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Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. Results In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2021 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2021 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, coronavirus disease 2019 (COVID-19) pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2021 were based on a combination of quantitative analyses and expert opinion. Results In 2020, overall pharmaceutical expenditures in the United States grew 4.9% compared to 2019, for a total of $535.3 billion. Utilization (a 2.9% increase) and new drugs (a 1.8% increase) drove this increase, with price changes having minimal influence (a 0.3% increase). Adalimumab was the top drug in 2020, followed by apixaban and insulin glargine. Drug expenditures were $35.3 billion (a 4.6% decrease) and $98.4 billion (an 8.1% increase) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals the decrease in expenditures was driven by reduced utilization. Several new drugs that will influence spending are expected to be approved in 2021. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2021, we expect overall prescription drug spending to rise by 4% to 6%, whereas in clinics and hospitals we anticipate increases of 7% to 9% and 3% to 5%, respectively, compared to 2020. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

To determine whether the formation of a multidisciplinary team, pharmacist-led therapeutic interchange, and streamlined electronic health record optimization improved biosimilar adoption throughout Mayo Clinic.The project focused on the use of reference products and biosimilars for 5 biologics-bevacizumab, epoetin alfa, filgrastim, rituximab, and trastuzumab-at all Mayo Clinic locations. Pharmaceutical wholesale purchase histories of those reference products and biosimilars were assessed from September 1, 2020, through August 31, 2021, and compared with data from September 1, 2019, through August 31, 2020. Formulary decisions were implemented across 5 biologics for most ordering pathways on September 1, 2020. Pharmaceutical purchased drug units and expenditures were tracked at 3-month intervals for conversion to formulary-preferred contracted biosimilars.In the final postimplementation period, the absolute percentage increase of formulary-preferred biosimilars was 69% for bevacizumab, 63% for epoetin alfa, 80% for filgrastim, 79% for rituximab, and 72% for trastuzumab. Pharmaceutical line item savings in the 12-month postimplementation period totaled $23.1 million across all 5 biologics.Creation of a multidisciplinary team to implement formulary-preferred contracted biosimilars led to the adoption of biosimilars throughout Mayo Clinic with considerable pharmaceutical line item savings.

Immunoglobulin G (IgG) is a commonly used treatment for chronic neuromuscular disorders (NMDs), such as chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. IgG therapy has also shown promise in treating other NMDs including myasthenia gravis, polymyositis, and dermatomyositis. IgG is administered as either intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg), with SCIg use becoming more popular due to the treatment burden associated with IVIg. IVIg requires regular venous access; long infusions (typically 4-6 hours); and can result in systemic adverse events (AEs) for some patients. In contrast, SCIg can be self-administered at home with shorter infusions (approximately 1 hour) and fewer systemic AEs. As patient care shifts toward home-based settings, the role of the pharmacist is paramount in providing a continuation of care and acting as the bridge between patient and clinic. Pharmacists with a good understanding of current recommendations, dosing strategies, and administration routes for IgG therapy are best placed to support patients. The aims of this review are to highlight the evidence supporting IgG therapy in the treatment of NMDs and provide practical information on patient management and IVIg/SCIg dosing in order to guide pharmacists on optimizing clinical outcomes and patient care.

