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.

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.

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

Transplant immunosuppressants are often used off-label because of insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.

Despite advances in the field of transplantation, immunosuppressant medication nonadherence (NA) remains a primary contributor to suboptimal long-term outcomes. Due to the multidimensional and multifactorial causes of medication NA, studies to date have focused on individual differing facets or single point barriers of NA with relative success. However, these successes have not proven to be sustainable, partly due to the intense resources needed for continued viability. This article provides a summary of a 2-day meeting held in April 2017 (Chicago, IL) prior to the American Transplant Congress in which a multidisciplinary group convened to identify the unmet research needs related to medication NA in transplantation. Thought leaders in the field presented the past, present, and future directions of medication NA with the primary outcome of designing, developing, and ranking targeted interventions into a dynamic research agenda to identify which interventions maintained effects over time. Break-out sessions were created based on the five World Health Organization (WHO) dimensions of adherence. Participants were then organized into the newly formed AST Transplant Pharmacy Adherence Consortium (AST TPAC) research group. This meeting report summarizes the content of the symposium, and the development, background, and future directions of the AST TPAC.

We respectfully disagree with some points voiced in Dr. Klintmalm's editorial regarding generic immunosuppression (1).(1) Regardless if a generic or brand immunosuppressant is used, significant variation in calcineurin inhibitors' trough concentrations must be considered in the context of patient-specific therapeutic ranges. For example, a 25% fluctuation in tacrolimus trough concentrations in a patient whose target is 4-6 ng/mL may not be considered as clinically significant as the same percent change in a patient whose target is 8-12 ng/mL. Moreover, intrasubject variability in exposure to calcineurin inhibitors is commonplace in patients maintained on innovator products. These pharmacokinetic variations are secondary to: impact of food on drug exposure, fluctuations in renal and/or hepatic function, alterations in administration times and timing of trough levels. Although the inception of generic immunosuppressants introduces one additional variable, the clinical significance of this variable is not well defined. (2) Misinformation continues to be disseminated regarding the interpretation of confidence interval (CI) bioequivalence testing (1,2). In order for a generic medication to be considered bioequivalent, the 90% CI of the geometric, not arithmetic, mean of the ratio of the generic compared to the innovator product of the maximum concentration and area under the curve (AUC) values must lie between 80% and its reciprocal, 125% (3). In contrast to an arithmetic mean, which represents the midpoint of the range of values, a geometric mean mutes the contributing effect of extreme low and high values, respectively. If the true (arithmetic) mean exposure of a generic approaches ±20%, then one or both of the 90% CI is likely to fall outside the bioequivalence limits (4). The actual mean differences of four Food and Drug Administration (FDA)-approved tacrolimus generics in healthy volunteers is 4% (range 0-11%) for AUC fasting and 4.5% (2-6%) for AUC fed. (3) The degree of cost savings associated with generic immunosuppressants, and the benefactor of that savings, is multifactorial. For example, a patient's copay will vary depending on the type of billable insurance they possess (private vs. federally funded Medicare Part B or D vs. state funded Medicaid) and may change throughout the year (5). We agree that savings associated with the use of generic immunosuppressants should be countered by the associated cost of increased laboratory monitoring.We acknowledge that further research is necessary to determine the pharmacoeconomic impact of generic immunosuppressants. Future studies performed in transplant recipients will help answer these questions, as well as provide pharmacokinetic data comparing innovator to generic immunosuppressive products. Currently the FDA is considering potential refinements in bioequivalence criteria for narrow therapeutic index drugs and we expect that selective immunosuppressant agents will be included in this new classification. Transplant clinicians can advocate for policy changes reg...

This work extends previous studies exploring how undergraduate science students apply their classroom biology knowledge to everyday phenomena—in this case, genetically modified organisms (GMOs). Also described are how intuitive ways of thinking might underlie misconceptions that interfere with students applying their biology knowledge to GMOs.

A novel coronavirus has had global impact on individual health and health care delivery. In this C4 article, contributors discuss various aspects of transplantation including donor and recipient screening, management of infected patients, and prevention of coronavirus disease (COVID). Donor screening with SARS‐CoV‐2 nucleic acid testing (NAT) close to the time of procurement is recommended. Many programs are also screening all potential recipients at the time of admission. The management of COVID has evolved with remdesivir emerging as a new potential option for transplant recipients. Dexamethasone has also shown promise and convalescent plasma is under study. Prevention strategies for transplant candidates and recipients are paramount. Pediatric‐specific issues are also discussed. Strategies for the psychological well‐being of patients and providers are also imperative, in addition to future research priorities for transplantation.