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

• Published in: Cancer chemotherapy and pharmacology Vol. 83; no. 5; pp. 827 - 835
• Main Authors: Sanchez, Lydia, Bacle, Astrid, Lamy, Thierry, Le Corre, Pascal
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2019; Springer Nature B.V; Springer Verlag
• Subjects: Bone marrow; Bone marrow transplantation; Cancer; Cancer Research; Chemotherapy; Density; Drug Interactions; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - etiology; Drugs; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Immunosuppressive agents; Intensive Care Units - statistics & numerical data; Kidney - drug effects; Length of Stay; Life Sciences; Medicine; Medicine & Public Health; Methotrexate; Middle Aged; Omeprazole; Oncology; Original Article; Patients; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - metabolism; Pharmaceutical sciences; Pharmacodynamics; Pharmacology; Pharmacology/Toxicology; Renal function; Retrospective Studies; Stem cell transplantation; Stem cells; Tramadol; Transplantation; Transplants & implants; Vincristine; Hematopoietic stem cell transplant; Pharmacodynamic; Bone marrow transplantation unit stay; Nephrotoxicity; Pharmacokinetic; Drug–drug interactions
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-019-03791-9

Purpose
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.
Methods
Retrospective study in 31 adult patients consecutively admitted to the BMTU.
Results
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.
Conclusions
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.