Objective Vancomycin, a commonly used antimicrobial, has a narrow therapeutic index; therefore, Therapeutic Drug Monitoring (TDM) is required. Although the Electronic Medical Record (EMR) may improve patient care, without appropriate optimization, it can contribute to incorrectly drawn vancomycin levels. For medication administration, nurses utilize the Medication Administration Record (MAR) for medication administration documentation and medication workflow guidance. Therefore, we hypothesized creating a MAR level order which would be incorporated into this already established medication workflow may improve the rate of correctly drawn vancomycin levels. Materials and Methods This was a multicenter, retrospective, pre-and post-intervention study which evaluated the effect of a Medication Administration Record (MAR) level order within the EMR on the correct timing of vancomycin level collection. Vancomycin levels were classified into pre-and post-intervention groups. The primary endpoint was the rate of incorrectly drawn levels, defined as a level being drawn early, a level being drawn late, a level drawn while infusing, or a missed level. Results A total of 1353 vancomycin levels were assessed, and 628 levels met inclusion criteria. Of the levels eligible for inclusion, 331 were in the pre-intervention period and 297 were in the post-intervention period. Levels in the post-intervention group utilizing the vancomycin MAR level order were less likely to be missed or drawn at an incorrect time (11.1 % vs 36 %, P Conclusion Utilization of a vancomycin MAR level order was associated with a significant decrease in incorrectly drawn vancomycin levels.

Purpose The pathophysiology, diagnosis, and medication-use implications of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzyme deficiency in humans, are reviewed. Summary Originally identified as favism in patients who experienced hemolysis after ingestion of fava beans, G6PD deficiency results from an X-linked chromosomal mutation that leads to reduced activity of the enzyme responsible for the final step of the pentose phosphate pathway, through which reduced nicotinamide adenine dinucleotide phosphate required for protection of cells from oxidative stress is produced. G6PD deficiency affects about 400 million people worldwide. Diagnosis of G6PD can be made through detection of enzymatic activity (by spectrophotometric testing, fluorescence testing, or formazan-based spot testing) or molecular analysis to detect known mutations of the gene encoding G6PD. Most individuals with G6PD deficiency are asymptomatic throughout life. Symptoms of acute hemolysis associated with G6PD deficiency include anemia, fatigue, back or abdominal pain, jaundice, and hemoglobinuria. The most common precipitators of oxidative stress and hemolysis in G6PD deficiency include medication use and infection. Conclusion G6PD deficiency should be considered in patients who experience acute hemolysis after exposure to known oxidative medications, infection, or ingestion of fava beans. A diagnosis of G6PD deficiency is most often made through enzymatic activity detection, but molecular analysis may be required in females heterozygous for the disorder. When clinically feasible, rasburicase, primaquine, dapsone, pegloticase, and methylene blue should not be used until a G6PD diagnostic test has been performed.

PurposeHistorical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2019 in nonfederal hospitals, clinics, and overall (all sectors).MethodsDrug expenditure data through calendar year 2018 were obtained from the IQVIA National Sales Perspectives database and analyzed. New drug approvals, patent expirations, and other factors that may influence drug spending in hospitals and clinics in 2019 were also reviewed. Expenditure projections for 2019 for nonfederal hospitals, clinics, and overall (all sectors) were made through a combination of quantitative analyses and expert opinion.ResultsU.S. prescription sales in calendar year 2018 totaled $476.2 billion, a 5.5% increase from 2017 spending. The top 3 drugs by expenditures were adalimumab ($19.1 billion), insulin glargine ($9.3 billion), and etanercept ($8.0 billion). Prescription expenditures in nonfederal hospitals totaled $35.8 billion, a 4.8% increase from 2017. Expenditures in clinics in 2018 increased by 13.0% to $80.5 billion. The increase in spending in nonfederal hospitals was largely driven by new products and increased utilization of existing products. The list of the top 25 drugs by expenditures in nonfederal hospitals and clinics was dominated by specialty drugs.ConclusionWe predict continued moderate growth of 4–6% in overall drug expenditures (across the entire U.S. market). We expect the clinic sector to continue to experience high (11–13%) growth in drug spending in 2019. Finally, for nonfederal hospitals we anticipate growth in the range of 3–5%. These estimates are at the national level. Health-system pharmacy leaders should carefully examine local drug utilization patterns to determine their own organization’s anticipated spending in 2019.

