Tacrolimus Toxicity Due to Drug Interaction with Mibefradil in a Patient After Liver Transplantation

A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 ng/ml) until recently, revealed an increase to toxic level of 54 ng/ml. After discontinuation of mibefradil, tacrolimus levels returned to the normal range and all symptoms and clinical changes were reversible. Mibefradil and tacrolimus both are metabolized through the cytochrome--P-450 pathway. We suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by mibefradil was responsible for these toxic effects. Therefore, special caution is recommended when administering tacrolimus with other drugs that carry the potential for pharmakokinetic interaction.