Evaluation of potential drug interactions in hospitalized pediatric oncology patients
DOI: 10.15343/0104-7809.202145034044
Keywords:
Antineoplastics. Cancer. Pharmacotherapy. Oncology.Abstract
Cancer is a disease characterized by the disordered growth of cells capable of invading adjacent tissues. In pediatric oncology, drug-drug interactions occur mainly with supportive drugs prescribed during treatment. Thus, the present study aims to identify and evaluate the potential drug-drug interactions (PDDIs) in hospitalized pediatric oncology patients. 203 prescriptions of 47 patients were analyzed. A total of 55 PDDIs were identified, with 14 different PDDIs, and 1.2 PDDI per patient. The most prevalent 47.2% (n = 26) was methotrexate and cotrimoxazole. 21 types of neoplasms were identified, the most frequent being acute lymphoblastic leukemia (ALL). The Spearman correlation was +0.71 (p<0.001), indicating a strong correlation with the occurrence of potential drug-drug interactions and the number of drugs prescribed. In the multivariate logistic regression analysis, the results showed that having ALL and polypharmacy were the main associated factors for the occurrence of PDDI. The probability of the occurrence of PDDIs increases by 9.7 times in polymedicated patients (95%CI = 4.6-21.4 (p=0.001)) and 12.1 times in ALL patients compared to those without ALL (95% CI=5.8-26.9 (p = 0.001)). In this perspective, the data obtained make it possible to provide subsidies for the implementation of strategies to monitor and provide clinical interventions that guarantee a more effective treatment, contributing to the safety of pediatric oncology patients.
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References
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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.
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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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Published
2021-02-23
How to Cite
de Souza Ribeiro, E. ., & Christianne Batista de Lacerda Pedrosa, S. (2021). Evaluation of potential drug interactions in hospitalized pediatric oncology patients: DOI: 10.15343/0104-7809.202145034044. O Mundo Da Saúde, 45, 034–044. Retrieved from https://revistamundodasaude.emnuvens.com.br/mundodasaude/article/view/1012
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