Описание
Diltiazem inhibits CYP3A4 and P-glycoprotein, increasing tacrolimus blood concentrations by 40–70% and heightening the risk of dose-related tacrolimus toxicity.
Механизм
Diltiazem reversibly inhibits intestinal and hepatic CYP3A4 and P-gp, reducing tacrolimus first-pass metabolism and increasing its systemic bioavailability.
Клиническое значение
Prospective pharmacokinetic studies in transplant recipients demonstrate that diltiazem co-administration requires tacrolimus dose reductions averaging 30–50% to maintain target troughs.
Тактика ведения
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.
Медицинский отказ от ответственности
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