Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Potential Drug-Drug Interactions Between Anti-Cancer Drugs and Other Medications in Lung Cancer Patients: A Retrospective Study

Author(s): Rosella Ayesha Pinto, Mahadev Rao*, Arpita Roy, Levin Thomas, Karthik S. Udupa and Vasudeva Guddattu

Volume 18, Issue 2, 2023

Published on: 26 August, 2022

Page: [175 - 189] Pages: 15

DOI: 10.2174/1574886317666220324100356

Price: $65

Abstract

Background: Cancer patients are more vulnerable to developing drug-drug interactions as multiple medications are administered concomitantly with cytotoxic agents to treat the underlying comorbidities. These drug-drug interactions often receive less medical attention and consequently are associated with adverse clinical outcomes.

Objective: We intended to comprehensively characterize the drug-drug interactions among anticancer drugs and other concomitantly prescribed drugs in hospitalized lung cancer patients.

Methods: A retrospective, observational, single-centre study was conducted on lung cancer inpatients from the medical records department of Kasturba Hospital, Manipal, India. Drug-drug interactions were identified using the drug interaction checkers of two drug information databases, Micromedex and Epocrates. These drug-drug interactions were categorized based on the source from which they were identified, mechanism, severity/significance, adverse consequences, and management strategies required.

Results: Among 196 patients, 555 drug-drug interactions were identified in 185 patients using Micromedex and Epocrates. Based on the mechanism of action, 74% and 22% of the drug-drug interactions were classified as pharmacodynamic and pharmacokinetic respectively. 112 drug-drug interactions were recorded from Micromedex alone, while 549 interactions were found using Epocrates. The oral chemotherapeutic drug gefitinib was found to be associated with the highest number of drug-drug interactions.

Conclusion: Drug-drug interactions were highly prevalent among hospitalized lung cancer patients. Structured screening and monitoring for these potentially clinically relevant drug-drug interactions by oncologists in collaboration with clinical pharmacists should be carried out prior to initiation and during anticancer treatment to prevent adverse clinical outcomes.

Keywords: Lung cancer, drug-drug interactions, pharmacokinetics, pharmacodynamics, anti-cancer drugs, anti-tumour agents.

