Description
Diltiazem inhibits CYP3A4-mediated tamsulosin metabolism, increasing tamsulosin plasma concentrations by up to 2-fold and heightening the risk of orthostatic hypotension and dizziness.
Mécanisme
Tamsulosin is metabolised by CYP3A4 and CYP2D6; diltiazem's CYP3A4 inhibition reduces tamsulosin clearance, increasing its AUC. Additionally, diltiazem has mild vasodilatory properties that may add to tamsulosin's alpha-1 blockade-induced hypotension.
Signification clinique
Pharmacokinetic studies confirm tamsulosin AUC increases of approximately 2-fold with diltiazem; case reports and spontaneous reports describe orthostatic hypotension and syncope.
Prise en charge
Use with caution; advise patients on fall precautions and orthostatic hypotension risk; consider reducing tamsulosin dose or monitoring blood pressure when diltiazem is initiated or dose-increased.