Skip to main content

Advertisement

SpringerLink
Log in

Nationwide prevalence of potential drug-drug interactions associated with non-anticancer agents in patients on oral anticancer agents in South Korea

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

We analyzed the prevalence and severity of potential drug-drug interactions (PDDIs) in Korean patients receiving oral anticancer agents (OAAs) during two different periods.

Methods

A cross-sectional study was conducted using the national insurance reimbursement database. The subjects were adult outpatients diagnosed with cancer and prescribed OAAs at least once in 2010 or 2014. PDDIs were identified using a database and the PDDI severity was categorized as category X (contraindications) or D (consideration of therapy modification). The associated factors for the occurrence of PDDIs were also analyzed.

Results

Among the 118,258 patients prescribed OAAs in 2014, approximately 59% were middle-aged, and approximately half were diagnosed with breast cancer. The number of comorbidities increased over time, and majority were diagnosed with gastrointestinal disorders, hyperlipidemia, and psychonervous disorders. The PDDIs due to protein kinase inhibitors (PKIs) with gastrointestinal/metabolic and neurological drugs increased 3.1- and 4.9-fold, respectively, over the 5 years, and 24.0% of the PDDIs fell into category X. Tamoxifen, the most commonly prescribed OAAs, caused the PDDIs with antidepressants through QTc prolongation or pharmacokinetic interaction. The PKIs prescription, cancer type like breast or hematologic cancer, and number of comorbidities or co-prescribing drugs were independently associated with the occurrence of PDDIs.

Conclusions

The risk of PDDIs in patients receiving OAAs increases, particularly with the concomitant use of PKIs with gastrointestinal or psychiatric drugs and endocrine agents with antidepressants. Considering the potential risk of chronic concomitant use of these drug classes in outpatients, healthcare professionals should be made aware of the potential interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. van Leeuwen RW, Swart EL, Boven E, Boom FA, Schuitenmaker MG, Hugtenburg JG (2011) Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method. Ann Oncol 22:2334–2341. https://doi.org/10.1093/annonc/mdq761

    Article  PubMed  Google Scholar 

  2. Dechanont S, Maphanta S, Butthum B, Kongkaew C (2014) Hospital admissions/visits associated with drug-drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 23:489–497. https://doi.org/10.1002/pds.3592

    Article  PubMed  Google Scholar 

  3. Huang SM, Strong JM, Zhang L, Reynolds KS, Nallani S, Temple R, Abraham S, Habet SA, Baweja RK, Burckart GJ, Chung S, Colangelo P, Frucht D, Green MD, Hepp P, Karnaukhova E, Ko HS, Lee JI, Marroum PJ, Norden JM, Qiu W, Rahman A, Sobel S, Stifano T, Thummel K, Wei XX, Yasuda S, Zheng JH, Zhao H, Lesko LJ (2008) New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 48:662–670. https://doi.org/10.1177/0091270007312153

    Article  CAS  PubMed  Google Scholar 

  4. Lees J, Chan A (2011) Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol 12:1249–1257. https://doi.org/10.1016/s1470-2045(11)70040-7

    Article  PubMed  Google Scholar 

  5. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG (2014) Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 15:e315–e326. https://doi.org/10.1016/s1470-2045(13)70579-5

    Article  PubMed  Google Scholar 

  6. van Leeuwen RW, Brundel DH, Neef C, van Gelder T, Mathijssen RH, Burger DM, Jansman FG (2013) Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer 108:1071–1078. https://doi.org/10.1038/bjc.2013.48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hadjibabaie M, Badri S, Ataei S, Moslehi AH, Karimzadeh I, Ghavamzadeh A (2013) Potential drug-drug interactions at a referral hematology-oncology ward in Iran: a cross-sectional study. Cancer Chemother Pharmacol 71:1619–1627. https://doi.org/10.1007/s00280-013-2162-5

    Article  CAS  PubMed  Google Scholar 

  8. Jung H, Song YM (2012) Analysis of the development and marketing authorization of anticancer drugs in South Korea. Korea Food and Drug Administration. https://www.bioin.or.kr/board.do?num=226682&cmd=view&bid=system&cPage=30&cate1=all&cate2=all2.

