Drug interactions profile of Oral Antineoplastic Agents (OAAs) dispensed for oncologic patients

Authors

DOI:

https://doi.org/10.33448/rsd-v9i8.5369

Keywords:

Neoplasms; Antineoplastic agents; Administration; oral; Drug interactions.

Abstract

The present study aims to list the oral antineoplastic agents (OAAs) most dispensed in an oncology hospital, identifying their doses, indications, contraindications and possible drug interactions (DIs). Documentary, retrospective, analytical and descriptive study, where OAAs dispensation spreadsheets were analyzed, from january to july 2019. Data were obtained from Micromedex® and analyzed by SPSS® (version 20) using descriptive statistics. 22 types of OAAs were dispensed, making a total of 360.703 drugs. Anastrozole was the most prescribed (51,85%) and hormone therapy agents (32%) were considered the main group. Tyrosine kinase inhibitors exposed the highest rates of contraindications (n=64). With regard to serious risk interactions, nilotinib (n=264), dasatinib (n=182) and metotrexate (n=134) were the drugs with the highest number of reports. The OAAs that did not present any type of interaction were anastrozole and diethylstilbestrol. Of the pharmacological agents that most interacted with OAAs, live vaccines (n=11) were the most present in contraindications and warfarin was the one that had the highest rate of serious interactions (n=8). As for the repercussions of DIs, the most frequent indices were the increased risk of prolongation of the QT interval (n=67) and increased exposure to a drug (n=51). Bearing in mind that cancer therapy requires special attention because of the possible interactions with OAAs, these results are shown to be a useful tool for the entire multiprofessional health team, especially the pharmacist, who has an essential role in the pharmaceutical assistance service on an outpatient basis.

Author Biographies

Herlem Silva Rodrigues, Centro Universitário Santo Agostinho

Graduando em Farmácia pelo Centro Universitário Santo Agostinho (UNIFSA). Tem experiência na área de Farmácia Hospitalar, Assistência e Atenção farmacêutica, com ênfase em Manipulação de Quimioterápicos.

Railson Pereira Souza, Universidade Federal do Piauí

Mestrando em Farmacologia de Produtos Naturais da Universidade Federal do Piauí (UFPI) / Núcleo de Pesquisa em Plantas Medicinais (NPPM), Laboratório de Farmacologia Cardiovascular (LAFAC). Farmacêutico graduado pela UFPI. Nutricionista graduado pelo Centro Unificado de Teresina (CEUT). Especialista em Ciências Forenses - Perícia Criminal pelo Instituto Educacional Santa Catarina (IESC) e em Farmacologia pela Faculdade Futura – Instituto de Ciência, Educação e Tecnologia de Votuporanga. Tem experiência na área de Farmácia & Nutrição, com ênfase em Farmacologia antitumoral e cardiovascular de produtos naturais, Farmacoterapia, Desenvolvimento de alimentos e cosméticos, Rotulagem Nutricional e Revisão/escrita de livros e artigos científicos.

Rayran Walter Ramos de Sousa, Universidade Federal do Piauí

Mestrando em Ciências Farmacêuticas pelo Programa de Pós-graduação em Ciências Farmacêuticas na Universidade Federal do Piauí (PPGCF/UFPI), linha de pesquisa Farmacologia e Toxicologia de Produtos Naturais e Sintéticos. Farmacêutico graduado pela UFPI, com experiência em Farmácia Comunitária, Tecnologia Farmacêutica e Cancerologia Experimental.

Layane Carneiro Alves Pereira, Universidade Federal do Piauí

Mestranda em Farmacologia de Produtos Naturais da Universidade Federal do Piauí (UFPI) / Núcleo de Pesquisa em Plantas Medicinais (NPPM). Graduada em Farmácia pela UFPI. Especialista em Farmácia Clínica e Farmacologia Clínica com ênfase em Prescrição Farmacêutica pelo Instituto Brasil de Pós-Graduação, Capacitação e Assessoria (IBRAS) - Faculdade Cathedral. Tem experiência nas áreas de Farmacologia, Fisiologia, Embriologia, Atenção Farmacêutica, Farmacologia Clínica e Pesquisa.

