Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers.

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.

A retrospective analysis of the safety and efficacy of apixaban use after lung transplant.

Direct acting oral anticoagulants (DOACs) have become the mainstay of treatment for patients requiring anticoagulation for atrial arrhythmias and venous thromboembolism (VTE) but safety and efficacy has not been established in lung transplantation. This is a retrospective review of 28 adult lung transplant patients who were prescribed apixaban for stroke prevention in atrial arrhythmias or treatment of VTE between October 15, 2015 and December 31, 2018. The primary outcome was a composite of efficacy and safety measured by recurrence or breakthrough of stroke or thromboembolism and bleeding events. Seven patients were treated for atrial arrhythmias and 21 treated for VTE. Fifteen patients received CYP3A4 or P-gp inhibitors at initiation of anticoagulation, and 4 of these patients received strong CYP3A4 inhibitors. During the follow-up period, one breakthrough DVT and one clinically relevant non-major bleed were observed. These data suggest that apixaban may be safe to use for lung transplant patients, and larger studies are warranted to assess long-term outcomes as well as safety and efficacy of alternative DOACs.