  9. Ko Y, Tan SL, Chan A, Wong YP, Yong WP, Ng RC, Lim SW, Salim A (2012) Prevalence of the coprescription of clinically important interacting drug combinations involving oral anticancer agents in Singapore: a retrospective database study. Clin Ther 34:1696–1704. https://doi.org/10.1016/j.clinthera.2012.06.025

    Article  PubMed  Google Scholar 

  10. Solomon JM, Ajewole VB, Schneider AM, Sharma M, Bernicker EH (2018) Evaluation of the prescribing patterns, adverse effects, and drug interactions of oral chemotherapy agents in an outpatient cancer center. J Oncol Pharm Pract. https://doi.org/10.1177/1078155218798150

  11. Phillips JL, Currow DC (2010) Cancer as a chronic disease. Collegian 17:47–50

    Article  Google Scholar 

  12. Jansman FG, Reyners AK, van Roon EN, Smorenburg CH, Helgason HH, le Comte M, Wensveen BM, van den Tweel A, de Blois M, Kwee W, Kerremans AL, Brouwers JR, Scientific Institute for Dutch Pharmacists (WINAp), Dutch Society for Medical Oncology (NVMO), Dutch Society of Clinical Pharmacology and Biopharmacy (NVKF&B) (2011) Consensus-based evaluation of clinical significance and management of anticancer drug interactions. Clin Ther 33:305–314. https://doi.org/10.1016/j.clinthera.2011.01.022

    Article  CAS  PubMed  Google Scholar 

  13. Lee SM, Lee SO, Kim DS (2017) Physicians’ and pharmacists’ perceptions on real-time drug utilization review system: a nationwide survey. Int J Qual Health Care 29:634–641. https://doi.org/10.1093/intqhc/mzx085

    Article  PubMed  Google Scholar 

  14. Health Insurance Review and Assessment Service (2018) Application method and criteria of medical care for medicines prescribed and administered to cancer patients (No. 2018–162, 2018.7.1.)

  15. Song YK, Han N, Kim MG, Chang HJ, Sohn HS, Ji E, Oh JM (2017) A national pharmacoepidemiological study of antibiotic use in Korean paediatric outpatients. Arch Dis Child 102:660–666. https://doi.org/10.1136/archdischild-2016-310981

    Article  PubMed  Google Scholar 

  16. Standard Korean Dictionary. National Institute of Korean Language. https://www.korean.go.kr/front_eng/main.do. Accessed 26 January 2019

  17. Korea Central Cancer Registry, National Cancer Center (2012) Annual report of cancer statistics in Korea in 2010. Ministry of Health and Welfar. http://ncc.re.kr/cancerStatsList.ncc?searchKey=total&sear hValue=&pageNum=1.

  18. Korea Central Cancer Registry, National Cancer Center (2016) Annual report of cancer statistics in Korea in 2014. Ministry of Health and Welfare. http://ncc.re.kr/cancerStatsList.ncc?searchKey=total&searchValue=&pageNum=1.

  19. Ministry of Food and Drug Safety (2015) Regulation on codes for classification of drugs and other products (Internal Rule No. 196)

  20. WHO Collaborating Centre for Drug Statistics Methodology (2019) ATC/DDD index 2019. Oslo, Norway https://www.whocc.no/atc_ddd_index.

    Google Scholar 

  21. KIMS Drug information center. KIMS Co., Ltd. http://www.kimsonline.co.kr/.

  22. Tobi H, Faber A, van den Berg PB, Drane JW, de Jong-van den Berg LT (2007) Studying co-medication patterns: the impact of definitions. Pharmacoepidemiol Drug Saf 16:405–411. https://doi.org/10.1002/pds.1304

    Article  PubMed  Google Scholar 

  23. National Comprehensive Cancer Network (2018) NCCN guidelines – NCCN guidelines for treatment of cancer by site. https://www.nccn.org/professionals/physician_gls/default.aspx.

  24. Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF (2014) Herb-drug interactions: challenges and opportunities for improved predictions. Drug Metab Dispos 42:301–317. https://doi.org/10.1124/dmd.113.055236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. National Comprehensive Cancer Network (2018) NCCN clinical practice guidelines in oncology - antiemesis. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf.

  26. Tatro DS (2016) Drug interaction facts™. Wolters Kluwer Health, St. Louis, MO

    Google Scholar 

  27. Micromedex® 2.0. Truven health analytics. http://www.micromedexsolutions.com. Accessed 26 January 2019

  28. Lexi-Interact®. Wolters Kluwer Clinical Drug Information, Inc. http://libproxy.cu.ac.kr/cec4f7d/_Lib_Proxy_Url/online.lexi.com/lco/action/interact. Accessed 26 January 2019

  29. Bossaer JB, Thomas CM (2017) Drug interaction database sensitivity with oral antineoplastics: an exploratory analysis. J Oncol Pract 13:e217–e222. https://doi.org/10.1200/jop.2016.016212

    Article  PubMed  Google Scholar 

  30. Woosley RL, Romero KA. QTdrugs list. AZCERT, Inc. http://www.Crediblemeds.org. Accessed e January 2019

  31. European Medicines Agency (2012) Guideline on the investigation of drug interactions. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions_en.pdf.

