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Assessment of Potential Drug–Drug Interactions in an Oncology Unit of a Tertiary Care Teaching Hospital

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2018; 39(04): 436-442

DOI: DOI: 10.4103/ijmpo.ijmpo_93_17

Abstract

Context: Drug interactions are more common in cancer patients because they consume several medicines such as hormonal substances, anticancer drugs, and adjuvant drugs to treat comorbidities. Objectives: To assess the pattern of potential drug–drug interactions (pDDIs) in an oncology unit of a tertiary care teaching hospital. Materials and Methods: A prospective observational study was carried out for 8 months (August 2016 to March 2017). Data on drugs were collected by reviewing the patients’ medical records. The drug interactions fact software version such as Micromedex electronic database system, drugs.com interaction checker, and Medscape multidrug interaction checker tool were used to identify and analyze the pattern of pDDIs. Results: A total of 180 patients were enrolled during the study period. Among them, 152 study patients had 84.44%-of pDDIs. Male predominance (64.4%) was noted over female (35.6%). According to the severity of classification of pDDIs, majority of them were moderate (63.1%) followed by major (26.1%) and minor (10.1%) interactions. The interactions that potentially cause QT interval prolongation and irregular heartbeat were the common outcomes of pDDIs. Conclusions: The incidence of pDDIs among cancer patients was 84.44%. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05%)] and other interacting pairs. To avoid harmful effects, screening of pDDIs should take place before administering the therapy.

Publication History

Article published online:
17 June 2021

© 2018. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Abstract

Context: Drug interactions are more common in cancer patients because they consume several medicines such as hormonal substances, anticancer drugs, and adjuvant drugs to treat comorbidities. Objectives: To assess the pattern of potential drug–drug interactions (pDDIs) in an oncology unit of a tertiary care teaching hospital. Materials and Methods: A prospective observational study was carried out for 8 months (August 2016 to March 2017). Data on drugs were collected by reviewing the patients’ medical records. The drug interactions fact software version such as Micromedex electronic database system, drugs.com interaction checker, and Medscape multidrug interaction checker tool were used to identify and analyze the pattern of pDDIs. Results: A total of 180 patients were enrolled during the study period. Among them, 152 study patients had 84.44%-of pDDIs. Male predominance (64.4%) was noted over female (35.6%). According to the severity of classification of pDDIs, majority of them were moderate (63.1%) followed by major (26.1%) and minor (10.1%) interactions. The interactions that potentially cause QT interval prolongation and irregular heartbeat were the common outcomes of pDDIs. Conclusions: The incidence of pDDIs among cancer patients was 84.44%. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05%)] and other interacting pairs. To avoid harmful effects, screening of pDDIs should take place before administering the therapy.

Introduction

Drug interactions are more common in cancer patients because they consume several medications such as hormonal substances, anticancer drugs, and adjuvant drugs to treat comorbidities.[1] [2] The risk of drug–drug interactions (DDIs) increases in elderly patients due to their increased age, physiological changes, and comorbidities.[3] Cytotoxic drugs have narrow therapeutic index, so increases or decreases in the cytotoxic activity result in toxic effect.[4]

Approximately, 60% of the patients undergoing treatment for cancer may develop at least one DDI, of which 30%-require medical intervention. QT prolongation, gastrointestinal (GI) toxicity, and central nervous system depression are the most common results of pharmacodynamic DDIs. Most of these potential drug–drug interactions (pDDIs) are left unnoticed or not given proper intervention due to the lack of healthy professional relationship between medical oncologists, pharmacists, and general practitioners.[5]

Before starting chemotherapy, it is necessary to check the pDDIs for the successful usage of drug therapy and to improve the quality of life of the patient. Clinical pharmacists require good knowledge in monitoring DDIs and should advise patients regarding the proper use of drugs. Hence, the present study was aimed to assess the patterns of pDDIs in the oncology unit of a tertiary care teaching hospital.

