy

*Corresponding author:

Name
: Anak Agung Ngurah Putra Riana Prasetya
Email
: gungtra.apoteker95@gmail.com
Address : Sekolah Tinggi Farmasi Mahaganesha, Denpasar, Bali, Indonesia

23
Submitted: 12-07-2024.; Received in Revised Form: 07-10-2024 .; Accepted: 10-05-2025

Prasetya et al.

INTRODUCTION
Cancer is a condition involving the abnormal growth of body cells that can develop
and spread to other parts of the body, disrupting organ growth and potentially leading to
death (Yeoh et al., 2015). Cancer patients in the world are estimated to reach 19.3 million
cases, with 10 million deaths, and as many as 68 thousand cases of breast cancer are found
in Indonesia, with 22 thousand deaths. Common cancer cases in Indonesia are lung cancer,
breast cancer, prostate cancer, colorectal cancer, stomach cancer, and liver cancer (Firdaus
& Susilowati, 2023; Sung et al., 2021). The growth and development of cancer cells are
influenced by the disruptions in deoxyribonucleic acid (DNA) formation, which triggers
abnormalities in gene division (gene mutation). Several factors contribute to cancer cell
growth, including exposure to carcinogenic substances, oncogenic viruses, environmental
factors, economic factors, diet, and alcohol consumption (Alipour, 2021; Sun et al., 2020).
Chemotherapy is one of the commonly used methods as an anticancer agent, used
singly or in combination, with a mechanism of action that suppresses proliferation, spread
and destroys cancer cells (cytotoxic). The cytotoxic effect of chemotherapy drugs destroys
cancer cells and affects normal cells, which can lead to harmful side effects (Firdaus &
Susilowati, 2023). Combinations of chemotherapy drugs are commonly used because they
are more effective and have lower toxicity compared to single-agent use, and they can
prevent or slow drug resistance (Rusdi et al., 2023). Another widely used treatment
approach is the combination of chemotherapy drugs with supportive drugs, which are used
as premedication before chemotherapy and as post-chemotherapy therapy.
The use of drug combinations can cause drug-related problems (DRP). Drug-related
problems (DRP) are unexpected events caused by treatment that can potentially affect and
disrupt the success of therapy. One of the issues within DRPs is drug interactions, which
can affect clinical outcomes during treatment (Mantang et al., 2023). Drug interactions are
categorised into three types, namely pharmaceutical interactions, pharmacokinetic
interactions, and pharmacodynamic interactions. Drug interactions may occur due to
excessive drug use in a single prescription, known as polypharmacy. Another study
reported that the incidence of DRP due to ineffective medication was 26.67%, and due to
drug interactions was 66.67% (Nayak et al., 2021).
Based on this, several studies on drug interactions in cancer patients have been
conducted. One study found that the potential for drug interactions in cancer patients at X
West Java hospital from 2019 to 2021 involved 428 cases, with 88.17% having moderate
significance (Rusdi et al., 2023). Another study mentioned that prescribing more than
seven types of drugs, or three or more types of cancer drugs, carries a high risk of drug
interactions (Ismail et al., 2020). Another study examining drug interactions in cancer
patients found that 50.1% of drug interactions were caused by pharmacodynamic
mechanisms, 27% by pharmacokinetic mechanisms, and 23.6% had an unknown
interaction mechanism (Ramasubbu et al., 2021).
Based on these studies, the high potential for drug interactions during treatment can
affect treatment outcomes and increase the risk of side effects. Drug interactions can be
mitigated by assessing the interactions of the drugs given to cancer patients (Faizah, 2018).
Thus, the purpose of this study was to evaluate the possibility of drug interactions and offer
suggestions for handling drug interaction incidents in cancer patients at the X General
Hospital Denpasar's X Cancer Centre outpatient clinic over the course of 2020.
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METHODS
Research Design
This study used an observational cross-sectional design and employed descriptive
methods with retrospective data collection from the outpatient polyclinic at X Cancer
Center, X Denpasar General Hospital. The study population and sample included all medical
records and pharmacy data of patients diagnosed with cancer who underwent
chemotherapy in 2020.
Sampling Technique
The sampling technique in this study uses purposive sampling with specific
considerations in sampling. The inclusion criteria in the study were cancer patients
undergoing outpatient chemotherapy who had complete drug data (chemotherapy
regimen, premedication drugs, and post-chemotherapy). The exclusion criteria were
patients undergoing chemotherapy whose medical records had unclear or unreadable drug
names, and cancer patients undergoing chemotherapy did not receive premedication
therapy or post-chemotherapy drugs. Based on the inclusion and exclusion criteria, a total
of 118 samples were obtained.
Research Instruments
The research instrument used was a data collection table containing the patient's
name initials, medical record number, gender, chemotherapy drugs used, premedication
drugs, and post-chemotherapy drugs, which would later be placed in the drug interaction
assessment analysis table. The data obtained was stored using the Microsoft Excel
application. The type of data used was quantitative data, which included patient population
data, chemotherapy drugs used, and drugs used before and after undergoing
chemotherapy.
Data Analysis
Demographic and drug interaction data were analyzed descriptively using a
percentage table. Analysis of patient demographics included data on gender, age,
occupation, and type of cancer experienced by the patient, while the drug interactions
analysis was determined based on the significance standards found on the official website
of Lexicomp (2023), Drugs.com (2023), and Stocktey's Drug Interactions (2015). Drug
interaction analysis was conducted by comparing interactions that occurred in patients
with those recorded in the literature. The percentage of drug interactions was determined
based on the types of drug interactions that occurred, the level of risk factors set by the
Food and Drug Administration (FDA), and the significance of interactions from several risk
factors reviewed based on the severity caused by drug interactions (severity). The
following equation was used in calculating the percentage of drug interaction events and
the significance of interactions is as follows:
%Potential drug interactions = 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑡𝑦𝑝𝑒𝑠 𝑥 100%
𝑇𝑜𝑡𝑎𝑙 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛𝑠

