Drug-drug interactions in patients undergoing hematopoietic stem cell transplantation: systematic review.

OBJECTIVE: The present paper provides a systematic review aimed at identifying studies on pharmacological interactions in patients  undergoing hematopoietic stem cell transplantation. Secondary objectives  include a characterization of the prevalence of such interactions and an  investigation of their specific characteristics.

METHOD: A search was performed of the terms "drug-drug interaction", "drug interaction", "stem cell transplant", "transplantation  conditioning", and "conditioning regimen" in the PubMed database, and of  the terms "drug interaction", "stem cell transplantation", and  "transplantation conditioning" in the Embase database. Only results  directly related to the objective of the review were selected. Studies in  humans published between January 2000 and November 2020, written in  English or Spanish, were prioritized.

RESULTS: The review identified two groups of studies: epidemiological studies and studies analyzing interactions between specific drugs. The 10 epidemiological studies selected, which showed a prevalence of interactions between 60 and 100%, mainly used the Micromedex®  database, focused on pharmacokinetic interactions involving azole  antifungals.Results were highly heterogeneous. Of the 52 drug interaction studies reviewed, the majority were pharmacokinetic and focused primarily on the interactions of azole antifungals with calcineurin inhibitors. Some  studies described the possible relationship between the interactions and  specific adverse reactions or deaths from adverse events.

CONCLUSIONS: The prevalence of drug-drug interactions in patients  undergoing hematopoietic stem cell transplantation is high, with  heterogeneous results both in terms of prevalence and of the profile of the interactions resulting from the use of disparate study designs and  databases. The most common factor associated with drug-drug  interactions was the number of drugs administered. Studies evaluating  drug-drug interactions are mostly pharmacokinetic and focus mainly on  azole antifungals and calcineurin inhibitors. It would be important to unify  the criteria followed in epidemiological studies to obtain results that may  help establish risk reduction strategies and conduct a more in-depth  investigation into the pharmacodynamic mechanisms involved and into the interactions between other drugs frequently used in patients undergoing  transplantation, including those recently introduced in our therapeutic  arsenal.