Renata Rodrigues de Oliveira Castelo Branco, Universidade Federal do Piauí

Mestranda em Farmacologia de Produtos Naturais da Universidade Federal do Piauí (UFPI) / Núcleo de Pesquisa em Plantas Medicinais (NPPM). Graduada em Farmácia pela UFPI. Especialista em Farmácia Clínica e Farmacologia Clínica com ênfase em Prescrição Farmacêutica pelo Instituto Brasil de Pós-Graduação, Capacitação e Assessoria (IBRAS) - Faculdade Cathedral. Possui experiência em Farmacologia dos Antimicrobianos e em Farmácia comunitária, prestando serviços de atenção farmacêutica e atendimento ao público.

Pedro Henrique Fernandes Paiva Silveira, Centro Universitário Santo Agostinho

Graduando em Farmácia pelo Centro Universitário Santo Agostinho (UNIFSA).

Maria Helena Rodrigues Mesquita Britto, Centro Universitário Santo Agostinho

Doutora em Farmacologia pela Faculdade de Ciências Médicas da Universidade Estadual de Campinas - UNICAMP.  Mestra em Bioengenharia pela Universidade Vale do Paraíba - UNIVAP. Graduada em Farmácia, com habilitação em Análises Clínicas pela Universidade Federal do Piauí. Docente no Centro Universitário Santo Agostinho (UNIFSA) nos cursos de Farmácia, Odontologia e Estética e cosmética. Atua na área de controle de qualidade de medicamentos, toxicologia e docagem molecular. 

References

Abdelgalil, A. A., Alam, M. A., Raish, M., Mohammed, I. E., Hassan Mohammed, A. E., Ansari, M. A., & Al Jenoobi, F. I. (2019). Dasatinib significantly reduced in vivo exposure to cyclosporine in a rat model: The possible involvement of CYP3A induction. Pharmacological reports, 71(2), 201–205. DOI: https://doi.org/10.1016/j.pharep.2018.10.018.

Akbulut, M., & Urun, Y. (2020). Onco-cardiology: Drug-drug interactions of antineoplastic and cardiovascular drugs. Critical reviews in oncology/hematology, 145, 102822. 1-7. DOI: https://doi.org/10.1016/j.critrevonc.2019.102822

Ariza-Heredia, E. J., & Chemaly, R. F. (2015). Practical review of immunizations in adult patients with cancer. Human vaccines & immunotherapeutics, 11(11), 2606–2614. DOI: https://doi.org/10.1080/21645515.2015.1062189

Atiq, F., Broers, A. E., Andrews, L. M., Doorduijn, J. K., Koch, B. C., Van Gelder, T., & Versmissen, J. (2016). A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib. European journal of clinical pharmacology, 72(6), 719–723. DOI: https://doi.org/10.1007/s00228-016-2038-9

Barros-Oliveira, M., Costa-Silva, D. R., Andrade, D. B., Borges, U. S., Tavares, C. B., Borges, R. S., Silva, J. M., & Silva, B. (2017). Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review. Revista da Associação Medica Brasileira (1992), 63(4), 371–378. DOI: https://doi.org/10.1590/1806-9282.63.04.371

Brasil. (2019). ABC do câncer: abordagens básicas para o controle do câncer. Instituto Nacional de Câncer José Alencar Gomes da Silva. 5. ed. URL: https://www.inca.gov.br/sites/ufu.sti.inca.local/files//media/document//livro-abc-5-edicao.pdf

Brasil. (2019). Estimativa 2020: incidência de câncer no Brasil. Instituto Nacional de Câncer José Alencar Gomes da Silva. – Rio de Janeiro. URL: https://www.inca.gov.br/sites/ufu.sti.inca.local/files/media/document/estimativa-2020-incidencia-de-cancer-no-brasil.pdf

Brasil, (2019). A situação do câncer de mama no Brasil: síntese de dados dos sistemas de informação. Instituto Nacional de Câncer José Alencar Gomes da Silva. – Rio de Janeiro. URL: https://www.inca.gov.br/sites/ufu.sti.inca.local/files/media/document/a_situacao_ca_ mama_brasil_2019.pdf

Brunsó, M. L., Blanch, C. T., Girona, E. S., García, D. R., Martínez, A. H., Font, A. I., Prió, S. G., Pueyo, H. G. M., & Bosch-Barrera, J. (2018). Probable drug-drug interaction between erlotinib and amiodarone causes severe neurotoxicity in a patient with advanced lung cancer. Anti-cancer drugs, 29(4), 380–383. DOI: https://doi.org/10.1097/CAD. 0000000000000600

Brunton, L. L.; Chabner, B. A.; Knollmann, B. C. (2012). As bases farmacológicas de Goodman & Gilman. 12. ed. Porto Alegre: Artmed.

