Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients

Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients. Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis. Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment. Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.