Materials and Methods

A prospective observational study was carried out for 8-month period (from August 2016 to March 2017) in the inpatient unit of oncology unit at Justice K.S. Hegde Charitable Hospital, Mangaluru. Before starting the study, the study protocol was approved by the Institutional Ethical Committee (Ref no: NIST. EC/EC/65/2016-2017). Either patients of gender with >18 years and diagnosed with solid tumor or hematological malignancy were included in the study. Patients who referred to oncology department for consultation, patients who are not willing to participate, pregnant and lactating women were excluded from the study.

The data were collected from patients’ treatment chart. Patient medication details were collected on the daily basis and recorded in the drug interactions’ documentation form. The pDDIs were those not observed in the patients but they give a signal for the detection of interactions. Micromedex electronic database system, drugs.com interaction checker, and Medscape multidrug interaction checker tool were used to identify the pattern of pDDIs.[6] [7] Micromedex contains a separate section on DDIs known as the Drug-REAX System, Denver, Colorado State, US. On entering the drugs one by one, the program lists the possible interactions and categorizes interactions according to their interaction effect, severity (major, moderate, and minor), onset (rapid and delayed), and documentation status (excellent, good and fair). Medscape and drugs.com contain a separate tool for detecting interactions known as the multidrug interaction checker tool. On entering the drugs one by one, the program lists the possible interactions and categorizes interactions according to their interaction effect, severity (major, moderate, and minor), and management. The required guidance to manage particular pDDI was provided to the physician by referring information provided in drug interaction tools.

Statistical analysis

Descriptive statistics were used to describe the demographic characteristic of patients, cancer type, treatment, comorbidities, number of drugs prescribed per patient, and classification of drug interactions. Data analysis was carried out using the Statistical Package for Social Studies (SPSS) version 16 (SPSS Inc., South Asia, Bengaluru).

Results

A total of 180 patients were included during the study period. Among them, 152 study patients had 84.44% of pDDIs. Male predominance (64.4%) was noted over female (35.6%). The mean age of the study population was 53.6 ± 12.4 years. Most of the patients were in the age group of 50–59 years (33.3%) followed by 60–69 years (23.9%). Majority of the patients had no family history of cancer (81.7%) and there was no history of comorbidities (83.8%). Hypertension [11 (7.2%)] was found to be the most common comorbidity observed in cancer patients with pDDIs followed by diabetes mellitus 9 (5.9%).

Out of 180 patients, 18.3% of patients had a history of smoking followed by alcohol and tobacco usage. Majority of the patients were hospitalized for 1–9 days. The median duration of the hospital stay was found to be 9 days. Out of 180 patients, breast cancer [24 (15.7%)] with pDDIs was the most common cancer type in the study population. The median number of medications received by the study population was found to be eight per day. Most of the pDDIs were observed in patients who had undergone 6–10 cycles of chemotherapy [70 (67.3%)], followed by 11–15 cycles [26 (14.4%)]. Patient characteristics and statistical significance of the results are summarized in [Table 1].

Table 1

Demographics of the study population

Among anticancer agents that cause pDDIs, alkylating agent + corticosteroids [32 (21.05%)] were found to be the most common interacting group in cancer patients followed by corticosteroids + mitotic inhibitors [31 (20.3%)], alkylating + mitotic inhibitors [26 (17.1%)] and the other interacting groups are summarized in [Table 2]. Similarly, in supportive care agents, corticosteroids + aprepitant [34 (22.3%)] were found to be the common interacting pair in cancer patients followed by histamine H2 antagonist + analgesics, 19 (12.5%), and the other interacting groups are described in [Table 3].

