Amiodarone-sirolimus/tacrolimus interaction in a pediatric heart transplant patient

A two year-old female who had underwent ABO-incompatible heart transplantation at four months of age was admitted with unexplained anemia and renal dysfunction. The patient also had evidence of moderate liver dysfunction. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and prednisolone. Tacrolimus was held on day 2 for five days because of an elevated trough blood concentration. The patient required one fourth of her maintenance dose to keep trough concentrations within the target range. Nadolol and amiodarone were prescribed on day 7 to control ventricular arrhythmias. Sirolimus was prescribed on day 11. A precautionary (non-steady-state) sirolimus trough concentration was grossly elevated. Sirolimus was held and tacrolimus was discontinued. Sirolimus blood concentrations remained above the target range for fourteen days despite successive dose manipulations. The patient succumbed from complications of ECMO on day 42. Amiodarone and cyclosporine interactions in the solid organ transplant population have been previously described. To our knowledge, there are no cases of amiodarone and sirolimus or tacrolimus interactions reported in English literature. Both tacrolimus and sirolimus are metabolized through the same enzyme system as cyclosporine, and the chance of a similar interaction occurring is high. Sirolimus is also a substrate of p-glycoprotein and thus may be significantly affected by amiodarone. We have described a potential interaction with sirolimus, tacrolimus and amiodarone. If amiodarone is deemed the most appropriate choice for the patient, clinicians should consider prospectively decreasing sirolimus and tacrolimus doses. Blood concentrations should also be monitored more frequently in order to minimize prolonged periods of supratherapeutic concentrations and related toxicities.