Eric M. Tichy

A multicenter experience with generic tacrolimus conversion.

Background. The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Methods. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Results. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were

Evolution of the Role of the Transplant Pharmacist on the Multidisciplinary Transplant Team

645 for brand,

Belatacept: A Novel Biologic for Maintenance Immunosuppression After Renal Transplantation

593 for generic, and

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.

595 for generic after dose titrations. Mean monthly patient copays were

Call for Antimicrobial Stewardship in Solid Organ Transplantation

38 for brand and

Significant Sirolimus and Dronedarone Interaction in a Kidney Transplant Recipient

15 for generic. Conclusions. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

Belatacept and Eculizumab for Treatment of Calcineurin Inhibitor-induced Thrombotic Microangiopathy After Kidney Transplantation: Case Report

Transplant pharmacists have been recognized as an essential part of the transplant team by their colleagues along with several governing and professional organizations. The specific education, training and responsibilities of the transplant pharmacist have not been clearly delineated in the literature. Various pharmacists across the country have been called upon to serve on the transplant team necessitating standardization of their fundamental and desirable activities. Therefore, the purpose of this manuscript is to describe the training and role of a transplant pharmacist on the patient care team and provide a roadmap to implementation of novel transplant pharmacy services.

Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients

In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long‐term use in renal transplant recipients. The costimulatory pathway (signal 2) of T‐cell activation and proliferation is produced by stimulation of the T‐cell surface marker, CD28, and is essential to the immune systems cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7–1 (CD80) and B7–2 (CD86) ligands present on antigen‐presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living‐ and deceased‐donor renal transplants, as well as in patients receiving kidneys transplanted from extended‐criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy‐proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin‐based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein‐Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long‐term risks of belatacept are needed to better define its role as immunosuppressive maintenance therapy. Aside from an increased risk of malignancy, belatacepts limited adverse‐effect profile and convenient dosing strategy may make it an attractive option for immuno‐suppressive maintenance for both the patient and clinician.

Assessing pharmacologic and nonpharmacologic risks in candidates for kidney transplantation.

Background Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Methods Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Results Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211–0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Conclusions Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.

Risk Evaluation and Mitigation Strategies: A Focus on Belatacept:

To the Editor:We read with interest the recently published InfectiousDisease Guidelines of the American Society of Transplan-tation (AST), and commend the Infectious DiseasesCommunity of Practice for the timely release of thesecomprehensive guidelines (1). We are disappointed,however, to see that a cohesive approach to developingan antimicrobial stewardship program (ASP) within thetransplant community was not described. ASPs can have apositive impact on limiting the prevalence of multidrugresistant (MDR) infections, a focus of several of the newguidelines. Transplant recipients are disproportionatelyaffected by MDR bacteria, with prolonged exposure tobroad-spectrum antimicrobial agents often present as thesole risk factor for their development (2).Numerous studies have shown that various stewardshipinterventions are able to decrease inappropriate use ofantimicrobialsandlimittheriseofresistantbacteriawithoutaconcomitant decline in clinical outcomes (3). While theimpact of ASPs in a transplant-specific population has notbeen formally evaluated, hospital-level and multicenterstudies evaluating the impact of ASPs frequently includesolid organ transplant recipients as part of their targetpopulation. Additionally, the benefit of ASPs in limiting therise of MDR bacteria may extend as collateral benefit totransplant patients, as admission to rooms that werepreviouslyoccupiedbypatientscolonizedwithMDRbacteriahas been shown to be an independent risk factor for theacquisition of MDR bacteria by subsequent patients (4).The Infectious Diseases Society of America, Society forHealthcare Epidemiology of America and Pediatric Infec-tious Diseases Society have recently released a positionstatement calling for mandatory implementation of ASPsthroughout the healthcare system (5). We believe that thetransplant community is a key stakeholder in this mandate,serving a patient population that is likely to derive thegreatest benefit from its implementation. Through formalguidance and recommendations to its members on theimplementation of antimicrobial stewardship, we believethat AST can have a lasting, positive impact on the well-being of the patients it serves. We call upon AST to adoptcomprehensive guidelines for antimicrobial stewardship tofurther this goal.S. L. Aitken