HDCN Article Review/Hyperlink

Pesavento TE, Jones PA, Julian BA, Curtis JJ

Amlodipine increases cyclosporine levels in hypertensive renal transplant patients: results of a prospective study

J Am Soc Nephrol (Jun) 7:831-835 1996

Verapamil, diltiazem, and nicardipine, but not nifedipine, are known to interfere with cyclosporine metabolism and raise cyclosporine levels. The authors find that amlodipine also increased cyclosporine levels. In 11 patients studied prospectively, a 40% increase in cyclosporine levels was seen. When amlodipine was withdrawn, cyclosporine levels returned to baseline. Because of its long half life, steady state levels of amlodipine may not be achieved until 7-10 days after starting therapy, and the increase in cyclosporine levels may be delayed.

What is the mechanism whereby amlodipine causes an increase in cyclosporin levels? Presumably amlodipine is also metabolized by the cytochrome P-450 3A enzyme system in the liver, which is responsible for metabolism of cyclosporine. Interestingly, amlodipine i in the dihydropyridine class of CCBs, but not all dihydropyridines appear to affect cyclosporine levels. Nifedipine, isradipine, and nitrendipine apparently do not, while nicardipine and amlodipine do. Caution must be exercised particularly, when converting patients from long-acting nifedipine (which does not affect cyclo levels) to amlodipine (which does).

See also a related discussion on HDCN by Dr. George Aronoff pertaining to the P-450 enzyme system and cyclosporine . (John T. Daugirdas, M.D., University of Illinois at Chicago)