Background The cytomegalovirus (CMV) donor-positive/recipient-positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate-risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head-to-head analysis comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs. 900 mg/day for 3-months in D+/R+ RTR. Methods A multicenter, retrospective analysis evaluated 478 adult RTR between 01/2008 and 10/2011. Study participants received VGCV 450 mg/day (Group 1; n = 398) or 900 mg/day (Group 2; n = 89) x 3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months. Results The rates of graft loss, patient survival, T-cell and/or antibody mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups. Conclusion The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs. 3.4%; P = 1.000). Log-rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P = 0.939). This article is protected by copyright. All rights reserved.

Purpose The implementation and outcomes of a pharmacist career ladder program (PCLP) at a tertiary care, academic medical center are described. Summary A PCLP was developed at Yale-New Haven Hospital to guide career development, motivate staff to perform beyond their daily tasks and responsibilities, and recognize and retain high performers through professional advancement. The PCLP advancement criteria include specific requirements for excellence in five categories: level of training and experience, pharmacy practice, drug information, education and scholarship, and leadership. The PCLP is designed with four distinct tiers: clinical pharmacist, clinical pharmacist II, clinical pharmacy specialist, and clinical pharmacy specialist II. The specific criteria are increasingly challenging to achieve when moving up the ladder. Pharmacists may apply voluntarily each year for advancement. A PCLP review committee consisting of pharmacist peers and managers meets annually to discuss and vote on career advancement decisions. Since PCLP implementation, we have observed an increasing success rate for advancement (50% in 2013, 85% in 2014, and 100% in 2015) and a considerable increase in pharmacist participation in clinical and process improvement projects, as well as intervention and medication-use variance documentation. Conclusion The implementation of a PCLP at a tertiary care, academic medical center provided an opportunity for frontline pharmacists to advance professionally and increased their participation and leadership in clinical and process improvement projects and drug-use policy and medication safety initiatives; the program also increased the number of pharmacists with specialty board certification and peer-reviewed publications.

Benefits of belatacept-based immunosuppressive regimens in human immunodeficiency virus (HIV)-positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new-onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV-positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV-positive renal transplant recipient.

Nonadherence to therapy remains a principal challenge in optimizing long-term graft survival in solid organ transplant recipients. The consequential outcomes of rejection, graft loss, and survival due to nonadherence are reported primarily from studies of renal transplant recipients; outcomes data

Hyperuricemia is a common comorbid condition experienced by up to 28% of kidney transplant recipients. These patients are at elevated risk of acute flare-ups of gout because of transplant-specific risk factors such as impaired renal function, chronic contributing pharmacotherapy (eg, calcineurin inhibitors, diuretics), and associated comorbid conditions. After transplant, treatment is often complicated by drug-drug interactions, renal impairment, and toxic effects of drugs with the use of first-line recommended agents. A number of therapeutic options remain available for transplant recipients, including dose modifications of historic agents and newer pharmacotherapeutic options. Notably, the Kidney Disease Improving Global Outcomes guidelines address the management of hyperuricemia and gout, but these guidelines were last published in 2009, and new data and treatment options have emerged since then. The management of hyperuricemia and acute and chronic gout is described, including the use of novel agents including urate oxidases, interleukin 1 inhibitors, and human urate transporter 1 inhibitors and alternative immunosuppressive therapy strategies.

Purpose Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. Summary The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patient’s mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme–mediated drug interactions, (3) mental health–related medication use, (4) chronic pain–related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. Conclusion Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented.

Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.

The American Society of Health-System Pharmacists’ Pharmacy Practice Model Initiative (PPMI) aims to develop and disseminate pharmacy practice models that optimize the use of pharmacists as direct care providers.1 In their commentary, Jacobi and colleagues highlight opportunities and challenges presented through the PPMI, and draw attention to potential negative consequences for clinical pharmacy specialists.2 We present the transplant specialist perspective. This article is protected by copyright. All rights reserved.