%Potential drug interactions based on significance=
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛𝑠 𝑏𝑦 𝑠𝑖𝑔𝑛𝑖𝑓𝑖𝑐𝑎𝑛𝑐𝑒 𝑐𝑎𝑡𝑒𝑔𝑜𝑟𝑦
𝑥 100%
𝑇𝑜𝑡𝑎𝑙 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛𝑠 𝑏𝑦 𝑠𝑖𝑔𝑛𝑖𝑓𝑖𝑐𝑎𝑛𝑐𝑒 𝑐𝑎𝑡𝑒𝑔𝑜𝑟𝑦

Analysis of drug interactions based on the level of risk is grouped into several
categories: category A indicates that there is no evidence of drug interactions, category B
indicates evidence of potential drug interactions with little clinical effect, category C
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Prasetya et al.

indicates clinical significance so that monitoring is required, Category D indicates the need
for changes (dose, alternative therapy, or monitoring) and Category X indicates that
avoiding it is advisable due to its high risk. Meanwhile, severity-based analysis classified
interactions as major (potentially causing death or permanent disability), moderate
(resulting in clinical status changes), or minor (with negligible effects that do not require
additional therapy) (Shetty et al., 2018; Yuliawati et al., 2021). This study also included
management recommendations for each identified drug interaction as supporting data.
RESULT AND DISCUSSION
Characteristics Sample
A total of 118 samples met the inclusion criteria of cancer patients undergoing
outpatient chemotherapy at the X Cancer Center Polyclinic, X Denpasar General Hospital,
in 2020. Table 1 shows that the highest average age of cancer patients falls within the 44 to
53 year range (32%), with a higher proportion of female patients (82%) compared to male
patients (18%). Females are at greater risk of developing cancer due to hormonal
influences, such as estrogen, which plays a role in regulating menstruation and the
menopausal process. Prolonged exposure to this hormone can increase cancer risk
(Hasnita & Arif Harahap, 2019; Wardana & Ernawati, 2019). Twelve types of cancer were
identified among the patients, with the most common being breast cancer (62.7%), nonHodgkin lymphoma (10.2%), rectal cancer (7.6%), and colorectal cancer (5.9%). Previous
studies have shown that most breast cancer cases occur between the ages of 45 and 64, due
to the increased cancer risk associated with aging and accumulated genetic damage (Elmika
& Adi, 2020; Sari & Gumayesty, 2016).
Drug Utilization Profile
Chemotherapy drugs are cytostatic agents used to inhibit the proliferation of cancer
cells and induce cell destruction. These drugs, whether used as monotherapy or in
combination, are commonly administered to cancer patients (Firdaus & Susilowati, 2023).
At X General Hospital, chemotherapy regimens include both monotherapy and combination
therapy. This study found that 26.03% of patients received chemotherapy as monotherapy,
while 73.97% were treated with combinations of two or more chemotherapy drugs.
Based on the data in Table 2, the most frequently used combination of two chemotherapy
drugs was carboplatin and paclitaxel, accounting for 7.32%. This combination is commonly
used in patients with triple-negative breast cancer (TNBC), an aggressive form of breast
cancer that does not respond to standard therapies. TNBC lacks the expression of several
receptors, such as progesterone and estrogen receptors, but often involves overexpression
of the Human Epidermal Growth Factor Receptor 2 (HER-2), a receptor that regulates cell
growth and repair in breast tissue (Amtiria et al., 2018; Permana et al., 2019; Yu et al.,
2020).
This study also identified combinations involving three chemotherapy drugs, with
the most common being 5-Fluorouracil, Doxorubicin, and Cyclophosphamide, used in
13.82% of cases. This regimen significantly reduces the risk of breast cancer recurrence by
interfering with DNA replication during the cancer cell development cycle. It is typically
administered intravenously every three weeks for six cycles (Irawati & Sardjan, 2022;
Pereira-Oliveira et al., 2019). The use of combination chemotherapy aims to improve

