Dose-Response Relationship Between Diltiazem and Tacrolimus and Its Safety in Renal Transplant Recipients

Abstract Background Inhibition of calcineurin inhibitor (CNI) metabolism with diltiazem reduces the dose of tacrolimus required to achieve its therapeutic blood concentration in kidney transplant recipients (KTRs). This cost-savings maneuver is practiced in several countries, including Malaysia, but the actual impacts of diltiazem on tacrolimus blood concentration, dose-response relationship, cost-savings, and safety aspects are unknown. Methods This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC 0 ) and other relevant clinical data for 70 eligible KTRs were reviewed. Results The dose of 1 mg tacrolimus resulted in a median TacC 0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC 0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus ( P 0 to 1.66 ± 2.58 ng/mL/mg tacrolimus ( P  = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC 0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [ P Conclusion Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC 0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.