Association between potential drug interactions and clinical outcomes in hematopoietic stem cell transplantations

Abstract

The association of anti-infective, antineoplastic and immunosuppressant drugs makes patients undergoing hematopoietic stem cell transplantation susceptible to the effects resulting from drug interactions. In this study, we analyzed the potential drug interactions in the association between anti-infective, antineoplastic and immunomodulators agents and their clinical effects presented by patients from a bone marrow transplant service of a Brazilian hospital specialized in cancer treatment. The retrospective cohort involved patients in the conditioning phase undergoing transplantation in the year 2013. The chi-square test was used to assess the association and the confidence interval considered was 95%. A total of 53 patients were included in the study and 69.8% ( p = 0.004) presented some potential drug interaction. Of these, 97.3% ( p < 0.001) exhibited some symptom that may be associated with these interactions. Interactions with cyclophosphamide and cyclosporine were the most serious effects. There has been a high frequency and variety of interactions that may impair the entire transplant process, putting the patient's life at risk. The potential interactions observed during the conditioning period were associated with the symptoms presented by the patients. Strategies are needed to minimize negative outcomes in transplant patients.

Impact of the insertion of the clinical pharmacist in the Allogeneic Hematopoietic Stem Cells Transplantation team

“…Exposure to several and complex pharmacological schemes involving drugs with narrow therapeutic indexes and unfavorable safety profiles increases the potential for the occurrence of drug interactions and adverse reactions. 20 Some drugs with these characteristics and routinely applied at the HSCT are among the most frequently involved in DRPs in this study, voriconazole and cyclosporine standing out. Similarly, Valverde and collaborators show that the most frequent and intense symptoms reported in the medical records of patients with HSCT occur due to drug interactions involving cyclosporine, 20 a drug that undergoes extensive hepatic metabolism and is a substrate and inhibitor of CYP3A4 and of glycoprotein P. 19 In a Spanish study on drug interactions in hospitalized hematologic patients, the immunosuppressive agents and azole antifungals were the drugs most commonly involved.…”

“…The fundamental drugs for the success of HSCT are also the major causes for the morbidity associated with drugs during the treatment: anti-infectives, antineoplastics, and immunomodulators. 20 Similarly, these were the drug classes more involved in DRPs and team's doubts. The same data was found by Prot-Labarte and collaborators (29% anti-infectives, 28% antineoplastics and immunomodulators) 27 and by Wu and collaborators (13% anti-infectives, 30% antineoplastics and immunomodulators).…”

Impacto da inserção do farmacêutico clínico na equipe de transplante alogênico de células-tronco hematopoiéticas

“…Os regimes de condicionamento são variados e os principais medicamentos utilizados são: ciclofosfamida, bussulfano, fludarabina, melfalano, citarabina, etoposídeo e carmustina (SPYRIDONIDIS et al, 2020). Os protocolos são bem definidos e utilizados em diversos centros no mundo todo, contudo, é preciso considerar as particularidades do paciente e fazer ajustes necessários para otimizar o tratamento, sempre considerando os riscos e benefícios para o paciente (VALVERDE; DA SILVA; RETTO, 2019).…”

“…O risco de interações clinicamente significativas é amplificado pelas frequentes comorbidades e regulares complicações nesta população de pacientes, como os problemas renais e hepáticos, o estado nutricional deficiente e a alteração nas proteínas plasmáticas (CARRERAS et al, 2019). Como os pacientes de TCTH são mais suscetíveis à ocorrência de interações e aos seus efeitos, pesquisadores Universidade da Flórida sugerem que os medicamentos a serem incluídos nos protocolos e prescritos durante o TCTH devem ser analisados quanto ao seu potencial interativo com os outros medicamentos em uso (LEATHER, 2004;VALVERDE;RETTO, 2019).…”

“…A equipe de saúde deve estar atenta aos sintomas apresentados pelos pacientes, considerando sempre uma possível correlação com a ocorrência de interações medicamentosas e efeitos adversos. Também é importante conhecer o manejo a ser adotado para reduzir esses efeitos e evitar que o paciente seja prejudicado (VALVERDE; DA SILVA; RETTO, 2019). A literatura médica que descreve e orienta o manejo das interações medicamento-medicamento, medicamento-alimento e das interações farmacêuticas é muitas vezes difícil de interpretar, em virtude das grandes disparidades na definição das respostas às interações e da severa variação entre os indivíduos, justificada por fatores genéticos e particularidades clínicas.…”