Açıklama
Concurrent use of cyclosporine and tacrolimus dramatically amplifies nephrotoxicity and is generally contraindicated; both agents independently cause renal vasoconstriction and tubular injury.
Mekanizma
Both calcineurin inhibitors reduce renal afferent arteriolar blood flow through increased thromboxane A2 and endothelin-1 production and decreased prostacyclin; the combination produces additive/synergistic renal vasoconstriction. Additionally, cyclosporine inhibits CYP3A4 and P-gp, raising tacrolimus levels.
Klinik Önemi
Transplant registries report significantly higher rates of acute kidney injury and chronic allograft nephropathy when both CNIs are co-administered, even briefly.
Yönetim
Concurrent use is contraindicated in most transplant protocols; if transitioning from cyclosporine to tacrolimus, allow a 24-hour washout before starting tacrolimus and monitor renal function closely.