  32. Leong SPL, Shen Z-Z, Liu T-J, Agarwal G, Tajima T, Paik NS, Sandelin K, Derossis A, Cody H, Foulkes WD (2010) Is breast cancer the same disease in Asian and Western countries? World J Surg 34:2308–2324. https://doi.org/10.1007/s00268-010-0683-1

    Article  PubMed  PubMed Central  Google Scholar 

  33. National Cancer Information Center. National cancer center. https://www.cancer.go.kr.

  34. Eom BW, Jung KW, Won YJ, Yang H, Kim YW (2018) Trends in gastric cancer incidence according to the clinicopathological characteristics in Korea, 1999-2014. Cancer Res Treat 50:1343–1350. https://doi.org/10.4143/crt.2017.464

    Article  PubMed  PubMed Central  Google Scholar 

  35. Joseph T, DiPiro RLT, Yee GC et al (2017) Pharmacotherapy: a pathophysiologic approach, 10th edn. McGraw-Hill Education, New Yorke

    Google Scholar 

  36. National Health Insurance Service, Health Insurance Review & Assessment Service (2011) 2010 National health insurance statistical yearbook. https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA020045020000&brdScnBltNo=4&brdBltNo=2303&pageIndex=1.

  37. National Health Insurance Service, Health Insurance Review & Assessment Service (2015) 2014 National health insurance statistical yearbook. https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA020045020000&brdScnBltNo=4&brdBltNo=2307&pageIndex=1.

  38. Kim MG, Jeong CR, Kim HJ, Kim JH, Song YK, Kim KI, Ji E, Yoon SS, Koh Y, Cho YS, Kim IW, Oh JM (2018) Network analysis of drug-related problems in hospitalized patients with hematologic malignancies. Support Care Cancer 26:2737–2742. https://doi.org/10.1007/s00520-018-4106-4

    Article  PubMed  Google Scholar 

  39. Chu MP, Ghosh S, Chambers CR, Basappa N, Butts CA, Chu Q, Fenton D, Joy AA, Sangha R, Smylie M, Sawyer MB (2015) Gastric acid suppression is associated with decreased erlotinib efficacy in non-small-cell lung cancer. Clin Lung Cancer 16:33–39. https://doi.org/10.1016/j.cllc.2014.07.005

    Article  CAS  PubMed  Google Scholar 

  40. Hansten PD (2018) The underrated risks of tamoxifen drug interactions. Eur J Drug Metab Pharmacokinet 43:495–508. https://doi.org/10.1007/s13318-018-0475-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fung K, Imeson J, Cusano F (2018) The clinical significance of QT prolongation associated with tamoxifen: a review of the literature. J Oncol Pharm Pract 24:525–530. https://doi.org/10.1177/1078155217720006

    Article  CAS  PubMed  Google Scholar 

  42. Heo J, Chun M, Oh YT, Noh OK, Kim L (2017) Psychiatric comorbidities among breast cancer survivors in South Korea: a nationwide population-based study. Breast Cancer Res Treat 162:151–158. https://doi.org/10.1007/s10549-016-4097-0

    Article  PubMed  Google Scholar 

  43. Lee J, Noh Y, Lee S (2018) Evaluation of preventable adverse drug reactions by implementation of the nationwide network of prospective drug utilization review program in Korea. PLoS One 13:e0195434. https://doi.org/10.1371/journal.pone.0195434

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ministry of Food and Drug Safety (2018) Regulations on the designation of active ingredients prohibited co-prescription, etc. (Internal rule No. 2018–88)

Download references

Acknowledgments

This study was conducted using data provided by the Korean Health Insurance Review and Assessment Service (HIRA). The authors greatly appreciate the HIRA for providing access to its claims database for this study.

Funding

This work was supported by research grants from Daegu Catholic University in 2018 (No. 20181188).

Author information

Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea

    Yun-Kyoung Song & Jung Mi Oh

  2. College of Pharmacy, Daegu Catholic University, Hayang-ro 13-13, Hayang-eup, Gyeongsan-si, Gyeongbuk, 38430, Republic of Korea

    Yun-Kyoung Song

Authors
  1. Yun-Kyoung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung Mi Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jung Mi Oh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 807 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, YK., Oh, J.M. Nationwide prevalence of potential drug-drug interactions associated with non-anticancer agents in patients on oral anticancer agents in South Korea. Support Care Cancer 28, 3711–3720 (2020). https://doi.org/10.1007/s00520-019-05221-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-019-05221-1

Keywords

Search

Navigation