Graphical Abstract
[1]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: A clinical perspective. Lancet Oncol 2014; 15(8): e315-26.
[http://dx.doi.org/10.1016/S1470-2045(13)70579-5] [PMID: 24988935]
[3]
Xu Z-Y, Li J-L. Comparative review of drug-drug interactions with epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer. OncoTargets Ther 2019; 12: 5467-84.
[http://dx.doi.org/10.2147/OTT.S194870] [PMID: 31371986]
[4]
Kannan G, Anitha R, Rani VN, et al. A study of drug-drug interactions in cancer patients of a south Indian tertiary care teaching hospital. Postgrad Med J 2011; 57(3): 206-10.
[http://dx.doi.org/10.4103/0022-3859.85207] [PMID: 21941058]
[5]
van Leeuwen RW, Brundel DH, Neef C, et al. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer 2013; 108(5): 1071-8.
[http://dx.doi.org/10.1038/bjc.2013.48] [PMID: 23412102]
[6]
Riechelmann RP, Moreira F, Smaletz O, Saad ED. Potential for drug interactions in hospitalized cancer patients. Cancer Chemother Pharmacol 2005; 56(3): 286-90.
[http://dx.doi.org/10.1007/s00280-004-0998-4] [PMID: 15731916]
[7]
Voll ML, Yap KD, Terpstra WE, Crul M. Potential drug-drug interactions between anti-cancer agents and community pharmacy dispensed drugs. Pharm World Sci 2010; 32(5): 575-80.
[http://dx.doi.org/10.1007/s11096-010-9410-0] [PMID: 20645002]
[8]
Baburaj G, Thomas L, Rao M. Potential drug interactions of repurposed COVID-19 drugs with lung cancer pharmacotherapies. Arch Med Res 2021; 52(3): 261-9.
[http://dx.doi.org/10.1016/j.arcmed.2020.11.006] [PMID: 33257051]
[9]
Rashdan S, Yang H, Le T, Selby C, Gerber DE, Alvarez CA. Prevalence and significance of potential pharmacokinetic drug-drug interactions among patients with lung cancer: Implications for clinical trials. Clin Drug Investig 2021; 41(2): 161-7.
[http://dx.doi.org/10.1007/s40261-020-00994-4] [PMID: 33417195]
[10]
Occhipinti M, Brambilla M, Galli G, et al. Evaluation of drug-drug interactions in EGFR-mutated non-small-cell lung cancer patients during treatment with tyrosine-kinase inhibitors. J Pers Med 2021; 11(5): 424.
[http://dx.doi.org/10.3390/jpm11050424] [PMID: 34069851]
[11]
Hakozaki T, Matsuo T, Shimizu A, Ishihara Y, Hosomi Y. Polypharmacy among older advanced lung cancer patients taking EGFR tyrosine kinase inhibitors. J Geriatr Oncol 2021; 12(1): 64-71.
[http://dx.doi.org/10.1016/j.jgo.2020.09.011] [PMID: 32952094]
[12]
Jorgensen T, Herrstedt J, Friis S, Hallas J. Polypharmacy and drug use in elderly Danish cancer patients during 1996 to 2006. J Geriatr Oncol 2012; 3(1): 33-40.
[http://dx.doi.org/10.1016/j.jgo.2011.09.001]
[13]
Hoemme A, Barth H, Haschke M, et al. Prognostic impact of polypharmacy and drug interactions in patients with advanced cancer. Cancer Chemother Pharmacol 2019; 83(4): 763-74.
[http://dx.doi.org/10.1007/s00280-019-03783-9] [PMID: 30684020]
[14]
Song X, Varker H, Eichelbaum M, et al. Treatment of lung cancer patients and concomitant use of drugs interacting with cytochrome P450 isoenzymes. Lung Cancer 2011; 74(1): 103-11.
[http://dx.doi.org/10.1016/j.lungcan.2011.01.016] [PMID: 21382644]
[15]
Yang C-Y, Yang JC-H, Yang P-C. Precision management of advanced non–small cell lung cancer. Annu Rev Med 2020; 71: 117-36.
[http://dx.doi.org/10.1146/annurev-med-051718-013524] [PMID: 31986082]
[16]
Bechtold B, Clarke J. Multi-factorial pharmacokinetic interactions: Unraveling complexities in precision drug therapy. Expert Opin Drug Metab Toxicol 2021; 17(4): 397-412.
[http://dx.doi.org/10.1080/17425255.2021.1867105] [PMID: 33339463]
[17]
