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 ons et as well as shoulder muscle ache. In addition, reversible impairment of r enal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 n g/ml) until recently, revealed an increase to toxic level of 54 ng/ml. Afte r discontinuation of mibefradil, tacrolimus levels returned to the normal r ange and all symptoms and clinical changes were reversible. Mibefradil anti tacrolimus both are metabolized through the cytochrome-P450 pathway. We suspect that drug intel action duct to competitive inhibition of tacrolimus metabolism by mibefradil was responsible fur these toxic effe cts. Therefore, special caution is recommended when administering tacrolimu s with other drugs that carry the potential for pharmakokinetic interaction .