Pharmacists have been part of the multidisciplinary transplantation care team for more than four decades. The first article detailing the pharmacist’s role on the transplantation team was published in this journal in 1976.[1][1] Since the 1970s, a pharmacist’s presence within the transplantation

Purpose The safety of converting kidney transplant recipients on brand-name tacrolimus to generic tacrolimus during hospitalization was evaluated. Methods A single-center observational study compared tacrolimus dosages and trough tacrolimus levels in kidney transplant recipients who had a kidney transplant more than 90 days before hospital admission. Patients in the “brand” group were maintained on brand-name tacrolimus throughout the entire study period. Patients in the generic group were maintained on brand-name tacrolimus before hospital admission, converted to the generic formulation during hospitalization, and returned to the brand-name product at discharge. Tacrolimus dosages were converted on a milligram-per-milligram basis and adjusted, if needed. Outcomes evaluated included the percentage of patients requiring a dosage change, absolute change in average tacrolimus trough level, and frequency of biopsy-proven acute rejection within six months of discharge. Results A total of 100 patients were evaluated for inclusion in the brand group, with 42 meeting study criteria; 98 patients were evaluated in the generic group, with 36 qualifying for the study. There were no significant differences between the brand and generic groups with respect to dosage adjustments required or trough tacrolimus levels at any point in the transition of care. Mean trough concentrations were similar between groups during all periods of care. The only occurrence of new-onset acute rejection within six months after admission occurred in the brand group. Conclusion Substitution of a generic formulation of tacrolimus for the innovator product during hospitalization of kidney transplant recipients was safely implemented. Tacrolimus dosage adjustments were common throughout the transitions of care, regardless of the formulation used.

Objective To review the components of the Congressional mandate for risk evaluation and mitigation strategies (REMS) managed by the Food and Drug Administration and assess their impact on health care providers practicing within the organ transplant arena. Data Sources and Extraction A non-date-limited search of MEDLINE and EMBASE (January 2007-June 2012) was conducted by using the following search terms: risk evaluation and mitigation strategies, REMS, and organ transplant, including a query of the individual organs. Information from the Federal Register and the Food and Drug Administration was also evaluated. Data Synthesis REMS are strategies implemented to manage known or potential risks associated with medications and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product. Elements of REMS programs may consist of 3 levels: a medication guide, communication plan, and elements to assure safe use. A medication guide is used to help prevent serious adverse events, aid in patients' decision making, and enhance medication adherence. Communication plans help educate health care providers and encourage adherence with REMS. The elements to assure safe use is a restrictive process implemented when it is deemed necessary to ensure safe access for patients to products with known serious risks. In transplant medicine, REMS currently exist for belatacept (medication guide and communication plan) and the mycophenolic acid derivatives (medication guide and elements to assure safe use). Conclusion REMS are another step in the evolution of the development and marketing of pharmaceutical agents. Use of REMS in solid-organ transplant is becoming common. Transplant clinicians must provide required patient education and become involved with other aspects of REMS implementation to reduce the serious risks of pharmaceuticals and to improve patients' outcomes.

Objective To review the elements and components of the risk evaluation and mitigation strategies (REMS) for the costimulation blocker belatacept and associated implications for health care providers working with transplant recipients. Data Sources and Extraction The MEDLINE and EMBASE databases (January 1990 to March 2012) were searched by using risk evaluation and mitigation strategies, REMS, belatacept, and organ transplant as search terms (individual organs were also searched). Retrieved articles were supplemented with analysis of information obtained from the Federal Register, the Food and Drug Administration, and the manufacturer of belatacept. Data Synthesis REMS are risk-management strategies implemented to ensure that a product's benefits outweigh its known safety risks. Although belatacept offers a novel strategy in maintenance immunosuppression and was associated with superior renal function compared with cyclosporine in phase 2 and 3 trials, belatacept is also associated with increased risk of posttransplant lymphoproliferative disorder and central nervous system infections. The Food and Drug Administration required development of a REMS program as part of belatacept's approval process to ensure safe and appropriate use of the medication and optimization of its risk-benefit profile. Conclusion—Elements of the belatacept REMS include a medication guide that must be dispensed with each infusion and a communication plan. In the management of a complex population of patients, it is essential that those who care for transplant recipients, and patients, recognize the implications of potential and known risks of belatacept. The REMS program aims to facilitate careful selection and education of patients and vigilant monitoring.