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tolerability and effectiveness while reducing drug resistance in cancer patients (Wu et al.,
2020).
Table 1. Patients Demographics
Patient Demographics
age
24 – 33
34 – 43
44 – 53
54 - 63
64 - 73
Total
Sex
Female
Male
Total
Type Cancer
Breast Cancer
Non-Hodgkin's Lymphoma
Rectal Cancer
Colon Cancer
Cervical Cancer
Ovariun Cancer
Plasma Cell Cancer
Nasopharyngeal Cancer
Blood Cancer
Esophageal Cancer
Lung Cancer
Prostat Cancere
Total
Table 2. Chemotherapy Drugs Used
Drug
Monotherapy
Trastuzumab
Gemcitabine
Paclitaxel
Capecitabine
Bevacizumab
Other
Total
2 Combination Therapy
Carboplatin + Paclitaxel
Doxorubicin + Paclitaxel
Capecitabine + Oxalipatin
Cyclophosphamide + Doxorubicin
Paclitaxel + Trastuzumab
Pertuzumab + Trastuzumab
Other

Total
6
25
38
34
15
118
97
21
118
74
12
9
7
4
3
3
2
1
1
1
1
118

%
5
21
32
29
13
100
82
18
100
62.7
10.2
7.6
5.9
3.4
2.5
2.5
1.7
0.8
0.8
0.8
0.8
100

Total

%

7
5
4
4
3
9

5.69%
4.09%
3.25%
3.25%
2.44%
7.31%
26.03%

9
9
8
5
3
3
15

7.32%
7.32%
6.50%
4.07%
2.44%
2.44%
12.19%

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Prasetya et al.

Drug
3 Combination Therapy
5-Fluorouracil + Doxorubicin + Cyclophosphamide
Doxorubicin + Cyclophosphamide + Vincristine
5-Fluorouracil + Irinotecan + Leucovorin
Doxorubicin + Paclitaxel + Trastuzumab
Other
4 Combination Therapy
5-Fluorouracil + Bevacizumab + Leucovorin + Oxaliplatin
Total
Total Monotherapy + Combination Therapy

Total

%

17
11
3
2
5

13.82%
8.94%
2.44%
1.63%
4.05%

1

0.81%
73.97%
100%

In addition to chemotherapy drugs, cancer patients commonly use supportive
medications (Table 3) to reduce or manage the side effects caused by chemotherapy. These
supportive therapies include drugs administered before (premedication) and after (postmedication) chemotherapy. The most frequently used supportive drugs were
antihistamines (31.61%), corticosteroids (31.31%), and 5-HT3 receptor antagonists
(21.88%). First-generation antihistamines are commonly used in cancer patients
undergoing chemotherapy to manage hypersensitivity reactions and side effects associated
with chemotherapy drugs (Fritz et al., 2021). Other studies have also reported that the use
of antihistamines (e.g., diphenhydramine), corticosteroids (e.g., dexamethasone), and 5HT3 receptor antagonists (e.g., ondansetron) effectively reduces and controls
chemotherapy-induced nausea and vomiting (Shinta R & Surarso, 2016).
Table 3. The usage of other drugs
Drug
Antihistamine
Corticosteroids
5-HT3 Receptor Antagonists
Supplement
Proton Pump Inhibitor (PPI)
Analgesics
Anticoagulan
H2 Antagonist
Other
Total

