P1770HIGH PILL BURDEN INCREASES INTRAPATIENT TACROLIMUS TROUGH LEVELS VARIABILITY IN STABLE KIDNEY TRANSPLANT RECIPIENTS

Abstract

Abstract Background and Aims High intrapatient variability (IPV) of tacrolimus trough levels is associated with poor long-term outcome after transplantation. Polypharmacy, related to the high co-morbidity, may affect the pharmacokinetics of tacrolimus in a substantial proportion of kidney transplant recipients (KTRs). We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. Method We studied 152 tacrolimus-treated KTRs with mean post-transplant time 6.0±3.1 years, without dosing changes over the consecutive 2 years. The coefficient of variation (CV) as a measure IPV was calculated in each patient. Data concerning the type (generic name) and number of currently prescribed medications were collected. The participants were divided into 4 groups, based on the number of regularly prescribed drugs (≤3; 4-6; 7-9; ≥10). Results The median daily pill burden was 6.2±2.5 (ranged 2 to 15). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (IQR 0.08-0.14); group 2: 0.14 (0.01-0.17); group 3: 0.17 (0.14-0.23); group 4: 0.17 (0.15-0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503; p<0.001], age [rpartial = -0.150; p=0.07] and eGFR [rpartial = -0.140; p=0.09] independently influenced the tacrolimus IPV (R2=0.30). Concomitant steroids or diuretics use increased IPV only in Advagraf-treated KTRs, whereas PPIs or statin use increased IPV in Prograf, but not Advagraf group. Conclusion: The number of medications is positively associated with tacrolimus IPV in stable KTRs. There were also tacrolimus formulation-dependent differences in the assumed influence of several concomitantly received classes of medications, including steroids, diuretics, PPIs and statins, on the tacrolimus IPV.