Prior Amiodarone Exposure Reduces Tacrolimus Dosing Requirements in Heart Transplant Recipients

Abstract

Introduction: Amiodarone use prior to heart transplant is independently associated with a higher rate of severe primary graft dysfunction and in-hospital mortality. Amiodarone may also alter the pharmacokinetics of medications metabolized via cytochrome P450. No data exist regarding the interaction between pretransplant amiodarone and tacrolimus concentrations. Design: Single-center retrospective study of transplant patients between January 1, 2014, and June 30, 2016. A therapeutic tacrolimus concentration was defined as a trough level between 8 and 15 ng/mL for 2 consecutive days. The primary outcome was the tacrolimus therapeutic weight-based dosing requirements (mg/kg/day) for patients receiving amiodarone prior to transplant when compared to those without prior receipt of amiodarone. Secondary outcomes include the incidence of cellular rejection and mortality within 6 months posttransplant. Results: Multi-organ transplant recipients (n ¼ 3), retransplants (n ¼ 9), those who died prior to a therapeutic level (n ¼ 1), and those receiving amiodarone posttransplant (n ¼ 7) were excluded from the analysis. Of the 80 patients included, 34 (42%) received amiodarone prior to transplant. Patient characteristics were similar, with the exception of primary graft dysfunction incidence (38% in amiodarone vs 8.5% in control, P ¼ .001). The median therapeutic dose was 0.1 (interquartile range [IQR]: 0.07-0.12) versus 0.13 (IQR: 0.09-0.17) in the amiodarone and control groups, respectively, (P < .01). No significant difference in mortality or rejection was noted. Conclusion: Patients receiving amiodarone prior to transplant require a lower weight-based dose of tacrolimus.

Combined amiodarone and digitalis therapy before heart transplantation is associated with increased post‐transplant mortality

“…Therefore, close drug trough level monitoring with dosage adjustment is essential to avoid overdosing or underdosing. In addition to amiodarone, several other factors may influence serum levels of cyclosporine A or tacrolimus including age, gender, weight, glomerular filtration rate, and concomitant medication 1,33–37 . In this study, we found no significant differences between patients with or without pre‐transplant amiodarone use in dosage or drug trough levels of cyclosporine A or tacrolimus within 30 days after HTX.…”

“…In addition to amiodarone, several other factors may influence serum levels of cyclosporine A or tacrolimus including age, gender, weight, glomerular filtration rate, and concomitant medication. 1,[33][34][35][36][37] In this study, we found no significant differences between patients with or without pre-transplant amiodarone use in dosage or drug trough levels of cyclosporine A or tacrolimus within 30 days after HTX. Moreover, we found no significant difference between both groups in terms of acute rejection as cause of death within 30 days after HTX (all P ≥ 0.05).…”

Role of the Transplant Pharmacist

“…AMD is metabolized through the CYP3A metabolic pathway, and it has been reported that patients receiving AMD prior to transplant require a reduction of the TAC dose [25]. It is therefore necessary to check blood levels of both AMD and TAC carefully.…”