Total
104
103
72
26
9
6
1
1
7
329

%
31,61%
31,31%
21,88%
7,90%
2,74%
1,82%
0,30%
0,30%
2,13%
100%

Drug Interaction Assessment
The use of chemotherapy drugs in combination with supportive therapy in cancer
patients carries a high risk of drug interactions. This potential arises from the concurrent
use of multiple medications, often due to comorbidities and the advanced age of patients
(Rabba et al., 2020; Riechelmann & Krzyzanowska, 2019). Studying drug interactions is
essential for estimating potential risks and planning appropriate management strategies to
reduce or prevent adverse interactions (Hammad et al., 2017).
This study reviewed drug interactions in cancer patients undergoing chemotherapy using
both free and paid resources, such as Drugs.com, Lexicomp, and Stockley's Drug
Interactions. The results indicated that the most common type of interaction was
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pharmacodynamic (50.42%). Similar findings were reported in another study, where
pharmacodynamic interactions accounted for 50.1%, surpassing pharmacokinetic (26.6%)
and unknown (23.3%) interactions (Ramasubbu et al., 2021). One example of a
pharmacodynamic interaction identified in this study was between doxorubicin and 5fluorouracil, which can lead to myelosuppression and gastrointestinal bleeding (Nayak et
al., 2021).
Pharmacodynamic interactions occur when two drugs share similar or opposing
pharmacological targets, therapeutic effects, or side effects. These interactions typically
involve active compounds that mutually alter pharmacological effects, either reinforcing,
adding to, or antagonizing each other, leading to unwanted reactions (Ramdani et al., 2022).
Another type of potential interaction observed was pharmacokinetic, accounting for
27.97%. An example of this interaction is between doxorubicin and dexamethasone, where
dexamethasone may decrease the blood levels of doxorubicin (Drug.com, 2023).
Pharmacokinetic interactions occur when one drug affects the absorption, distribution,
metabolism, or excretion of another drug, altering plasma concentrations. This effect can
result from the inhibition or induction of cytochrome P450 (CYP) enzymes in the body
(Rizo et al., 2020).
The assessment of drug interactions based on risk level is categorized into five
groups: A, B, C, D, and X. As shown in Table 4, the most common risk levels were C (35.53%)
and D (34.21%). Based on severity, drug interactions can be classified as major, moderate,
or minor. Major interactions have significant clinical consequences, moderate interactions
can alter the patient's clinical status, and minor interactions cause mild disturbances that
do not substantially affect therapeutic outcomes (Feinstein et al., 2015). The most frequent
interaction severity in this study was moderate (69.07%).
Table 4. Potential Interaction Characteristics
Characteristic
Type Interactions
Pharmacodynamic
Pharmacokinetic
Unknown
Total
Risk Level
C
D
B
Total
Severity
Moderate
Mayor
Minor
Total

%
50.42%
27.97%
21.61%
100%
35.53%
34.21%
30.26%
100%
69.07%
19.49%
11.44%
100%

Table 5 shows that the potential for drug interactions is higher in the combination of
chemotherapy drugs and supportive drugs (46.47%) than in the interaction between
chemotherapy drugs alone (41.08%) or between supportive drugs alone (12.45%). Similar
findings have been reported in other studies, which also indicated that the potential for
drug interactions was higher when chemotherapy drugs were combined with supportive
drugs (Laban et al., 2021). The combination of dexamethasone and paclitaxel (25%) was
the most frequently observed drug interaction in cancer patients, followed by the
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combination of cyclophosphamide and ondansetron (18.75%), and the interaction between
doxorubicin and dexamethasone (11.61%). The interaction between dexamethasone and
paclitaxel is a pharmacokinetic interaction with moderate severity. Dexamethasone is an
inducer of the cytochrome P450 enzyme CYP3A4, which can lower paclitaxel levels in the
blood, thus reducing its effectiveness. Management strategies include monitoring the
therapeutic response to paclitaxel, administering dexamethasone 30 minutes prior to
paclitaxel infusion, and using dexamethasone as premedication to reduce the risk of
hypersensitivity reactions caused by paclitaxel (D’Errico et al., 2020).
We classify the interaction between cyclophosphamide and ondansetron as an unknown
interaction of minor severity, with a risk level of B. Ondansetron may reduce the
pharmacological effects and alter the systemic exposure of cyclophosphamide. Both drugs
are metabolised in the liver, with ondansetron having an onset time of 30 minutes and
cyclophosphamide having a half-life of 3–12 hours, excreted through urine. Management
strategies for this combination include allowing a 1–2 hour gap between administrations
or considering safer antiemetic options, such as palonosetron (Drug.com, 2023; Koni et al.,
2022; Ramasubbu et al., 2021).
The potential interaction between oxaliplatin and ondansetron is classified as moderate in
severity, with a pharmacodynamic interaction type that has an additive effect, increasing
the risk of irregular heart rhythms, which could potentially lead to death (Drug.com, 2023;
Williamson & Polwart, 2016). Management strategies include closely monitoring the QT
interval via electrocardiogram (ECG). Patients should be advised to seek immediate
medical attention if they experience dizziness or irregular heartbeats. To minimize the risk
of interaction, the ondansetron dose can be adjusted to 8 mg, or alternatives such as
granisetron or palonosetron, other drugs in the 5-HT3 receptor antagonist class, can be
considered (de Lemos et al., 2019; Drug.com, 2023).
Based on Table 5, 41.08% of potential drug interactions were observed in combinations of
chemotherapy drugs. The most common interaction was between paclitaxel and
trastuzumab (15.78%), which involves an unknown interaction type with moderate
severity. This combination is frequently used as a first-line treatment in patients with
metastatic breast cancer. It may increase the serum concentration of trastuzumab while
decreasing the serum concentration of paclitaxel, which can increase the risk of
cardiotoxicity with long-term use of trastuzumab (Büyükköroǧlu et al., 2016). Management
strategies for this interaction include periodic monitoring of the patient's heart function via
ECG. Patients should also be advised to consult their doctor immediately if they experience
symptoms such as chest pain, nausea, sweating, coughing, or wheezing (Drug.com, 2023).
Another significant interaction was observed between doxorubicin and
cyclophosphamide, which is classified as a pharmacokinetic interaction with major severity
and risk level C. This interaction increases the risk of doxorubicin-induced cardiotoxicity,
which can lead to permanent heart damage or even death (Jamali et al., 2021; Kurniawati
et al., 2021). To manage this interaction, it is recommended to monitor heart function
before and during treatment, consider using a lower dose of cyclophosphamide compared
to doxorubicin, administer cyclophosphamide via infusion, and use liposomal doxorubicin
to reduce toxic effects (Atalay et al., 2014; Drug.com, 2023).