Camidge, R., Reigner, B., Cassidy, J., Grange, S., Abt, M., Weidekamm, E., & Jodrell, D. (2005). Significant effect of capecitabine on the pharmacokinetics and pharmacodynamics of warfarin in patients with cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 23(21), 4719–4725. DOI: https://doi.org/ 10.1200/JCO.2005.09.129

Campos, G. R., Boin, I., Campos, I. D., Junior, & Cintra, M. L. (2017). Study of factors affecting the incidence of skin cancer in patients after liver transplant. Anais brasileiros de dermatologia, 92(4), 492–498. DOI: https://doi.org/10.1590/abd1806-4841.20175946.

Del Re, M., Fogli, S., Derosa, L., Massari, F., Souza, P., Crucitta, S., Bracarda, S., Santini, D., & Danesi, R. (2017). The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate/prednisone and enzalutamide. Cancer treatment reviews, 55, 71–82. DOI: https://doi.org/10.1016/j.ctrv.2017.03.001

Dudenkov, T. M., Liu, D., Cairns, J., Devarajan, S., Zhuang, Y., Ingle, J. N., Buzdar, A. U., Robson, M. E., Kubo, M., Batzler, A., Barman, P., Jenkins, G. D., Carlson, E. E., Goetz, M. P., Northfelt, D. W., Moreno-Aspitia, A., Desta, Z., Reid, J. M., Kalari, K. R., Wang, L., … Weinshilboum, R. M. (2019). Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clinical pharmacology and therapeutics, 106(1), 219–227. https://doi.org/10.1002/cpt.1359.

Eljaaly, K., Alshehri, S., Bhattacharjee, S., Al-Tawfiq, J. A., & Patanwala, A. E. (2019). Contraindicated drug-drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 25(5), 620–622. DOI: https://doi.org/10.1016/j.cmi.2018.08.002.

Ferdinandi, D. M. & Ferreira, A. A. (2009). Agentes alquilantes: reações adversas e complicações hematológicas. AC&T Científica, 1(1), 1-12. URL: http://www.ciencianews.com.br/arquivos/ACET/IMAGENS/revista_virtual/hematologia/artdamiana2.pdf

Fogli, S., Del Re, M., Curigliano, G., van Schaik, R. H., Lancellotti, P., & Danesi, R. (2019). Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors. Cancer treatment reviews, 74, 21–28. DOI: https://doi.org/10.1016/j.ctrv.2019.01.006.

Giugliano, F. M., Falivene, S., Esposito, E., Di Franco, R., Muto, M., D'Aiuto, M., & Muto, P. (2017). External radiotherapy for breast cancer in the elderly. Aging clinical and experimental research, 29(Suppl 1), 149–157. DOI: https://doi.org/10.1007/s40520-016-0655-x

Grassi, L., Nanni, M. G., Rodin, G., Li, M., & Caruso, R. (2018). The use of antidepressants in oncology: a review and practical tips for oncologists. Annals of oncology: official journal of the European Society for Medical Oncology, 29(1), 101–111. DOI: https://doi.org/10.1093/annonc/mdx526

Hrudikova Vyskocilova, E., Grundmann, M., Duricova, J., & Kacirova, I. (2017). Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the relationship between effect and dose/concentration. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 161(2), 134–143. DOI: https://doi.org/ 10.5507/bp.2017.016

Indini, A., Petrelli, F., Tomasello, G., Rijavec, E., Facciorusso, A., Grossi, F., & Ghidini, M. (2020). Impact of use of gastric-acid suppressants and oral anti-cancer agents on survival outcomes: a systematic review and meta-analysis. Cancers, 12(4), 998. 1-14. DOI: https://doi.org/10.3390/cancers12040998.

Katabathina, V. S., Menias, C. O., Tammisetti, V. S., Lubner, M. G., Kielar, A., Shaaban, A., Mansour, J., Surabhi, V. R., & Hara, A. K. (2016). Malignancy after Solid Organ Transplantation: Comprehensive Imaging Review. Radiographics: a review publication of the Radiological Society of North America, Inc, 36(5), 1390–1407. DOI: https://doi.org/10.1148/rg.2016150175.

Khan, Y., Zaidi, S. O., Razak, B. S., Zaki, M., & Malik, B. H. (2020). Use of new oral anticoagulants / direct oral anticoagulants in malignant patients. Cureus, 12(2), e7007. 1-14. DOI: https://doi.org/10.7759/cureus.7007.

