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 (R) 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.