Is there an interaction between amiodarone and tacrolimus?/nA 56-year-old man with primary amyloido

Fråga: Is there an interaction between amiodarone and tacrolimus? A 56-year-old man with primary amyloidosis and heart-, kidney- and liver disease has recently recieved a liver transplant. He is being treated with tacrolimus, prednisolone, omeprazole, low molecular heparin and several antibiotics, as well as continuos hemodialysis (Prisma) and a temporary pacemaker. Due to atrial fibrillation and cardiac insufficiency, treatment with amiodarone is planned.

Sammanfattning: We have found no reports in the literature describing an interaction between tacrolimus and amiodarone. However, such an interaction is to be expected based on the known inhibitory effect of amiodarone on the CYP3A4 enzyme that metabolises tacrolimus. Both tacrolimus and amiodarone concentrations should be closely monitored during co-administration, and for several months after discontinuation of amiodarone.

Svar: Amiodarone is an antiarrhythmic drug with a very long half-life of about 60 days. It is metabolised in the liver, mainly by the cytochrome P450 (CYP) 3A4 enzyme, to an active metabolite, desethylamiodarone. Amiodarone and/or its main metabolite can inhibit the CYP3A4 enzyme and is known to interact with a number of drugs, including cyclosporine (1-4). Cyclosporine levels have been seen to increase more than two-fold after initiation of amiodarone treatment (3,4). Both tacrolimus and cyclosporine are extensively metabolised by CYP3A4, in the intestines and in the liver (5,6). Thus, amiodarone can be expected to have approximately the same effect on tacrolimus metabolism, even though we have found no such reports in the literature. Important to remember is that clinical consequences of amiodarone interactions may last for several months after discontinuation of amiodarone treatment, due to the slow elimination of the drug.

In the present case, as tacrolimus concentrations are monitored daily, it should be possible to adjust the dose accordingly. We also recommend that amiodarone concentrations be monitored.