Demographic details

Number of patients with pDDIs (n=152) (%)

Number of patients without pDDIs (n=28) (%)

Total number of patients (n=180) (%)

*Carcinoma of nasal cavity, carcinoma of pancrease, carcinoma of oropharynx, osteosarcoma, carcinoma of postcricoid colon, carcinoma of maxilla, carcinoma of anal, carcinoma of gall bladder, carcinoma of hepatocellular, fibrillary astrocytoma, carcinoma of pyriform fossa, plemorphic rhabdomyosarcoma, carcinoma of rectosigmoid colon, microinvassive squamous cell carcinoma, carcinoma of tonsil, carcinoma of voccal cord, carcinoma of supraglotis, carcinoma of tongue, spindle cell sarcoma, carcinoma of buccal mucosa. pDDIs – Potential drug-drug interactions; HTN – Hypertension

Gender

Male

101 (66.4)

15 (53.5)

116 (64.4)

Female

51 (33.6)

13 (46.4)

64 (35.6)

Age groups

18-29

6 (3.9)

2 (7.1)

8 (4.4)

30-39

17 (11.1)

1 (3.6)

18 (10)

40-49

29 (19)

6 (21.4)

35 (19.4)

50-59

51 (33.5)

9 (32.1)

60 (33.3)

60-69

38 (25)

5 (17.8)

43 (23.9)

70-79

10 (6.5)

3 (10.7)

13 (7.2)

>80

1 (0.6)

2 (7.1)

3 (1.7)

Comorbidities

HTN

11 (7.2)

2 (7.1)

13 (7.2)

Diabetes mellitus

9 (5.9)

1 (3.5)

10 (5.6)

Asthma

2 (1.3)

1 (3.5)

3 (1.7)

Epilepsy

3 (1.9)

2 (7.1)

3 (1.7)

Social habits

Smoking

30 (19.7)

3 (10.7)

33 (18.3)

Alcohol

22 (14.4)

2 (7.14)

24 (13.3)

Tobacco

18 (11.8)

1 (3.5)

19 (10.5)

Length of hospital stay

1-9

77 (42.8)

14 (7.8)

91 (50.6)

10-19

29 (16.1)

3 (1.6)

31 (17.2)

20-29

12 (6.7)

4 (2.2)

17 (9.4)

30-39

23 (12.8)

6 (3.3)

29 (16.1)

40-49

5 (2.8)

-

5 (2.8)

50-59

3 (1.6)

-

3 (1.6)

60-69

3 (1.6)

1 (0.6)

4 (2.2)

Solid malignancy

Breast

24 (15.7)

2 (7.1)

26 (14.4)

Lung

18 (11.8)

5 (17.8)

23 (12.7)

Buccal mucosa

15 (9.8)

4 (14.2)

19 (10.5)

Esophagus

10 (6.5)

2 (7.1)

12 (6.6)

Stomach

13 (8.5)

3 (10.7)

16 (8.8)

Gynecologic

4 (2.6)

5 (17.8)

9 (5)

Gentio-urinary

3 (1.9)

1 (3.5)

4 (2.2)

Others*

47 (30.9)

2 (7.1)

49 (27.2)

Hemato-oncology

Malignant lymphoma

12 (7.8)

3 (10.7)

15 (8.3)

Leukemia

6 (3.9)

1 (3.5)

7 (3.8)

Number of medications

1-5

19 (12.5)

18 (64.2)

37 (20.6)

6-10

82 (53.9)

10 (35.7)

92 (51.1)

11-15

39 (25.6)

-

39 (21.7)

16-20

11 (7.2)

-

11 (6.1)

Table 2

Frequency of potential drug-drug interactions involving anticancer drugs (n=152)

Interacting anticancer drug pair

Number of patients (%)

NK1 – Neurokinin 1

Alkylating agents + corticosteroids

32 (21.05)

Corticosteroids + mitotic inhibitors

31 (20.3)

Alkylating agents + mitotic inhibitors

26 (17.1)

Alkylating agents + anthracycline

22 (14.5)

Alkylating agents + antimetabolite

20 (13.15)

Anthracycline + antiemetic

17 (11.2)

Anthracycline + corticosteroids

13 (8.6)

Alkylating agents + antiemetic

10 (6.6)

Mitotic Inhibitor + NK1 receptor antagonist

10 (6.6)

Anthracycline + NK1 receptor antagonist

7 (4.6)

Anthracycline + antimetabolite

6 (3.9)

Corticosteroids + antimetabolite

5 (3.2)

Histamine H2 antagonist + antimetabolite

4 (2.6)

Table 3

Frequency of potential drug-drug interactions involving supportive care drugs («=152)_

Out of 152 patients, 659 pDDIs were observed in the study. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05%)] the other interacting pairs are summarized in [Table 4] and [5]. QT interval prolongation [62 (40.1%)] was found to be the most common pDDI outcome in cancer patients.

