The expanded role of the transplant pharmacist: A 10-year follow-up.

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.

Overall Infectious Complications Related to Belatacept Conversion in Comparison to Tacrolimus in Kidney Transplant Recipients.

Introduction: Belatacept has demonstrated effectiveness for preventing rejection in kidney transplant and has a favorable side effect profile. Studies assessing long-term infectious complications with belatacept compared to tacrolimus are limited. Project Aims: The purpose of this program evaluation was to determine the proportion of patients who developed an infection when converted to belatacept compared to those on tacrolimus. Design: In this retrospective evaluation, kidney transplant recipients receiving belatacept were matched 1:1 to those receiving tacrolimus, based on transplant date, age, induction immunosuppression, and cytomegalovirus risk. Data collection was initiated in tacrolimus patients on the date of belatacept conversion in the belatacept-matched patients. Data were extracted until study conclusion, death, or discontinuation of belatacept. Patients were stratified into 3 groups based on time of conversion posttransplant, which included early, late, and very late conversion. The primary outcome was the proportion of patients with an infection in belatacept compared to tacrolimus. Outcome data were calculated using chi-square, Fisher's exact test, student's t-test or Mann-Whitney U test where appropriate. Results: A total of 328 matched patients were included in the analysis. More patients on belatacept developed an infection compared to tacrolimus (42.7% vs 29.9%, P = 0.02), which was primarily driven by pneumonia (6.1% vs 0.5%; P = 0.01). Higher incidences of infections were identified in those converted within 6 months from transplant. Conclusions: Belatacept was associated with a higher proportion of patients with infections compared to tacrolimus, particularly in those converted within 6 months from time of transplant.

Evaluating Potentially Inappropriate Medications in Older Kidney Transplant Recipients.

OBJECTIVES: Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) Criteria/Screening Tool to Alert to Right Treatment Criteria are used to assess potentially inappropriate prescribing and medications, which could pose a harm to those of older age. The purpose of this study was to assess and compare the use of Beers and STOPP Criteria in older kidney transplant recipients. METHODS: This was a dual-center, retrospective chart review from May 1, 2014, to March 1, 2018, including kidney transplant recipients 65 years and older. Those who underwent a dual transplant or had incomplete medical records were excluded. Outcomes included number of potentially inappropriate medications (PIMs) comparing Beers and STOPP Criteria on transplant admission, number of PIMs on admission compared with discharge, and readmissions within 3 months related to these medications. RESULTS: A total of 121 recipients were evaluated. On admission, 60 medications were listed on the STOPP Criteria compared with 106 medications on the Beers Criteria. When comparing PIMs on admission to discharge, there was a 38% decrease in the number of medications on discharge using the STOPP Criteria, whereas there was a 9% increase using the Beers Criteria. CONCLUSIONS: Older recipients were more likely to be on a medication listed in the Beers Criteria on admission and have a new medication listed in the Beers Criteria upon discharge compared with the STOPP Criteria.

Impact of Low-Dose Fluconazole on Tacrolimus Dosing in Renal Transplant.

BACKGROUND: The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use. OBJECTIVE: This study quantified the drug interaction between low-dose fluconazole (LDF) and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients. METHODS: We conducted a single-center retrospective chart review of renal transplant patients >18 years who received LDF or nystatin (NYS), and TAC. The primary outcome was the difference in tacrolimus total daily dose (TAC TDD) for LDF versus NYS groups. Secondary outcomes included days with supratherapeutic, therapeutic and subtherapeutic tacrolimus levels, time to therapeutic level, incidence of adverse drug reactions and graft rejection. RESULTS: We evaluated 94 patients and included 81. Low-dose fluconazole received a greater TAC TDD prior to post-operative day (POD) 10 (10.5 ± 4.7 mg vs. 7.1 ± 4.5 mg, p < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 ± 2.2 mg vs. 9.8 ± 0.8 mg, p < 0.001) and following LDF discontinuation (6.9 ± 0.1 mg vs. 9.0 ± 0.4 mg, p < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 ± 7.0 vs. 13.9 ± 8.5; p = 0.02) but fewer with subtherapeutic (6.7 ± 5.7 vs. 12.9 ± 7.2; p < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 ± 5.8 vs. 14.4 ± 6.6, p = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 ± 2.7 vs. 11.5 ± 7.7; p < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection. CONCLUSION: A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels.

A Pharmacist-Driven Intervention Designed to Improve Medication Accuracy in the Outpatient Kidney Transplant Setting.