Lopes, B. A., Emerenciano, M., Gonçalves, B. A., Vieira, T. M., Rossini, A., & Pombo-de-Oliveira, M. S. (2015). Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia. PloS one, 10(5), e0127308. 1-14. DOI: https://doi.org/10.1371/journal.pone.0127308

Lucas, A. T., Madden, A. J., & Zamboni, W. C. (2015). Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents. Expert opinion on drug metabolism & toxicology, 11(9), 1419–1433. DOI: https://doi.org/10.1517/1 7425255.2015.1057496

Malikova, J., Brixius-Anderko, S., Udhane, S. S., Parween, S., Dick, B., Bernhardt, R., & Pandey, A. V. (2017). CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2. The Journal of steroid biochemistry and molecular biology, 174, 192–200. DOI: https://doi.org/10.1016/j.jsbmb.2017.09.007

Manikandan, P., & Nagini, S. (2018). Cytochrome P450 structure, function and clinical significance: a review. Current drug targets, 19(1), 38-54. DOI: https://doi.org/10.2174/1389450118666170125144557.

Marques, P. A. C. & Piein, A. M. G. (2008). Fatores que influenciam a adesão de pacientes com câncer à terapia antineoplásica oral. Acta Paulista de Enfermagem, 21(2), 323-9. URL: https://www.scielo.br/pdf/ape/v21n2/pt_a15v21n2.pdf

Masnoon, N., Shakib, S., Kalisch-Ellett, L., & Caughey, G. E. (2017). What is polypharmacy? A systematic review of definitions. BMC geriatrics, 17(1), 230. 1-10. DOI: https://doi.org/10.1186/s12877-017-0621-2

Mesquita, M. E. R., & da Silva, R. P. (2016). Autocuidado e quimioterapia oral domiciliar: avaliação das práticas educativas dos enfermeiros sob a perspectiva de pacientes. Revista Brasileira de Cancerologia, 62(3), 237-245. DOI: https://doi.org/10.32635/2176-9745.RBC.2016v62n3.165

Morin, L., Johnell, K., Laroche, M. L., Fastbom, J., & Wastesson, J. W. (2018). The epidemiology of polypharmacy in older adults: register-based prospective cohort study. Clinical epidemiology, 10, 289–298. DOI: https://doi.org/10.2147/CLEP.S153458.

Mosarla, R. C., Vaduganathan, M., Qamar, A., Moslehi, J., Piazza, G., & Giugliano, R. P. (2019). Anticoagulation strategies in patients with cancer: review topic of the week. Journal of the American College of Cardiology, 73(11), 1336–1349. DOI: https://doi.org/10.1016/j.jacc.2019.01.017.

Mulder, F. I., van Es, N., Kraaijpoel, N., Di Nisio, M., Carrier, M., Duggal, A., Gaddh, M., Garcia, D., Grosso, M. A., Kakkar, A. K., Mercuri, M. F., Middeldorp, S., Royle, G., Segers, A., Shivakumar, S., Verhamme, P., Wang, T., Weitz, J. I., Zhang, G., Büller, H. R., Raskob, G. (2020). Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study. Thrombosis research, 185, 13–19. DOI: https://doi.org/10.1016/j.thromres.2019.11.007

Oliveira, A. T. & Queiroz, A. P. A. (2012). Perfil de uso da terapia antineoplásica oral: a importância da orientação farmacêutica. Revista Brasileira de Farmácia Hospitalar e Serviços de Saúde, 3(4), 24-29. URL: http://www.v1.sbrafh.org.br/ public/artigos/2012030420BR.pdf

Organização Mundial da Saúde - OMS. (2018). Informativo – Câncer. Acesso em 20 de Abril em https://www.paho.org/bra/index.php?option=com_content&view=article&id=5588:folha-informativa-cancer&Itemid=1094

Ozverel, C. S., Karaboz, I., & Nalbantsoy, A. (2017). Novel treatment strategies in cancer immunotherapy. Acta Biologica Turcica, 30(2), 36-51. URL: http://www.actabiologicaturcica.com/index.php/abt/article/view/143/131

Paixão, C. S., Santos, M. O., Ternes, Y. M. F., & Santos, R. S. (2016). Polimorfismos genéticos da família citocromo p450 e o câncer. Saúde & Ciência em Ação, 2(2), 118-133. DOI: http://dx.doi.org/10.1590/0100-69912014005012.