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Table 5. Category of Potential Drug Interactions
NO

Drug

Other Drug

Potentially Interaction
Total
%
Severity
Risk
Type
Level
Level
Interaction
Potential Chemotherapy Drug Interactions with Ancillary Drugs (46.47%)
1
Dexamethasone
Paclitaxel
Moderat*
PK
28
25%
2
Cyclophosphamide
Ondansetron
Minor**
B
Unknown
21
18.75%
3
Doxorubicin
Dexamethasone
Moderat*
PK
13
11.61%
4
Dexamethasone
Vincristine
Moderat*
PK
12
10.71%
5
Oxaliplatin
Ondansetron
Moderat*
PD
10
8.93%
6
Doxorubicin
Ondansetron
Moderat*
PD
8
7.14%
7
Carboplatin
Pantoprazole
Moderat*
PD
7
6.25%
8
Doxorubicin
Palonosetron
Moderat*
PD
6
5.36%
9
Dexamethasone
Irinotecan
Moderat*
PK
3
2.68%
10
Dexamethasone
Bortezomib
Minor **
B
PK
2
1.79%
11
Dexamethasone
Vinorelbine
Moderat*
PK
1
0.89%
12
Capecitabine
Omeprazole
Moderat**
C
Unknown
1
0.89%
Total
100%
Potential Interactions Between Chemotherapy Drugs (41.08%)
1
Paclitaxel
Trastuzumab
Moderat*
Unknow
15
15.78%
2
Cyclophosphamide
Doxorubicin
Mayor**
C
PK
13
13.68%
3
Doxorubicin
5-Fluorouracil
Moderat*
PD
13
13.68%
4
Cyclophosphamide
5-Fluorouracil
Moderat*
PD
13
13.68%
5
Doxorubicin
Paclitaxel
Mayor**
D
PK
11
11.57%
6
Carboplatin
Paclitaxel
Mayor**
D
Unknown
9
9.47%
7
Oxaliplatin
Capecitabine
Moderat*
PD
6
6.31%
8
Leucovorin
5-Fluorouracil
Mayor*
PD
5
5.26%
9
Doxorubicin
Trastuzumab
Mayor*
Unknown
3
3.15%
10
Carboplatin
Gemcitabine
Moderat*
Unknown
2
2.10%
11
Oxaliplatin
5-Fluorouracil
Moderat*
PD
2
2.10%
12
Tamoxifen
Goserelin
Moderat*
PK
2
2.10%
13
Doxorubicin
Carboplatin
Moderat**
D
PD
1
1.05%
Total
100%
Potential Interactions Between Ancillary Drugs (12.45%)
1
Ondansetron
Palonosetron
Moderat*
PD
10
33.33%
2
Dexamethasone
Alprazolam
Minor*
PD
4
13.13%
3
Dexamethasone
Celecoxib
Moderat*
PD
3
10.10%
4
Dexamethasone
Oxycodon
Mayor*
PD
2
6.67%
5
Diphenhydramine
Oxycodon
Mayor**
D
PD
2
6.67%
6
Ondansetron
Oxycodon
Moderat*
PD
1
3.33%
7
Dexamethasone
Rivaroxaban
Moderat*
PK
1
3.33%
8
Dexamethasone
Meloxicam
Moderat**
C
PD
1
3.33%
9
Diphenhydramine
Alprazolam
Moderat**
C
PD
1
3.33%
10
Diphenhydramine
Metoclorpramide
Moderat**
C
PD
1
3.33%
11
Diphenhydramine
Atropine sulfate
Moderat**
C
PD
1
3.33%
12
Diphenhydramine
Amitriptyline
Moderat**
C
PD
1
3.33%
13
Amitriptyline
Morfine
Mayor**
D
PD
1
3.33%
14
Cimetidine
Alprazolam
Moderat**
C
PK
1
3.33%
Total
100%
*drug.com; **Lexicomp; PK= Pharmacokinetics; PD= Pharmacodynamics (Drug.com. 2023; Lexicom. 2023)