Interacting supportive care drug pair

Number of patients (%)

PPIs – Proton pump inhibitors; NSAID – Nonsteroidal anti-inflammatory drug

Corticosteroids + aprepitant

34 (22.3)

Histamine H2 antagonist + analgesics

19 (12.5)

Antiemetic + opioids

17 (11.2)

Dopamine agonist + histamine H2 antagonist

17 (11.2)

Opioids + opioids

17 (11.2)

Dopamine agonist + histamine H2 antagonist

17 (11.2)

Tricyclic antidepressant + opioids

16 (10.5)

Antiemetic + antibiotic

10 (6.6)

Corticosteroids + anticonvulsant

8 (5.2)

Corticosteroids + antiemetic

7 (4.6)

Antihistamines + opioids

7 (4.6)

Dopamine agonist + antiemetic

7 (4.6)

PPIS + antifungal

6 (3.6)

Corticosteroids + laxative

6 (3.9)

Corticosteroids + antidysrhythmic

6 (3.9)

Corticosteroids + NSAID

5 (3.3)

NSAID + NSAID

5 (3.3)

Hypnotic + opioids

4 (2.6)

Hypnotic + hypnotic

4 (2.6)

Tricyclic antidepressant + antihistamines

4 (2.6)

Antiemetic + antifungal

4 (2.6)

Laxative + antiemetic

4 (2.6)

Opioids + anticonvulsant

4 (2.6)

Corticosteroids + biguanide

3 (1.9)

Corticosteroids + antifungal

3 (1.9)

Antibiotic + anticonvulsant

3 (1.9)

Bronchodilators + opioids

3 (1.9)

Tricyclic antidepressant + antiemetic

3 (1.9)

Antibiotic + laxative

3 (1.9)

Antifungal + opioids

3 (1.9)

Table 4

Interacting pair of anticancer drugs with outcome and severity (n=152)

PDIs involving anti-cancer drug

Outcome

Severity

Number of patients (%)

NK1 – Neurokinin 1; PDIs – Potential drug interactions

Alkylating agents + corticosteroids

Cisplatin + dexamethasone

Muscle pain

Moderate

32 (21.05)

Corticosteroids + mitotic inhibitors

Dexamethasone + paclitaxel

Reduces the blood level and effect of paclitaxel

Moderate

16 (10.5)

Dexamethasone + vincristine

Reduces the blood level and effect of vincristine

Moderate

15 (9.8)

Alkylating agents + mitotic inhibitors

Carboplatin/cisplatin + etoposide

Increases the effect of etoposide

Moderate

6 (3.9)

Cisplatin + paclitaxel

Anemia, bleeding problem and nerve damage

Major

3 (1.9)

Carboplatin + paclitaxel

Nerve damage

Major

13 (8.5)

Carboplatin + docetaxel

Nerve damage

Major

9 (5.9)

Cyclophosphamide + etoposide

Affect bone marrow function

Moderate

1 (0.6)

Alkylating agents + anthracycline

Cyclophosphamide + doxorubicin

Cardiomyopathy

Major

12 (3.2)

Carboplatin + doxorubicin

Increases doxorubicin exposure

Moderate

1 (0.6)

Ifosfamide + doxorubicin

Affect bone marrow function

Moderate

2 (1.3)

Cisplatin + epirubicin

Affect bone marrow function

Moderate

6 (3.9)

Oxaliplatin + epirubicin

Affect bone marrow function

Moderate

5 (3.2)