Parsad, S., & Ratain, M. J. (2017). Drug-drug interactions with oral antineoplastic agents. JAMA oncology, 3(6), 736–738. DOI: https://doi.org/10.1001/jamaoncol.2016.3323

Perrone-Filardi, P., Avogaro, A., Bonora, E., Colivicchi, F., Fioretto, P., Maggioni, A. P., Sesti, G., & Ferrannini, E. (2017). Mechanisms linking empagliflozin to cardiovascular and renal protection. International Journal of Cardiology, 241, 450–456. DOI: https://doi.org/10.1016/j.ijcard.2017.03.089.

Pisconti, S., Scarpati, G. D. V., Facchini, G., Cavaliere, C., D’Aniello, C., Friscinni, A., Melissano, A. & Perri, F. (2018). The evolving landscape of immunotherapy against cancer. World Cancer Research Journal, 5(1), e1042. 1-12.

Ranchon, F., Vial, T., Rioufol, C., Hénin, E., Falandry, C., Freyer, G., Trillet-Lenoir, V., Le Tourneau, C. & You, B. (2015). Concomitant drugs with low risks of drug-drug interactions for use in oncology clinical trials. Critical reviews in oncology/hematology, 94(2), 189–200. DOI: https://doi.org/10.1016/j.critrevonc.2014.12.014.

Retamero, A. & Conde-Estévez, D. (2017). Erlotinib and acid suppressive agents: is it worth to take a coke?. Annals of oncology: official journal of the European Society for Medical Oncology, 28(1), 192–193. DOI: https://doi.org/10.1093/annonc/mdw530.

Rodallec, A., Fanciullino, R., Lacarelle, B. & Ciccolini, J. (2018). Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles. Expert review of clinical pharmacology, 11(6), 599–610. DOI: https://doi.org/10.1080/17512433.2018.1477586

Rogala, B. G., Charpentier, M. M., Nguyen, M. K., Landolf, K. M., Hamad, L. & Gaertner, K. M. (2019). Oral anticancer therapy: management of drug interactions. Journal of oncology practice, 15(2), 81–90. DOI: https://doi.org/10.1200/JOP.18.00483

Silva, A., Carlotto, J. & Rotta, I. (2018). Standardization of the infusion sequence of antineoplastic drugs used in the treatment of breast and colorectal cancers. Einstein (Sao Paulo, Brazil), 16(2), eRW4074. DOI: https://doi.org/10.1590/S1679-45082018RW4074.

Srinivas, N. R. (2016). Pharmacokinetic interaction of rifampicin with oral versus intravenous anticancer drugs: challenges, dilemmas and paradoxical effects due to multiple mechanisms. Drugs in R&D, 16(2), 141–148. DOI: https://doi.org/10.1007/s40268-016-0133-0.

Teo, Y. L., Ho, H. K., & Chan, A. (2015). Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. British journal of clinical pharmacology, 79(2), 241–253. DOI: https://doi.org/10.1111/bcp.12496.

Tohme, S., Simmons, R. L. & Tsung, A. (2017). Surgery for cancer: a trigger for metastases. Cancer research, 77(7), 1548–1552. DOI: https://doi.org/10.1158/0008-5472.CAN-16-1536

Tornio, A., & Backman, J. T. (2018). Cytochrome P450 in Pharmacogenetics: An Update. Advances in pharmacology (San Diego, Calif.), 83, 3–32. DOI: https://doi.org/10.1016/bs.apha.2018.04.007.

Wang, L., Zhan, Y., Wu, Z., Lin, M., Jin, X., Jiang, L., & Qiu, Y. (2020). A novel multitarget kinase inhibitor BZG with potent anticancer activity in vitro and vivo enhances efficacy of sorafenib through PI3K pathways in hepatocellular carcinoma cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 125, 110033. DOI: https://doi.org/10.1016/j.biopha.2020.110033.

Downloads

Published

28/06/2020

How to Cite

RODRIGUES, H. S.; SOUZA, R. P.; SOUSA, R. W. R. de; PEREIRA, L. C. A.; BRANCO, R. R. de O. C.; SILVEIRA, P. H. F. P.; BRITTO, M. H. R. M. Drug interactions profile of Oral Antineoplastic Agents (OAAs) dispensed for oncologic patients. Research, Society and Development, [S. l.], v. 9, n. 8, p. e145985369, 2020. DOI: 10.33448/rsd-v9i8.5369. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/5369. Acesso em: 23 nov. 2024.

Issue

Vol. 9 No. 8

Section

Health Sciences

License

Authors who publish with this journal agree to the following terms:

1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.