Moderate
Established
描述
Diltiazem inhibits CYP3A4 and P-glycoprotein, increasing tacrolimus blood concentrations by 40–70% and heightening the risk of dose-related tacrolimus toxicity.
机制
Diltiazem reversibly inhibits intestinal and hepatic CYP3A4 and P-gp, reducing tacrolimus first-pass metabolism and increasing its systemic bioavailability.
临床意义
Prospective pharmacokinetic studies in transplant recipients demonstrate that diltiazem co-administration requires tacrolimus dose reductions averaging 30–50% to maintain target troughs.
处理措施
Reduce tacrolimus dose when diltiazem is initiated; monitor trough levels every 3–5 days until stable, then per usual schedule; re-adjust upon diltiazem discontinuation.