Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients. Available antivirals are fraught with adverse effects and risk for the development of CMV resistance. Letermovir is a novel antiviral in the late stages of drug development for the treatment and prevention of CMV. Areas covered: A MEDLINE search of the MeSH terms 'letermovir,' 'cytomegalovirus,' 'hematopoietic stem cell transplant,' and 'solid organ transplant,' was last conducted on 15 August 2016. Articles were selected on the basis of their contribution to current knowledge about letermovir. Expert opinion: Letermovir's mechanism of action, pharmacokinetic and pharmacodynamic profile, and favorable efficacy and safety make it an attractive option for both the prevention and treatment of CMV in immunocompromised patients. The lack of cross-resistance with other antivirals and the absence of myelosuppression are two prominent characteristics of letermovir that could support broad use of this product following FDA-approval. One major limitation is its lack of activity against other herpesviruses, which are commonly seen in immunocompromised hosts. We believe that with additional clinical efficacy data, this medication could emerge as a primary option for the prevention and treatment of CMV in the immunocompromised patient population.
Tacrolimus is an immunosuppressant that exerts its activity via suppression of cellular immunity by binding to FKBP-12 to form a complex with calcineurin-dependent proteins to inhibit calcineurin phosphatase activity and subsequently T lymphocyte activation. Approved by the Federal Drug Administration (FDA) under the brand name Prograf ® in 1994, immediate-release tacrolimus (IR-TAC) is now considered the backbone of maintenance immunosuppressive regimens in solid organ transplantation (SOT). In the United States (US), it is reported that more than 70% of SOT recipients are initiated on a TAC-based regimen (SRTR 2018 Annual Report). The extensive use of tacrolimus is likely attributable to its superiority in prevention of allograft rejection, particularly in the
Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.
Introduction The contributions of transplant pharmacists to clinical and translational research in the United States are ill‐defined and have not been systematically reviewed. Objectives The American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network conducted a systematic review of available pharmacist‐led research publications involving solid organ transplantation with the intent to quantify and describe pharmacist‐led research endeavors and their changes over time. Methods An electronic search of Scopus was conducted to identify publications in the field of solid organ transplantation by pharmacist authors between January 1, 1975 and May 25, 2017. Articles were excluded if they were written in non‐English languages or originated from non‐US countries. Review articles, case reports, surveys, basic science research, pre‐clinical studies, and non‐transplant research were further excluded. Studies were categorized as one of four phases on the clinical and translational research spectrum, adapted from the Harvard Clinical and Translational Science Center description of a T1 to T4 classification system. Results A total of 10 354 publications were identified by the systematic search with 547 full‐text English‐language publications included in the analysis. Pharmacists served as the first author in 87% of the articles and as the senior author in 67% of the articles. A total of 71% of the articles included more than one pharmacist author. Transplant pharmacists published more studies that employed a retrospective or observational study design (55% and 78%, respectively). A total of 37% of studies were funded. On the spectrum of clinical and translation research, pharmacists were most involved in T3 (translation to practice) research (72%), followed by T2 (translation to patients) research (23%). Conclusions Transplant pharmacists are increasingly represented in the US literature and frequently published across domains. Further demonstrating the relevance of pharmacist‐delivered interventions and outcomes is a critical area of practice focus.
The pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life‐sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non‐pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug‐drug interactions with popular weight management products.
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