Concomitant calcium supplementation does not compromise immunosuppressive dosing in kidney transplant recipients

Background Polypharmacy following kidney transplantation entails a risk of both drug–drug interactions (DDIs) and reduced patient adherence. Co‐administration of calcium supplementation and mycophenolate mofetil (MMF) has previously been shown to influence pharmacokinetics (PK) of MMF. In current DDI databases, there is a recommendation for 2‐ to 3‐h time‐shifted administration. Whether a similar interaction potentially exists for tacrolimus has not been evaluated. We aimed to investigate the potential PK DDI between co‐administrated calcium/vitamin D supplementation and the immunosuppressive drugs MMF and tacrolimus, using volumetric absorptive microsampling (VAMS). Methods Twenty‐five kidney transplant recipients on stable MMF, tacrolimus and prednisolone treatment provided two 12‐h PK investigations of simultaneous assessment of both mycophenolic acid (MPA) and tacrolimus concentrations. One PK investigation with and one without concomitant treatment with a calcium/vitamin D supplement. Capillary blood samples using VAMS were utilized to obtain samples in a patient friendly manner. Clinically relevant interactions were assessed by the with/without ratio of AUC 0–12 and C max in accordance with EMA bioequivalence guidelines. Results The MPA AUC 0–12 ratio was 0.94 (90% confidence interval [CI], 0.83–1.07) and the C max ratio was 0.79 (90% CI, 0.65–0.97). For tacrolimus, the AUC 0–12 and C max ratios were 1.00 (90% CI, 0.92–1.09) and 0.96 (90% CI, 0.87–1.07), respectively. Conclusion In kidney transplant recipients there is no clinically relevant PK DDI caused by concomitant administration of calcium/vitamin D supplementation with MMF and tacrolimus. Based on these observations, recommendation of time‐shifted administration of calcium supplements and immunosuppressive drugs seems unnecessary.