Alkylating agents + antimetabolite

Capecitabine + oxaliplatin

Affect bone marrow function

Moderate

3 (1.9)

Cisplatin + fluorouracil

Affect bone marrow function

Moderate

6 (3.9)

Cyclophosphamide + fluorouracil

Affect bone marrow function

Moderate

1 (0.6)

Gemcitabine + carboplatin

Affect bone marrow function

Moderate

2 (1.3)

Gemcitabine + oxaliplatin

Affect bone marrow function

Moderate

2 (1.3)

Carboplatin + pemetrexed

Affect bone marrow function

Moderate

6 (3.9)

Anthracycline + antiemetic

Affect bone marrow function

Moderate

Epirubicin/doxorubicin + palonosetron/ondansetron

Irregular heart beat

Moderate

17 (11.2)

Anthracycline + corticosteroids

Doxorubicin + dexamethasone

Decreases doxorubicin exposure

Major

13 (8.6)

Alkylating agents + antiemetic

Oxaliplatin + ondansetron

Irregular heart beat

Moderate

1 (0.6)

Oxaliplatin + palonosetron

Irregular heart beat

Moderate

4 (2.6)

Cyclophosphamide + ondansetron

Decreased cyclophosphamide systemic exposure

Moderate

3 (1.9)

Ifosfamide + aprepitant

Increases the blood levels and effect of ifosfamide

Moderate

1 (0.6)

Mitotic inhibitors + NK1 receptor antagonist

Docetaxel + aprepitant

Increases docetaxel exposure and toxicity

Major

3 (1.9)

Paclitaxel + aprepitant

Decreases blood level and effect of paclitaxel

Moderate

4 (2.6)

Aprepitant + etoposide

Increases blood level and effect of etoposide

Moderate

6 (3.9)

Vincristine + aprepitant

Increases blood level and effect of vincristine

Moderate

3 (1.9)

Anthracycline + NK1 receptor antagonist

Doxorubicin + aprepitant

Increases doxorubicin exposure

Major

7 (4.6)

Anthracycline + antimetabolite

Fluorouracil + epirubicin

Affect bone marrow function

Moderate

5 (3.2)

Fluorouracil + doxorubicin

Affect bone marrow function

Moderate

1 (0.6)

Corticosteroids + antimetabolite

Dexamethasone + methotrexate

Increases blood level

Moderate

5 (3.2)

Histamine H2 antagonist + antimetabolite

Ranitidine + pemetrexed

Increased blood level and effect of pemetrexed

Moderate

4 (2.6)

Table 5

Interacting pair of supportive care drugs with outcome and severity (n=152)

According to the severity of drug interactions, 416 (63.1%) of pDDIs were moderate followed by major [172 (26.1%)] and minor [67 (10.1%)]. Among the 659 interactions, 563 (85.4%) of pDDIs did not specify their onset [23 (3.4%)] were delayed onset, and 73 (11%) were rapid onset. The documentation levels of significance of pDDIs were fair [556 (84.3%)] followed by good [66 (10%)] and rapid [37 (5.6%)].

Discussion

Drug–drug interactions (DDIs) occur when one drug increases or decreases the efficacy of another drug, when both are administered together. When the interaction causes an increase in the effect of one or both of the drugs, that interaction is called synergistic effect. The opposite effect to synergetic effect is termed antagonism.[8]

The current study analyzed the pattern of pDDIs and their assessment among cancer patients. In this study, it was noticed that male (64.4%) patients constituted a major proportion of the study population than females (35.6%). Similar result was shown in the study conducted by Leeuwen et al.[9] where it was reported that males (55%) were higher than females (45%). However, contradictory results were shown in the study conducted by Ussai et al.,[10] in which female (69%) patients constituted the major proportion of the study population than male patients (31%).

Majority of the pDDIs were seen in patients in the age group of 50–59 years (33.5%) in our study. The study conducted by Riechelmann et al.[11] showed the similar results, where the drug interactions were common in the age group of 58 years. Our study results are in contrast to the study conducted by Ko et al.,[12] in which the maximum number of drug interactions in the age group was >65 years. This may be because organ dysfunction and comorbid conditions are more likely to be associated with older age. This further increases their risk for developing pDDIs.