A potential interaction was also found between supporting drugs, specifically
ondansetron and palonosetron, which accounted for 33.33% of interactions in this
category. This interaction is classified as pharmacodynamic with moderate severity. The
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combined use of these drugs can increase the risk of QT prolongation, which may lead to
arrhythmias and death (Novita & Destiani, 2019). Management strategies include
monitoring heart rhythm using ECG and ensuring that there is a time interval between the
administration of ondansetron and palonosetron. If possible, palonosetron alone should be
used, as it is a second-generation 5-HT3 receptor antagonist with stronger receptor affinity,
a longer elimination half-life (approximately 40 hours), and is more effective in controlling
nausea and vomiting during chemotherapy (Drug.com, 2023; Umar, 2018).
Table 6. Drug Interaction Management
No

Drug

Other
Interactions based on literature
Restriction Management based
Drug
on literature
Potential Chemotherapy Drug Interactions with Ancillary Drugs (46,47%)
1
Dexamethasone
Paclitax Co-administration with drugs that
Monitoring for decreased

el
induce CYP450 2C8 and/or 3A4
therapeutic response to
(dexamethasone) may reduce plasma
paclitaxel*
concentrations or blood levels of
Dexamethasone

Paclitaxel*.
administered no later than
30 minutes before paclitaxel
2
Cyclophosphamide Ondans Ondansetron may decrease the serum 
No intervention required*
etron
concentration of
Cyclophosphamide**.
3
Doxorubicin
Dexame Co-administration with drugs that
Monitoring for decreased

thasone induce CYP450 2C8 and/or 3A4
therapeutic response to
(dexamethasone) may reduce plasma
Doxorubicin*
concentrations or blood levels of
Dexamethasone

Doxorubicin*.
administered no later than 12 hours before Doxorubicin
4
Dexamethasone
Vincrist Decreases the effect of plasma
Dexamethasone is

ine
concentrations of Vincristine*
administered 1-2 hours
before vincristine*
5

Oxaliplatin

Ondans
etron

Increased risk of QT prolongation*





6

Doxorubicin

7

Carboplatin

Ondans
etron
Pantopr
azole

Increased risk of QT prolongation*



Use of proton pump inhibitors
(pantoprazole) may increase
hypomagnesia*





8

Doxorubicin

Palonos
etron

Increased risk of QT prolongation*



Regular monitoring of
cardiac function and rhythm
by performing an
electrocardiogram*
Dose adjustment is required,
and alternatives such as
Granisetron or palonosetron
may be substituted if possible
Regular monitoring of heart
function and rhythm*
Clinical and laboratory
monitoring of hematologic
and non-hematologic toxicity
is required*
Substitution with histamine
type-2 receptor antagonists
or the addition of sucralfate
is recommended if
hypomagnesia is indicated.
Regular monitoring of heart
function and rhythm*

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Study of Drug Interactions...
No

Drug

9

Dexamethasone

10

Dexamethasone

11

Dexamethasone

12

Capecitabine

Other
Drug
Irinotec
an

Interactions based on literature

Bortezo
mib
Vinorel
bine

Decreases serum concentration of
bortezomib**
Reduces the effects and blood levels
of vinorelbine*

Omepra
zole

Use of proton pump inhibitors
(omeprazole) may reduce the
therapeutic effect of capecitabine**

Reduced therapeutic effect and
blood levels of irinotecan*

Potential Interactions Between Chemotherapy Drugs (41,08%)
1
Paclitaxel
Trastuz Paclitaxel may enhance the
umab
cardiotoxic effects of trastuzumab

Restriction Management based
on literature
Monitoring the

pharmacological response of
irinotecan*
Dexamethasone is given 30

minutes before irinotecan
No intervention required*

Special care is needed if we use
the medicine together*
A change of medication is
recommended if possible*
Special monitoring of reduced

efficacy of capecitabine is
required**
Consideration of the use of

simethicone






2

Cyclophosphamide

Doxoru
bicin

Cyclophosphamide increases the
cardiotoxic effects of doxorubicin





3

Doxorubicin

5Fluorou
racil

Concurrent or sequential
administration may cause additive
toxicity, especially in the bone
marrow and gastrointestinal tract.*



