Avaliação de interações medicamentosas potenciais em pacientes oncopediátricos internados
DOI: 10.15343/0104-7809.202145034044
Palabras clave:
Antineoplásicos. Câncer. Farmacoterapia. Oncologia.Resumen
O câncer é uma doença caracterizada pelo crescimento desordenado de células com capacidade de invadir tecidos adjacentes. Na oncologia pediátrica, as interações ocorrem principalmente com medicamentos de suporte prescritos durante o tratamento. Com isso, o presente estudo realizou a revisão da farmacoterapia para identificar e avaliar as interações medicamentosas potenciais (IMP) em pacientes oncopediátricos internados em um hospital público. Analisou-se 203 prescrições de 47 pacientes. Foi identificado 55 IMP no total, sendo 14 IMP diferentes e 1,2 IMP por paciente. A mais prevalente em 47,2% do total (n = 26) foi entre metotrexato e cotrimoxazol. Identificou-se 21 tipos de neoplasias, sendo a mais frequente a leucemia linfoblástica aguda (LLA). A correlação de Spearman foi + 0,71 (p < 0,001), indicando uma forte correlação entre a ocorrência de interações medicamentosas com número de medicamentos prescritos. Na análise de regressão logística multivariada os resultados demonstraram que apresentar LLA e polifarmácia foram os principais fatores associados para ocorrência de IMP. Destaca-se a probabilidade de ocorrência de IMP aumentar 9,7 vezes em pacientes polimedicados IC95% = 4,6-21,4 (p = 0,001) e OR em 12,1; IC95% = 5,8-26,9 em pacientes com LLA comparando os que não apresentam LLA (p = 0,001). Nessa perspectiva, os dados obtidos possibilitam fornecer subsídios para a implementação de estratégias de monitoramento das IMP, bem como de intervenções clínicas que garantam uma terapêutica mais eficaz contribuindo para a segurança dos pacientes oncopediátricos.
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25. Byrnes DM, Vargas F, Dermarkarian C, Kahn R, Kwon D, Hurley J, Schatz JH. Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients. J Oncol. 2019 Mai;2019: 4047617, doi: 10.1155/2019/4047617.
26. Kwong YL,Yeung DYM, Chan JCW. Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities. Ann Hematol. 2009 Mar;88(3):193–201, doi: 10.1007/s00277-008-0645-y.
27. Cudmore J, Seftel M, Sisler J, Zarychanski R. Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur. Can Fam Physicians. 2014 Jan;60(1):53–6.
28. Balk TE, van der Sijs IH, van Gelder T, Janssen JJB, van der Sluis IM, van Leeuwen RWF, and Engels FK. Drug-drug interactions in pediatric oncology patients. Pediatr Blood Cancer. 2017 Jul;64(7), doi: 10.1002/pbc.26410.
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30. Chabner B, Roberts Jr TG. Chemotherapy and the war on cancer. Nat Rev Cancer. 2005 Jan;5(1):65–72, doi: 10.1038/nrc1529.
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32. Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei, D, et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol. 2009 Dez;27(35):5972–78, doi: 10.1200/JCO.2008.20.4156.
33. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J Piñan MA, Garcia-Miguel P, Navajas A, et al. Polymorphisms of the SLCO1B1 gene predict methotrexate related toxicity in childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2011 Out;57(4):612–19, doi: 10.1002/pbc.23074.
34. Crom WR. Methotrexate. In: A Clinician’s Guide to Chemotherapy Pharmacokinetics and Pharmacodynamics. J Natl Cancer Inst 1999 Fev;91(3):283-4, doi: 10.1093/jnci/91.3.283.
35. Buchen S, Ngampolo D, Melton RG, Hasan C, Zoubek A, Henze G, et al. Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer. 2005;92(3):480–87, doi: 10.1038/sj.bjc.6602337.
36. Rees CA, Lennard L, Lilleyman JS, Maddocks JL. Disturbance of 6-mercaptopurine metabolism by cotrimoxazole in childhood lymphoblastic leukaemia. Cancer Chemoth Pharm. 1984;12(2):87-9, doi: 10.1007/BF00254595.
37. Duarte NC, Barbosa CR, Tavares MG, Dias LP, Souza RN, Moriel P. Clinical oncology pharmacist: Effective contribution to patient. J Oncol Pharm Pract. 2019 Out;25(7):1665-1674, doi: 10.1177/1078155218807748.
38. Farrag DK, Sabri NA, Tawfik AS, Shaheen, SM. Evaluation of the clinical effect of pharmacist intervention. E J Oncol Pharm. 2020 Jan-Mar;3(1):e23, doi: 10.1097/OP9.0000000000000023.