In the present study, the most common tumor was found to be breast cancer (14.4%). A comparable result was shown in the study conducted by van Leeuwen et al.,[13] where it was found to be 17.2%. However, Mouzon et al.[14] concluded that higher incidence was observed with gastrointestinal cancer (27.9%). These findings were contradictory to the current study results.

The median number of medications received per patient in the present study was found to be 8 (range 1–21). A comparable result of median value of 9 in the range of 2–22 drugs was observed in the study conducted by van Leeuwen et al.[13] However, comparatively lesser median value of 5 was reported by Riechelmann et al.,[11] making it not comparable with the present study results.

In this study, the most frequently prescribed anticancer agents were cisplatin (14.5%) and docetaxel (1.9%). The study results were comparable to the conducted by Mouzon et al.,[14] where it was found to be cisplatin (22.1%) and docetaxel (13%).

In the current study, cisplatin [49 (32.2%)] was the most frequently drug involved in pDDIs. A comparable result was found in the study conducted by Mouzon et al.,[14] where it was found that cisplatin (22.1%) was the most frequently involved anticancer drug in pDDIs.

Another important finding in the study was the incidence of pDDIs that may result in adverse events which include QT interval prolongation (40.1%) and GI toxicity (9.2%). A comparable result was found in the study conducted by Leeuwen et al.,[9] where it was found to be QT interval prolongation (16.1%) and GI toxicity (11.2%).

In the present study, pain related to the cancer was treated with nonsteroidal anti-inflammatory drugs and opioids. These findings were consistent with the study conducted by Espinosa et al.[15] and van Leeuwen et al.[13]

The incidence of pDDIs in our hospital during the study period was 84.4%. Contradictory results were shown in the study conducted by Riechelmann et al.,[11] where it was reported to be 31.34%. This is due to that the patients involved in the study had more comorbidities; therefore, a large number of drugs were administered.

According to the severity of pDDIs, the study showed that 63.1% were moderate followed by major (26.1%) and minor interactions (10.1%). These findings were comparable to the study conducted by Leeuwen et al.,[9] where it was reported that most of the interactions were major (33%) followed by moderate (60.3%) and minor (6%).

Conclusion

The present study shows that cancer patients are at a high risk of pDDIs. The incidence of pDDIs among cancer patients was 84.44%. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05)] and other interacting pairs. According to the severity of classification of pDDIs, majority of them were moderate (63.1%) followed by major (26.1%) and minor (10.1%) interactions. QT interval prolongation (40.1%) and irregular heartbeat (24.3%) were the most common outcomes of the pDDIs in cancer patients. To avoid harmful effects, screening of pDDIs should take place before administering the therapy. The physician and pharmacist must collaborate for the early detection and prevention of DDIs and their related harmful effects. Screening of pDDIs should take place before starting the therapy to avoid potential drug interactions. Clinical pharmacist in health-care team has a certain role in detecting interactions and making recommendations, to reduce medication-related problem and effective drug therapy to improve the quality of life in these patients.

Conflict of Interest

There are no conflicts of interest.

References

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Address for correspondence

Dr. Uday Venkat Mateti
Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte University
Paneer, Deralakatte, Mangaluru - 575 018, Karnataka
India   

Publication History

Article published online:
17 June 2021

© 2018. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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PDIs involving supportive care drugs

Outcome

Severity

Number of patients (%)

PDIs – Potential drug interactions; PPIs – Proton pump inhibitors; NSAID – Nonsteroidal anti-inflammatory drug; CNS – Central nervous system; HTN – Hypertension; GI – Gastrointestinal

Corticosteroids + antiemetic

Dexamethasone + aprepitant

Increase systemic exposure to dexamethasone

Moderate

41 (26.9)

Histamine H2 antagonist+analgesics

Chlorpheniramine + tramadol

Increased risk of seizures

Major

19 (12.5)

