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

Lydia Sanchez (1) , Astrid Bacle (2, 3, 4) , Thierry Lamy (5, 1) , Pascal Le Corre (2, 3, 4)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 Irset - Institut de recherche en santé, environnement et travail
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 UR Pharmacie - Université de Rennes - Faculté des sciences pharmaceutiques et biologiques
5 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer

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.

Mots clés: Pharmacokinetic; Pharmacodynamic; Hematopoietic stem cell transplant; Drug–drug interactions; Bone marrow transplantation unit stay; Nephrotoxicity

Domaines: Cancer; Pharmacologie

Lydia Sanchez, Astrid Bacle, Thierry Lamy, Pascal Le Corre. Potential drug-drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay. Cancer Chemotherapy and Pharmacology, 2019, 83 (5), pp.827-835. ⟨10.1007/s00280-019-03791-9⟩. ⟨hal-02061952⟩