Introduction: There are several different agents that can be used for gastrointestinal (GI) ulcer prophylaxis in posttransplant recipients, such as histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPIs). Research Question: This study was conducted to compare the incidence of adverse kidney events in transplant recipients who received prophylaxis with H2RAs or PPIs. Design: This retrospective study included all kidney transplant recipients from 3 transplant centers who were transplanted in 2009 through 2011. The primary objective was to compare the incidence of adverse events posttransplant, defined as the incidence of pneumonia, Clostridium difficile, hip fractures, GI bleeding, cytomegalovirus, organ rejection, and bacteremia. Results: A total of 211 patients were included in the study; of which 35 were included in the PPI group and 176 were included in the H2RA group. There were no significant differences between groups in regard to incidence of GI bleeding events or other adverse events. Discussion: These findings suggest there is a low incidence of GI ulcers and upper GI bleeding events after kidney transplantation with the use of H2RAs or PPIs. Additionally, there are similar rates of adverse events when comparing H2RAs versus PPIs for GI ulcer prophylaxis.

Purpose Considerations for selecting an immune globulin treatment, transitioning patients with primary immune deficiency disease who are receiving long-term treatment between settings of care, and the role of the pharmacist in these endeavors are described. Summary Numerous immune globulin formulations are commercially available, and these formulations differ in immune globulin concentration, stabilizing additives, trace non–immune globulin proteins, and the manufacturing process, all of which may elicit different adverse reactions in patients. Patients may also exhibit differences in tolerability to the route of administration. The complex process of formulating, establishing, and maintaining an immune globulin treatment regimen requires the participation of the patient and healthcare providers. For patients transitioning between settings of care, particular attention must be paid to any changes to a treatment that has been individualized for a patient. Factors affecting the decision process include medical history, immune globulin formulation characteristics, formulary stock, payer formulary, and patient preference. For patients switching between immune globulin formulations or routes of administration, dosage adjustments of and tolerance to immune globulin may be important considerations. A clinical pharmacist with knowledge of the pharmaceutical suitability of immune globulin formulations can safely facilitate these transitions. Conclusion Selecting a route of administration for and formulation of immune globulin involves the consideration of many factors, including the patient’s medical history, formulation characteristics, formulary stock, payer formulary, and patient preference. A pharmacist is essential in helping the patient navigate the decision-making process and in coordinating care and communication among patients, caregivers, and healthcare providers to monitor patient progress and adherence and ensure safe and efficient transitions of care.

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.

AdV hepatitis is a rarely reported complication after pediatric liver transplantation that is associated with high rates of morbidity, mortality and graft failure. Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression. This report describes a case of AdV hepatitis in a pediatric liver transplant recipient successfully treated with a modified, renal sparing dosing of CDV.

Objective: To report the potential clinically significant pharmacokinetic interaction between sirolimus and dronedarone. Case Summary: A 67-year-old man status post-kidney transplant in 2004 was maintained on an immunosuppressive regimen consisting of sirolimus, mycophenolate mofetil, and prednisone. He had been maintained for more than 1 year on a stable dose of sirolimus (5 mg/day), with concentrations ranging between 5 and 13.5 ng/mL. The patient was admitted to the hospital with a complaint of bloody diarrhea; shortly after admission, he developed atrial fibrillation for which dronedarone 400 mg twice daily was initiated. Sirolimus concentrations obtained 3 days after initiation of dronedarone revealed a trough concentration that was increased by more than 3-fold (38.6 ng/mL) from his baseline trough concentration. After sirolimus was held for 6 days, the trough concentration was 7.8 ng/mL. The dosage was reduced to 1 mg/day; there was no need for further adjustment. Discussion: While the potential for an interaction between sirolimus and dronedarone is listed in the package insert of dronedarone, there are no documented reports of this interaction in the peer-reviewed literature. Since sirolimus is a narrow therapeutic index medication, information about the severity and magnitude of the interaction with dronedarone may help clinicians avoid therapeutic misadventures when this combination is employed. Our case clearly demonstrates a significant pharmacokinetic interaction between sirolimus and dronedarone. The Horn Drug Interaction Probability Scale indicates that the occurrence of an interaction between sirolimus and dronedarone in our case is probable. Conclusions: Due to the potential for sirolimus toxicity and excessive immunosuppression, the concurrent use of dronedarone and sirolimus should be avoided when possible. If concurrent administration cannot be avoided, we suggest close monitoring and a 50–75% dose reduction of sirolimus prior to dronedarone initiation.