Antiemetic + opioids

Ondansetron + tramadol

Reduced efficacy of tramadol

Moderate

17 (11.2)

Dopamine agonist + histamine H2 antagonist

Ranitidine + domperidone

Increased QT interval prolongation

Major

17 (11.2)

Opioids + opioids

Morphine + tramadol

Increased risk of CNS depression

Major

9 (5.9)

Morphine + morphine

Respiratory depression

Major

8 (5.2)

Tricyclic antidepressant + opioids

Amitriptyline + tramadol

Increased QT interval prolongation

Major

13 (8.6)

Amitriptyline + morphine

Respiratory depression

Major

3 (1.9)

Antibiotic + antiemetic

Azithromycin + ondansetron

Increased risk of QT interval prolongation

Major

9 (5.9)

Ciprofloxacin + ondansetron

Increased risk of QT interval prolongation

Major

1 (0.6)

Corticosteroids + anticonvulsant

Dexamethasone + phenytoin

Decreased dexamethasone effectiveness

Moderate

8 (5.2)

Corticosteroids + antiemetic

Dexamethasone + ondansetron

Decreases the effect of ondansetron

Moderate

7(4.6)

Antihistamines + opioids

Diphenhydramine + tramadol

Increased risk of CNS depression

Major

7 (4.6)

Dopamine agonist + antiemetic

Domperidone + ondansetron

Increased risk of QT interval prolongation

Major

7 (4.6)

Antifungal + PPIs

Fluconazole + pantoprazole

Increased concentration of CYP2C19

Moderate

6 (3.6)

Corticosteroids + laxative

Dexamethasone + magnesium hydroxide/lactulose

Dehydration and hypokalemia

Moderate

6 (3.9)

Corticosteroids + NSAID

Dexamethasone + diclofenac

Increases GI bleeding

Major

3 (1.9)

Dexamethasone + mefenamic acid

Increases GI bleeding

Major

2 (1.3)

NSAID + NSAID

Mefenamic acid + diclofenac

Increases GI bleeding

Major

5 (3.3)

Hypnotic + opioids

Zolpidem + tramadol

Increased risk of CNS depression

Major

4 (2.6)

Hypnotic + hypnotic

Zolpidem + zopiclone

Increased risk of CNS depression

Major

4 (2.6)

Tricyclic antidepressant + antihistamines

Amitriptyline + chlorpheniramine

HTN, tachycardia and cardiac arrhythmia

Major

2 (1.3)

Amitriptyline + diphenhydramine

Dry mouth, blurred, vision and drowsiness

Moderate

2 (1.3)

Antiemetic + antifungal

Fluconazole + ondansetron

Increased risk of QT interval prolongation

Major

4 (2.6)

Laxative + antiemetic

Magnesium sulfate + ondansetron

Irregular heart beat

Moderate

4 (2.6)

Opioids + anticonvulsant

Phenytoin + morphine/tramadol

Dizziness, confusion and drowsiness

Moderate

4 (2.6)

Corticosteroids + biguanide

Dexamethasone + metformin

Reduces the effectiveness of metformin

Moderate

3 (1.9)

Corticosteroids + antifungal

Dexamethasone + fluconazole

Increased glucocorticoid exposure and risk for toxicity

Moderate

3 (1.9)

Antibiotic + anticonvulsant

Sulfamethoxazole trimethoprim + phenytoin

Increased phenytoin toxicity

Moderate

3 (1.9)

Bronchodilators + opioids

Theophylline + tramadol

Increases the risk of seizure

Major

3 (1.9)

Tricyclic antidepressant + antiemetic

Amitriptyline + ondansetron

Increased risk of QT interval prolongation

Major

3 (1.9)

Antibiotic + laxative

Azithromycin + aluminum hydroxide

Decreases the effect of azithromycin

Moderate

2 (1.3)

Levofloxacin + magnesium hydroxide

Decreases the effect of levofloxacin

Moderate

1 (0.6)

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