Potential drug–drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay
Studies have documented potential drug–drug interactions (pDDIs) 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 supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay.
Retrospective study in 31 adult patients consecutively admitted to the BMTU.
Prevalence of pharmacokinetic interactions was ten times lower than the pharmacodynamic interactions. The contraindications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDIs were ciclosporine, methotrexate, esomeprazole, tramadol, and vincristine. The median number of potential nephrotoxicity-related DDIs per patient was 7 and the median number of days during which nephrotoxicity-related DDIs 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.
Potential DDIs in HCST patients in BMTU were quite common. The DDIs 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.
KeywordsPharmacokinetic Pharmacodynamic Drug–drug interactions Hematopoietic stem cell transplant Bone marrow transplantation unit stay Nephrotoxicity
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by the Institutional Ethical committee of our institution with a waiver of patient consent authorization (No. 18.76). Since the design of the study is retrospective, no formal consent is required.
- 16.Gholaminezhad S, Hadjibabaie M, Gholami K, Javadi MR, Radfar M, Karimzadeh I, Ghavamzadeh A (2014) Pattern and associated factors of potential drug-drug interactions in both pre- and early post-hematopoietic stem cell transplantation stages at a referral center in the Middle East. Ann Hematol 93:1913–1922CrossRefGoogle Scholar
- 21.Hingorani S, Pao E, Stevenson P, Schoch G, Laskin BL, Gooley T, McDonald GB (2018) Changes in glomerular filtration rate and impact on long-term survival among adults after hematopoietic cell transplantation: a prospective cohort study. Clin J Am Soc NephrolGoogle Scholar
- 23.Clinical Practice Guidelines For Chronic Kidney Disease: Evaluation, Classification and Stratification. National Kidney Foundation, Kidney Disease Outcomes Quality Initiative (2002)Google Scholar
- 32.US Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#4. Accessed 30 may 2018