4

Cyclophosphamide

5Fluorou
racil

Increased risk of side effects,
especially those affecting the bone
marrow and gastrointestinal tract*





5

Doxorubicin

Paclitax
el

Paclitaxel may increase
doxorubicin-induced
cardiovascular toxicity.**




Regular monitoring of the
patient's heart function by
conducting an
electrocardiogram*
Recommended that if the
patient experiences symptoms
of chest pain, immediately
consult a doctor.*
Monitor heart function**
Suggested a lower dose of
cyclophosphamide than
doxorubicin**
Suggested use of liposomal
doxorubicin to reduce
cardiotoxic risk**
Clinical monitoring as well as
laboratory examination of
haematologic and nonhaematologic toxicity and dose
adjustment of each drug*
Monitoring side effects with
clinical and laboratory
monitoring for hematologic
and non-hematologic toxicity*
Dose adjustment is required if
the patient develops fever,
chills, and diarrhea during
treatment.*
Monitoring of heart function**
Doxorubicin is given first, at
least 24 hours before
paclitaxel, and it is
recommended to add the
cytoprotective drug
dexrazoxane.

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Prasetya et al.
No

Drug

Other
Drug
Paclitax
el

Interactions based on literature

6

Carboplatin

7

Oxaliplatin

Capecit
abine

8

Leucovorin

5Fluorou
racil

Causes additive toxicity, especially
in the bone marrow and
gastrointestinal tract*
The combination of these drugs has
a synergistic effect, potentially
causing cardiotoxicity,
cardiomyopathy, heart failure,
diarrhoea, mucositis, and
myelosuppression.

9

Doxorubicin

Trastuz
umab

Trastuzumab induced doxorubicin,
resulting in increased cardiotoxic
effects such as cardiomyopathy*

10

Carboplatin

Gemcita
bine

Increased risk of side effects,
neurotoxicity, nephrotoxicity, and
ototoxicity*

11

Oxaliplatin

5Fluorou
racil

Increased neutropenia and anemia
incidence, peripheral neuropathy,
and hypersensitivity reactions

12

Tamoxifen

Gosereli
n

Increased risk of irregular heart
rhythms with potential death, and
electrolyte disturbances*

Increased risk of myelosuppressive
side effects from Paclitaxel **

Restriction Management based
on literature
Paclitaxel infusion is given first

before carboplatin; this order
of administration reduces
platelet toxicity**
If the patient develops

peripheral neuropathy, this
combination should be stopped
immediately to reduce further
damage
If co-administered, more frequent
monitoring of doses tailored to the
patient's needs is required*
Special monitoring of the dose,

it is recommended that the
dose of 5-FU is smaller than
leucovorin, and the potential
toxicity of 5-FU, such as
thrombocytopenia,
neutropenia, can be monitored
by conducting laboratory tests
*
The use of this drug

combination should not be
used or continued if the patient
has symptoms of
gastrointestinal toxicity until
the symptoms disappear*
Monitoring of blood drug levels

and heart function*
If possible, the use of

anthracycline therapy should
be avoided for up to 7 months
after discontinuation of
trastuzumab*
Use of Carboplatin infusion

after gemcitabine*
During the administration of

this combination, do not use
simultaneously with NSAID
drugs
Clinical and laboratory

monitoring of hematologic and
non-hematologic toxicities*
Calcium channel blocker (CCB)

drugs such as amlodipine are
recommended to reduce the
risk of oxaliplatin-induced
peripheral neuropathy
Recommended patients have their
electrolytes and heart function
checked by performing an ECG*

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Study of Drug Interactions...
No

Drug

13

Doxorubicin

Other
Drug
Carbopl
atin

Interactions based on literature
Increases the risk of additive
toxicity effects, especially in the
bone marrow and gastrointestinal
tract**

Potential Interactions Between Ancillary Drugs (12,45%)
1
Ondansetron
Palonos Increased cardiac rhythm*
etron

Restriction Management based
on literature
Clinical monitoring and

laboratory examination of
hematological, nonhematological toxicity, and
dose adjustment of each drug
**
Monitoring of side effects such

as nausea and vomiting **
Closely monitoring the
patient's heart rhythm by
performing an ECG *
Given a time lag in its use, for

example, palonosetron is given
as premedication while
ondansetron is given as postchemotherapy, or if possible,
use palonosetron alone
Recommended to allow about 1-2
hours between dexamethasone and
alprazolam*


2

Dexamethasone

Alprazo
lam

Co-administration with drugs that
induce CYP450 2C8 and/or 3A4
(dexamethasone) may reduce
plasma concentrations or blood
levels of Alprazolam*.
Increased effects of gastrointestinal
ulceration and bleeding*
Co-administration with drugs that
induce CYP450 2C8 and/or 3A4
(dexamethasone) may reduce
plasma concentrations or blood
levels of Oxycodon *.