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).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.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.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.

Purpose The pharmacologic properties of Rhesus (Rh) immune globulin (RhIG) and clinical data on its effectiveness in preventing Rh-antigen alloimmunization in pregnant women are reviewed. Summary RhIG is a human plasma derivative that targets red blood cells (RBCs) positive for RhO antigen (also called D antigen). In the United States and other countries, the widespread use of RhIG has markedly reduced the occurrence of hemolytic disease of the fetus and newborn (HDFN), a devastating condition caused by D-antigen sensitization of a pregnant woman via exposure to fetal RBCs (usually during detachment of the placenta in labor) that results in a maternal immune response leading to severe hemolysis in the fetus. Routine administration of RhIG at 26–30 weeks’ gestation and again within 72 hours of delivery has been shown to be highly effective in preventing maternal Rh alloimmunization, with very low rates of D-antigen sensitization (in the range of 0–2.2%) reported in multiple studies of at-risk women. The four RhIG products currently available in the United States have common clinical indications but differ in certain attributes. Pharmacists can play an important role in guiding other clinicians on the rationale for the use of RhIG, important differences between products, and appropriate timing of RhIG therapy. Conclusion Routine administration of RhIG to women at risk for Rh alloimmunization is clinically effective and has made HDFN a rare clinical event. The available RhIG products are not the same and should be carefully reviewed to ensure that they are administered safely.

Thrombocytopenia is a known complication of antiepileptic drug therapy. We present a case of a 3-year-old child who developed fever, rash, and severe thrombocytopenia within 10 days of initiating therapy with carbamazepine for new onset epilepsy. The patient's thrombocytopenia resolved following discontinuation of carbamazepine and introduction of valproic acid, however, his seizure disorder became poorly controlled. Phenobarbital was added to valproic acid therapy, which resulted in reoccurrence of fever, rash, and thrombocytopenia consistent with antiepileptic hypersensitivity syndrome. Discontinuation of phenobarbital, valproic acid and introduction of zonisamide resulted in resolution of his symptoms. The potential etiologies of thrombocytopenia in this case include carbamazepine-induced antiepileptic hypersensitivity syndrome, phenobarbital-induced antiepileptic hypersensitivity syndrome as a result of cross-reactivity with carbamazepine, and/or dose-dependent thrombocytopenia caused by valproic acid therapy. The pathogenesis and cases of aromatic anticonvulsant-induced immune-mediated thrombocytopenia are discussed. Alternative therapies for antiepileptic hypersensitivity syndrome with thrombocytopenia include gabapentin, levetiracetam, tiagabine, topiramate, and zonisamide.

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 $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $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.

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.

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 system's 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, belatacept's limited adverse-effect profile and convenient dosing strategy may make it an attractive option for immuno-suppressive maintenance for both the patient and clinician.

AdV hepatitis is a rarely reported complication after pediatric liver transplantation that is associated with high rates of morbidity, mortality and graft failure. Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression. This report describes a case of AdV hepatitis in a pediatric liver transplant recipient successfully treated with a modified, renal sparing dosing of CDV.

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