2. Atun R, Bhakta N, Denburg A, Frazier AL, Friedrich P, Gupta S, et al. Sustainable care for children with cancer: a Lancet Oncology Commission. Lancet Oncol. 2017 Abr;21 (4):e185–e224, doi: 10.1016/S1470-2045(20)30022-X.
3. Brasil. Ministério da Saúde. Instituto Nacional do Câncer José Alencar Gomes da Silva. Câncer infanto juvenil. Inca, 2020 [acessado 2020 Set 14]. Disponível em: https://www.inca.gov.br/tipos-de-cancer/cancer-infantojuvenil.
4. Wang JK, Herzog NS. Kaushal R, Park C, Mochizuki C, Weingarten SR. Prevention of pediatric medication errors by hospital pharmacists and the potential benefit of computerized physician order entry. Pediatrics. 2007 Jan;119(1):77-85, doi: 10.1542/peds.2006-0034.
5. Morales-Ríos O, Jasso-Gutiérrez L, Reyes-López A, Garduño-Espinosa J, Muñoz-Hernández, O. Potential drug-drug interactions and their risk factors in pediatric patients admitted to the emergency department of a tertiary care hospital in Mexico. Plos One. 2018 Jan;13(1):1-14, doi: 10.1371/journal.pone.0190882.
6. Fernández de Palencia Espinosa MA, Díaz Carrasco MS, Fuster Soler JL, Ruíz Merino G, De la Rubia Nieto MA, Espuny Miró A. Pharmacoepidemiological study of drug-drug interactions in onco-hematological pediatric patients. Int J Clin Pharm. 2014 Dez;36:1160–1169, doi: 10.1007/s11096-014-0011-1.
7. Secoli SR. Interações medicamentosas: fundamentos para a prática clínica da enfermagem. Rev Esc Enferm. 2001 Mar;35(1):28-34, doi: https://doi.org/10.1590/S0080-62342001000100005.
8. Sharma S, Chhetriand HP, Alam K. A study of potential drug-drug interactions among hospitalized cardiac patients in a teaching hospital in Western Nepal. Indian J Pharmacol. 2014 Mar-Abr;46(2):152-156, doi: 10.4103/0253-7613.129303.
9. World Health Organization (WHO). Patient safety: making health care safer. [Internet]. 2017 [Acessado 2018 Dez 15]. Disponível em: https://apps.who.int/iris/handle/10665/255507.
10. Haidar, C, Jeha, S. Drug interactions in childhood cancer. Lancet Oncol. 2011 Jan; 12(1):92–99, doi: 10.1016/S1470-2045(10)70105-4.
11. World Health Organization (WHO), Collaborating Centre for Drug Statistics Methodology. Anatomical Therapeutic Chemical Index ATC/DDD, 2016. Geneva: WHO; 2016 [acessado 2019 Out 10]. Disponível em: http://www.whocc.no/atc_ddd_index/.
12. Micromedex® Healthcare Series: MICROMEDEX. Versão 2.0 [plataforma na internet].
13. Organização Mundial da Saúde (OMS). CID-10 - Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde. 10ª revisão. Brasília: Centro Colaborador da OMS para Classificação de Doenças em Português; 1995.
14. R Development Core Team (2019). R: a Language and Environment for Statistical Computing [Internet]. Vienna: R Foundation for Statistical Computing; 2013. Disponível em: https://www.R-project.org.
15. Plenário do Conselho Nacional de Saúde (Brasil). Resolução nº 466/2012, publicada no Diário Oficial da União (DOU) em 13 de julho de 2013 [acessado 2020 Ago 25]. Disponível em: https://conselho.saude.gov.br/resolucoes/2012/Reso466.pdf.
16. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991 Jun;148(6):705–13, doi: 10.1176/ajp.148.6.705.
17. Boyer EW, Shannon M. The Serotonin syndrome. N Engl J Med. 2005 Mar;352(11):1112-20, doi: 10.1056/NEJMra041867.
18. Hymel N, Davies M. Evidence-Based Antiemetic Decision Tool for Management of Postoperative Nausea and Vomiting in Patients at High Risk of QT Prolongation and Patients Receiving Neurotransmitter-Modulating Medications. AANA J. 2020 Ago;88(4):312-318. PMID: 32718430.
19. Robak T. Clinical pharmacology of ondansetron. Acta Haematol Pol. 1993;24(2):103-13.
20. Cagnoni PJ, Matthes S, Day TC, Bearman SI, Shpall EJ, Jones RB. Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. Bone Marrow Transplant 1999 Jul;24(1):1−4, doi: 10.1038/sj.bmt.1701832.
21. Löwenberg B, Downing JR, Burnet A. Acute myeloid leukemia. N England J Med. 1999 Set;341:1051–62, doi: 10.1056/NEJM199909303411407.