3

Dexamethasone

4

Dexamethasone

Celecox
ib
Oxycod
on

5

Diphenhydramine

Oxycod
on

increased depressant effects on the
central nervous system**

6

Ondansetron

Oxycod
on

Increased risk of serotonin
syndrome*

7

Dexamethasone

Rivarox
aban

Dexamethasone may reduce blood
levels of rivaroxaban*

8

Dexamethasone

Meloxic
am

Increased effects of gastrointestinal
ulceration and bleeding*

Monitoring risk of side effects*
Monitoring pharmacologic
responses*
If used concomitantly, limit

the dose of the drug to the
minimum or as needed to
achieve the desired
therapeutic effect*
Monitoring depression of

respiration, central nervous
system**
If used concomitantly, dose

adjustment and dose titration
are required, especially at
treatment initiation**
Special monitoring for serotonin
syndrome symptoms during
treatment*


Dose adjustment and time interval
for administration are
recommended*
Monitoring side effects **

Recommended during the use

of meloxicam to add drugs that
can help protect the intestines
and stomach**

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Prasetya et al.
No

Drug

Other
Drug
Alprazo
lam

Interactions based on literature

9

Diphenhydramine

10

Diphenhydramine

Metoclo
rprami
de
Atropin
e
sulfate
Amitrip
tyline

Increased diastonic ripple and
depressant effects on the central
nervous system**
Increased additive toxic effect of
one of the drugs**

11

Diphenhydramine

12

Diphenhydramine

13

Amitriptyline

Morfine

Increased risk of serotonin
syndrome**

14

Cimetidine

Alprazo
lam

Cimetidine may prolong the effects
of alprazolam**

Increased risk to the central
nervous system due to sedative
effects**

Increased additive toxic effect of
one of the drugs**

Restriction Management based
on literature
If used together, dose

adjustment and dose titration
are required, especially at
treatment initiation**
Second-generation

antihistamines that do not
increase sedative effects are
recommended**
Monitoring depression of
respiration, central nervous
system**
Monitoring depression of
respiration, central nervous
system**
Monitoring depression of
respiration, central nervous
system**
Monitoring for depression of

respiration, central nervous
system**
Limit the dose and duration of

both drugs, and the initiation of
opioid dose reduction should
be considered
If used, consider reducing the
alprazolam dose by one-third or
dosing to twice daily

*drug.com **Lexicomp (Drug.com, 2023; Lexicom, 2023)

The use of chemotherapy and supportive drugs in cancer patients presents a high
potential for drug interactions. Special attention and monitoring are essential to prevent
Drug-Related Problems (DRPs). Studying potential drug interactions in cancer patients can
improve the quality of healthcare services, enhance therapeutic outcomes, and ultimately
increase the quality of life for patients while minimizing the risk of drug interactions. This
proactive approach ensures that drug efficacy is optimized and patient safety is maintained.
CONCLUSION
The results of this study indicate that chemotherapy drug combinations are more
commonly used in cancer patients, alongside additional supportive therapies, such as
antihistamines, corticosteroids, and 5-HT3 receptor antagonists, which are employed as
premedication and post-chemotherapy treatments. The most frequently encountered drug
interactions were pharmacodynamic interactions (50.42%), major severity interactions
(69.07%), and risk level C interactions (35.53%) at the X Cancer Center Polyclinic of RSU X
Denpasar. Recommended management strategies to address these potential drug
interactions include adjusting the timing of drug administration, considering alternative
drug combinations, and ensuring ongoing monitoring of drug interactions by pharmacists
or other healthcare professionals.

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Study of Drug Interactions...

ACKNOWLEDGMENT
The authors would like to express their deepest gratitude to the management and
staff of X Cancer Center at X General Hospital Denpasar for granting access and support
during the data collection process. We also extend our appreciation to the Health Research
Ethics Committee of Stikes Bina Usada Bali for providing ethical clearance and valuable
guidance for this research. Special thanks to all parties who contributed directly or
indirectly to the completion of this study.
AUTHOR CONTRIBUTION
AANPRP: Concepts or ideas; design; definition of intellectual content; literature search;
experimental studies; data analysis; manuscript preparation.
MD: literature search; experimental studies; data analysis.
PMDR: Manuscript editing; manuscript review.
NSLAS: Definition of intellectual content; literature search, manuscript preparation.
ETHICS APPROVAL
Ethical approval for this study was granted by the Health Research Ethics Committee of
Stikes Bina Usada Bali under ethical number 107/EA/KEPK-BUB-2024.
CONFLICT OF INTEREST
None to declare
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