Mathur P, Sathishkumar K, Chaturvedi M, et al. ICMR-NCDIR-NCRP Investigator Group. Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Glob Oncol 2020; 6: 1063-75.
[http://dx.doi.org/10.1200/GO.20.00122] [PMID: 32673076]
[18]
Kongsholm GG, Nielsen AKT, Damkier P. Drug interaction databases in medical literature: transparency of ownership, funding, classification algorithms, level of documentation, and staff qualifications. A systematic review. Eur J Clin Pharmacol 2015; 71(11): 1397-402.
[http://dx.doi.org/10.1007/s00228-015-1943-7] [PMID: 26369536]
[19]
Popa MA, Wallace KJ, Brunello A, Extermann M, Balducci L. Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy. J Geriatr Oncol 2014; 5(3): 307-14.
[http://dx.doi.org/10.1016/j.jgo.2014.04.002] [PMID: 24821377]
[20]
Riechelmann RP, Zimmermann C, Chin SN, et al. Potential drug interactions in cancer patients receiving supportive care exclusively. J Pain Symptom Manage 2008; 35(5): 535-43.
[http://dx.doi.org/10.1016/j.jpainsymman.2007.06.009] [PMID: 18243638]
[21]
van Leeuwen RW, Swart EL, Boven E, Boom FA, Schuitenmaker MG, Hugtenburg JG. Potential drug interactions in cancer therapy: A prevalence study using an advanced screening method. Ann Oncol 2011; 22(10): 2334-41.
[http://dx.doi.org/10.1093/annonc/mdq761] [PMID: 21343376]
[22]
Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38(1): 41-57.
[http://dx.doi.org/10.2165/00003088-200038010-00003] [PMID: 10668858]
[23]
The US Food and drug administration. TARCEVA (Erlotinib) prescribing information. 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf (Accessed July 5, 2020).
[24]
Beijnen JH, Schellens JH. Drug interactions in oncology. Lancet Oncol 2004; 5(8): 489-96.
[http://dx.doi.org/10.1016/S1470-2045(04)01528-1] [PMID: 15288238]
[25]
The US food and drug administration. IRESSA (Gefitinib) prescribing information. 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206995s003lbl.pdf (accessed July 5, 2020).
[26]
Daggupati SJV, Saxena PUP, Kamath A, Chowta MN. Drug-drug interactions in patients undergoing chemoradiotherapy and the impact of an expert team intervention. Int J Clin Pharm 2020; 42(1): 132-40.
[http://dx.doi.org/10.1007/s11096-019-00949-6] [PMID: 31865596]
[27]
Fang Y-H, Yang Y-H, Hsieh M-J, Hung M-S, Lin Y-C. Concurrent proton-pump inhibitors increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment - a nationwide population-based study. Cancer Manag Res 2019; 11: 8539-46.
[http://dx.doi.org/10.2147/CMAR.S222278] [PMID: 31572008]
[28]
Sharma M, Holmes HM, Mehta HB, et al. The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer. Cancer 2019; 125(7): 1155-62.
[http://dx.doi.org/10.1002/cncr.31917] [PMID: 30605231]
[29]
Chen Y-M, Lai C-H, Chang H-C, et al. Antacid use and de novo brain metastases in patients with epidermal growth factor receptor-mutant non-small cell lung cancer who were treated using first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitors. PLoS One 2016; 11(2): e0149722.
[http://dx.doi.org/10.1371/journal.pone.0149722] [PMID: 26894507]
[30]
Indini A, Petrelli F, Tomasello G, et al. Impact of use of gastric-acid suppressants and oral anti-cancer agents on survival outcomes: A systematic review and meta-analysis. Cancers (Basel) 2020; 12(4): 998.
[http://dx.doi.org/10.3390/cancers12040998] [PMID: 32325628]
[31]
van Leeuwen RW, Peric R, Hussaarts KG, et al. Influence of the acidic beverage cola on the absorption of erlotinib in patients with non–small-cell lung cancer. J Clin Oncol 2016; 34(12): 1309-14.
[http://dx.doi.org/10.1200/JCO.2015.65.2560] [PMID: 26858332]
[32]
Sasu-Tenkoramaa J, Fudin J. Drug interactions in cancer patients requiring concomitant chemotherapy and analgesics. Pract Pain Manag 2013; 13(4): 50-64.
