Potential drug–drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay

Abstract

Purpose: Studies have documented potential drug-drug interactions (pDDI's) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents and supportivecare drugs, studies on potential DDI's are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDI's, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay. Method: retrospective study in 31 adult patients consecutively admitted to the BMTU. Results: Prevalence of pharmacokinetic interactions was 10-time lower than the pharmacodynamic interactions. The contra-indications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDI's were ciclosporine, methotrexate, esomeprazole, tramadol and vincristine. The median number of potential nephrotoxicity-related DDI's per patient was 7 and the median number of days during which nephrotoxicity-related DDI's potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions. Conclusions: Potential DDI's in HCST patients in BMTU were quite common. The DDI's from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.

Evaluation of the quality of life of adult patients admitted to the bone marrow transplantation unit

“…Similar indications have been reported in other studies done in adult BMT units. 11,13,16,17 In their study, Visani et al 18 found moderate oral mucositis in 26%, gastroenteritis in 35%, and moderate vomiting and nausea in all patients who underwent autologous stem cell transplantation. Nephrotoxicity, cardiotoxicity, and interstitial or idiopathic pneumonia were not detected in any of their patients.…”

A comparison of four drug–drug interaction databases for patients undergoing haematopoietic stem cell transplantation

“…Our study is consistent with the literature. Major drug groups causing DDIs were listed as immunosuppressants, antiepileptics and analgesics 9,39 . Gholaminezhad et al stated that antineoplastics such as busulfan and cyclophosphamide were common in drug–drug interactions in HSCT patients 40 …”

Therapeutic pathways of allogeneic and autologous hematopoietic stem cell transplantation recipients: a hospital pharmacist’s perspective

“…This is concerning because drugs metabolized by CYP3A4 are known to have potential interactions with other medications. Although the current study did not examine DDI, a previous study reported that DDIs in HSCT patients primarily resulted from pharmacokinetic mechanisms rather than pharmacodynamic interactions (1) .…”

“…Patients with hematological malignancies, especially those undergoing hematopoietic stem cell transplantation (HSCT), face a high risk of pharmacotherapy-related problems due to complex drug regimens and patho-physiological variations affecting clearance organs. Potential drug-drug interactions (DDIs) are particularly common among HSCT patients in the bone marrow transplantation unit (1) . The identification and resolution of drug-related problems (DRP) constitute a very important role of the clinical pharmacist in managing drug therapy, and several general guidelines and recommendations have been provided to define the role of hospital pharmacists in caring for HSCT patients (2)(3)(4)(5)(6) .…”