BACKGROUND: Medication errors are one of the leading causes of complications and readmissions in healthcare and stem directly from inadequate medication lists. In transplantation, medication discrepancies can lead to fluctuating levels of immunosuppression, resulting in rejection, infection, or drug toxicity. METHODS: We implemented a pharmacist-driven intervention designed to improve the accuracy of outpatient kidney transplant patients' medication lists in the electronic medical record (EMR). Baseline medication error rates (Phase 1) were collected, and the intervention was a dedicated pharmacist (Phase 2) who performed medication reconciliation with patients. The primary outcome was the percent of patients with inadequate medication reconciliation determined by any one error in medication reconciliation (Phase 1 vs Phase 2). Secondary outcomes included the number of medication errors, of all medications and high-risk medications, identified per patient sample using statistical process control phase analysis. RESULTS: Pharmacist-driven medication reconciliation significantly reduced medication list discrepancies from 95% to 28% (P<0.05). There were a total of 398 errors in the control group and 49 errors in the intervention group. In addition, there were 73 high-risk medication discrepancies in the control group and three in the intervention group. The total number of medication errors decreased post-intervention with a marked reduction in the variation of control limits (LCL, UCL: phase 1, -34.3, 113.9; phase 2, -7.1, 15.3) and average number of medication errors per sample (phase 1, 39.8; phase 2, 14.1). For high-risk medications, phase analysis demonstrated a marked reduction in control limit variation between phases (LCL, UCL: phase 1, -10.4, 25.0; phase 2, -0.5, 0.7) and average number of medication errors per sample (phase 1, 7.3; phase 2, 0.1). DISCUSSION: A dedicated pharmacist improved medication list accuracy over conventional practice that utilizes transplant nurses and physicians. Further studies into the cost-effectiveness of this strategy should further justify this approach.

Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability-Does One Exist?

The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how Severe Acute Respiratory Syndrome 2 virus (SARS-CoV-2) may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. METHODS: Without prior knowledge of how this virus would affect our transplant center's delivery of care to KTRs who are SARS-CoV-2 positive or patients under investigation, and in the setting of limited testing availability, we initiated a quality assurance and improvement project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. RESULTS: Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without a history of BKV (80% and 28%, respectively; P = .002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (P = .06).

Chronopharmacokinetics and Food Effects of Single-Dose LCP-Tacrolimus in Healthy Volunteers.

BACKGROUND: A modified-release version of tacrolimus, LCP-tacrolimus (LCPT; Envarsus XR, Veloxis Pharmaceuticals, Cary, NC), has been licensed in the United States for prophylaxis of organ rejection in de novo kidney transplant patients. As tacrolimus has a narrow therapeutic window, the impact of circadian patterns on LCPT drug exposure, including food and chronopharmacokinetic effects, needs to be elucidated to optimize dosing. METHODS: Two randomized, crossover, phase 1 studies were conducted in healthy volunteers. The first assessed the effect of morning versus evening dosing on the pharmacokinetic profile of LCPT 2 mg; the second assessed the effect of food on the pharmacokinetic profile of LCPT 5 mg. In both, blood samples were drawn from participants for up to 144 hours after administration of a single LCPT dose. RESULTS: No significant differences were observed between evening and morning dosing in peak blood concentration (4.4 versus 4.0 ng/mL; P = 0.27), area under the time-concentration curve (AUC) from time 0 to time of the last concentration (89.1 versus 102.6 ng/mL; P = 0.20), AUC from time 0 to infinity (99.7 versus 114.3 ng·h/mL; P = 0.18), AUC from 0 to 24 hours post-dose (AUC0-24; 49.4 versus 51.6 ng·h/mL; P = 0.56), time to reach maximum blood concentration (median, 6.0 versus 6.0 hours; P = 0.91), total clearance (arithmetic mean = 21.5 versus 19.5 L/h; P = 0.50), or terminal half-life (arithmetic mean = 26.8 versus 28.1 hours; P = 0.26). After a high-calorie meal in the morning, the AUC0-24 reduced by 54% (ratio of geometric means = 45.6%; P < 0.0001) and peak blood concentration reduced by 22% (ratio of geometric means = 78.4%; P = 0.0006). However, the terminal half-life did not differ between fasted and fed states (33.3 versus 34.8 hours; P = 0.16), implying that these differences occurred because of altered bioavailability rather than modified clearance. CONCLUSIONS: For LCPT, no chronopharmacokinetic effects were observed, whereas food significantly reduced the 24-h exposure and the peak blood concentration.

Listeria monocytogenes bacteremia in a pancreas transplant recipient.

We report a case of Listeria monocytogenes bacteremia in a patient 12 years after his pancreas transplant, during which time he received a steroid-free immunosuppressive regimen. To our knowledge, there are no reported cases describing L monocytogenes bacteremia after pancreas transplant. In addition, although typically identified as a complication shortly after transplant or after treatment for organ rejection, this case demonstrates that it is still possible for a patient to develop a L monocytogenes infection far removed from transplant.