[33]
Mouzon A, Kerger J, D’Hondt L, Spinewine A. Potential interactions with anticancer agents: A cross-sectional study. Chemotherapy 2013; 59(2): 85-92.
[http://dx.doi.org/10.1159/000351133] [PMID: 23881290]
[34]
Kafetz K. Renal impairment in the elderly: A review. J R Soc Med 1983; 76(5): 398-401.
[http://dx.doi.org/10.1177/014107688307600514] [PMID: 6191032]
[35]
De Jager R, Longeval E, Klastersky J. High-dose cisplatin with fluid and mannitol-induced diuresis in advanced lung cancer: A phase II clinical trial of the EORTC Lung Cancer Working Party (Belgium). Cancer Treat Rep 1980; 64(12): 1341-6.
[PMID: 6258791]
[36]
Muraki K, Koyama R, Honma Y, et al. Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer. J Thorac Dis 2012; 4(6): 562-8.
[PMID: 23205279]
[37]
Rao KV, Faso A. Chemotherapy-induced nausea and vomiting: Optimizing prevention and management. Am Health Drug Benefits 2012; 5(4): 232-40.
[PMID: 24991322]
[38]
Duckett DR, Cameron MD. Metabolism considerations for kinase inhibitors in cancer treatment. Expert Opin Drug Metab Toxicol 2010; 6(10): 1175-93.
[http://dx.doi.org/10.1517/17425255.2010.506873] [PMID: 20684746]
[39]
van Erp NP, Gelderblom H, Guchelaar H-J. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 2009; 35(8): 692-706.
[http://dx.doi.org/10.1016/j.ctrv.2009.08.004] [PMID: 19733976]
[40]
Peters S, Zimmermann S, Adjei AA. Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: Comparative pharmacokinetics and drug-drug interactions. Cancer Treat Rev 2014; 40(8): 917-26.
[http://dx.doi.org/10.1016/j.ctrv.2014.06.010] [PMID: 25027951]
[41]
Gay C, Toulet D, Le Corre P. Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy. Hematol Oncol 2017; 35(3): 259-80.
[http://dx.doi.org/10.1002/hon.2335] [PMID: 27925256]
[42]
Hamilton M, Wolf JL, Drolet DW, et al. The effect of rifampicin, a prototypical CYP3A4 inducer, on erlotinib pharmacokinetics in healthy subjects. Cancer Chemother Pharmacol 2014; 73(3): 613-21.
[http://dx.doi.org/10.1007/s00280-014-2390-3] [PMID: 24474302]
[43]
Deeken JF, Beumer JH, Anders NM, Wanjiku T, Rusnak M, Rudek MA. Preclinical assessment of the interactions between the antiretroviral drugs, ritonavir and efavirenz, and the tyrosine kinase inhibitor erlotinib. Cancer Chemother Pharmacol 2015; 76(4): 813-9.
[http://dx.doi.org/10.1007/s00280-015-2856-y] [PMID: 26330331]
[44]
Tang C, Lin JH, Lu AY. Metabolism-based drug-drug interactions: What determines individual variability in cytochrome P450 induction? Drug Metab Dispos 2005; 33(5): 603-13.
[http://dx.doi.org/10.1124/dmd.104.003236] [PMID: 15673596]
[45]
Tannenbaum C, Sheehan NL. Understanding and preventing drug-drug and drug-gene interactions. Expert Rev Clin Pharmacol 2014; 7(4): 533-44.
[http://dx.doi.org/10.1586/17512433.2014.910111] [PMID: 24745854]
[46]
Ma Y, Xin S, Huang M, et al. Determinants of Gefitinib toxicity in advanced Non-Small Cell Lung Cancer (NSCLC): A pharmacogenomic study of metabolic enzymes and transporters. Pharmacogenomics J 2017; 17(4): 325-30.
[http://dx.doi.org/10.1038/tpj.2016.31] [PMID: 27089937]
[47]
Lemos C, Giovannetti E, Zucali PA, et al. Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmacogenomics 2011; 12(2): 159-70.
[http://dx.doi.org/10.2217/pgs.10.172] [PMID: 21332310]
[48]
Guan S, Chen X, Xin S, et al. Establishment and application of a predictive model for gefitinib-induced severe rash based on pharmacometabolomic profiling and polymorphisms of transporters in non-small cell lung cancer. Transl Oncol 14(1): 100951.
[49]
