A Clinically Relevant Drug Interaction Between Busulfan and Rifampin in the Setting of Hematopoietic Stem Cell Transplant Conditioning

Busulfan is an alkylating agent used in combination with other chemotherapeutic agents and has become a common component of conditioning regimens prior to hematopoietic stem cell transplantation. Busulfan has a very narrow therapeutic index corresponding to the area under the plasma concentration-time curve, with supra-therapeutic busulfan levels associated with hepatic and neurologic toxicity and increased transplant-related mortality, while sub-therapeutic levels can be ineffective, resulting in disease relapse or graft failure. Busulfan is believed to be metabolized in the liver via conjugation with glutathione as well as cytochrome P450 isoenzymes. Interactions with medications known to affect CYP3A4, including phenytoin and metronidazole, have been described in multiple instances. This case discusses a drug-drug interaction between busulfan and rifampin, a known CYP3A4 inducer that has limited evidence currently in the literature. Busulfan therapeutic drug monitoring revealed accelerated busulfan clearance determined to be due to rifampin's effect on busulfan metabolism.