22. Herzig RH, Hines JD, Herzig GP, Wolff SN, Cassileth PA, Lazarus HM, et al. Cerebellar toxicity with high-dose cytosine arabinoside. J Clin Oncol. 1987 Jun;5(6):927–932, doi: 10.1200/JCO.1987.5.6.927.
23. Momparler, RL. Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia. Exp Hematol Oncol. 2013 Ago;2(1):1-5, doi: 10.1186/2162-3619-2-20.
24. Brandalise SR. Comparison of intermittent versus continuous methotrexate plus 6-mp in maintenance regimen for standard risk acute lymphoblastic leukemia in children (GBTLI ALL-99). J Clin Oncol. 2007 Jun;25(Suppl.18): 9512-9512, doi: 10.1200/jco.2007.25.18_suppl.9512.
25. Byrnes DM, Vargas F, Dermarkarian C, Kahn R, Kwon D, Hurley J, Schatz JH. Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients. J Oncol. 2019 Mai;2019: 4047617, doi: 10.1155/2019/4047617.
26. Kwong YL,Yeung DYM, Chan JCW. Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities. Ann Hematol. 2009 Mar;88(3):193–201, doi: 10.1007/s00277-008-0645-y.
27. Cudmore J, Seftel M, Sisler J, Zarychanski R. Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur. Can Fam Physicians. 2014 Jan;60(1):53–6.
28. Balk TE, van der Sijs IH, van Gelder T, Janssen JJB, van der Sluis IM, van Leeuwen RWF, and Engels FK. Drug-drug interactions in pediatric oncology patients. Pediatr Blood Cancer. 2017 Jul;64(7), doi: 10.1002/pbc.26410.
29. Watts CS, Sciasci JN, Pauley JL, Panetta JC, Pei D, Cheng C, Christensen CM, Mikkelsen TS, Pui CH, Jeha S, Relling MV. Prophylactic trimethoprim sulfamethoxazole does not affect pharmacokinetics or pharmacodynamics of methotrexate. Pediatr Hematol Oncol J. 2016 Ago;38(6):449- 52, doi: 10.1097/MPH.0000000000000606.
30. Chabner B, Roberts Jr TG. Chemotherapy and the war on cancer. Nat Rev Cancer. 2005 Jan;5(1):65–72, doi: 10.1038/nrc1529.
31. Levêque D , Santucci R, Gourieux B, Herbrecht R. Pharmacokinetic drug-drug interactions with methotrexate in oncology. Expert Rev Clin Pharmacol. 2011 Nov;4(6):743-50, doi: 10.1586/ecp.11.57.
32. Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei, D, et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol. 2009 Dez;27(35):5972–78, doi: 10.1200/JCO.2008.20.4156.
33. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J Piñan MA, Garcia-Miguel P, Navajas A, et al. Polymorphisms of the SLCO1B1 gene predict methotrexate related toxicity in childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2011 Out;57(4):612–19, doi: 10.1002/pbc.23074.
34. Crom WR. Methotrexate. In: A Clinician’s Guide to Chemotherapy Pharmacokinetics and Pharmacodynamics. J Natl Cancer Inst 1999 Fev;91(3):283-4, doi: 10.1093/jnci/91.3.283.
35. Buchen S, Ngampolo D, Melton RG, Hasan C, Zoubek A, Henze G, et al. Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer. 2005;92(3):480–87, doi: 10.1038/sj.bjc.6602337.
36. Rees CA, Lennard L, Lilleyman JS, Maddocks JL. Disturbance of 6-mercaptopurine metabolism by cotrimoxazole in childhood lymphoblastic leukaemia. Cancer Chemoth Pharm. 1984;12(2):87-9, doi: 10.1007/BF00254595.
37. Duarte NC, Barbosa CR, Tavares MG, Dias LP, Souza RN, Moriel P. Clinical oncology pharmacist: Effective contribution to patient. J Oncol Pharm Pract. 2019 Out;25(7):1665-1674, doi: 10.1177/1078155218807748.
38. Farrag DK, Sabri NA, Tawfik AS, Shaheen, SM. Evaluation of the clinical effect of pharmacist intervention. E J Oncol Pharm. 2020 Jan-Mar;3(1):e23, doi: 10.1097/OP9.0000000000000023.
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2021-02-23
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de Souza Ribeiro, E. ., & Christianne Batista de Lacerda Pedrosa, S. (2021). Avaliação de interações medicamentosas potenciais em pacientes oncopediátricos internados: DOI: 10.15343/0104-7809.202145034044. O Mundo Da Saúde, 45, 034–044. Recuperado a partir de https://revistamundodasaude.emnuvens.com.br/mundodasaude/article/view/1012
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