Fukudo M, Ikemi Y, Togashi Y, et al. Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer. Clin Pharmacokinet 2013; 52(7): 593-609.
[http://dx.doi.org/10.1007/s40262-013-0058-5] [PMID: 23532985]
[50]
Noguchi Y, Tachi T, Teramachi H. Subset analysis for screening drug-drug interaction signal using pharmacovigilance database. Pharmaceutics 2020; 12(8): 762.
[http://dx.doi.org/10.3390/pharmaceutics12080762] [PMID: 32806518]
[51]
Monteith S, Glenn T. A comparison of potential psychiatric drug interactions from six drug interaction database programs. Psychiatry Res 2019; 275: 366-72.
[http://dx.doi.org/10.1016/j.psychres.2019.03.041] [PMID: 31003063]
[52]
Scheife RT, Hines LE, Boyce RD, et al. Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clini-cal decision support. Drug Saf 2015; 38(2): 197-206.
[http://dx.doi.org/10.1007/s40264-014-0262-8] [PMID: 25556085]
[53]
Vonbach P, Dubied A, Krähenbühl S, Beer JH. Evaluation of frequently used drug interaction screening programs. Pharm World Sci 2008; 30(4): 367-74.
[http://dx.doi.org/10.1007/s11096-008-9191-x] [PMID: 18415695]
[54]
Reis AMM, Cassiani SHDB. Evaluation of three brands of drug interaction software for use in intensive care units. Pharm World Sci 2010; 32(6): 822-8.
[http://dx.doi.org/10.1007/s11096-010-9445-2] [PMID: 20963634]
[55]
Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP. Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies. J Manag Care Pharm 2006; 12(5): 383-9.
[http://dx.doi.org/10.18553/jmcp.2006.12.5.383] [PMID: 16792445]
[56]
Muhič N, Mrhar A, Brvar M. Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: A prospective cohort study. Eur J Clin Pharmacol 2017; 73(7): 875-82.
[http://dx.doi.org/10.1007/s00228-017-2232-4] [PMID: 28299402]
[57]
Wang LM, Wong M, Lightwood JM, Cheng CM. Black box warning contraindicated comedications: Concordance among three major drug interaction screening programs. Ann Pharmacother 2010; 44(1): 28-34.
[http://dx.doi.org/10.1345/aph.1M475] [PMID: 20040698]
[58]
Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in cardiac and cardiothoracic intensive care units: An analysis of patients in an academic medical centre in the US. Drug Saf 2010; 33(10): 879-88.
[http://dx.doi.org/10.2165/11532340-000000000-00000] [PMID: 20812772]
[59]
Roblek T, Deticek A, Leskovar B, et al. Clinical-pharmacist intervention reduces clinically relevant drug-drug interactions in patients with heart failure: A randomized, double-blind, controlled trial. Int J Cardiol 2016; 203: 647-52.
[http://dx.doi.org/10.1016/j.ijcard.2015.10.206] [PMID: 26580349]
[60]
Slight SP, Seger DL, Nanji KC, et al. Are we heeding the warning signs? Examining providers’ overrides of computerized drug-drug interaction alerts in primary care. PLoS One 2013; 8(12): e85071.
[http://dx.doi.org/10.1371/journal.pone.0085071] [PMID: 24386447]
[61]
Yeh M-L, Chang Y-J, Wang P-Y, Li Y-CJ, Hsu C-Y. Physicians’ responses to computerized drug-drug interaction alerts for outpatients. Comput Methods Programs Biomed 2013; 111(1): 17-25.
[http://dx.doi.org/10.1016/j.cmpb.2013.02.006] [PMID: 23608682]
[62]
Ahn EK, Cho S-Y, Shin D, Jang C, Park RW. Differences of reasons for alert overrides on contraindicated co-prescriptions by admitting department. Healthc Inform Res 2014; 20(4): 280-7.
[http://dx.doi.org/10.4258/hir.2014.20.4.280] [PMID: 25405064]
[63]
Meslin SMM, Zheng WY, Day RO, Tay EMY, Baysari MT. Evaluation of clinical relevance of drug–drug interaction alerts prior to implementation. Appl Clin Inform 2018; 9(4): 849-55.
[http://dx.doi.org/10.1055/s-0038-1676039] [PMID: 30485879]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy