Comparison of the Effects of Intravenous and Oral Tranexamic Acid on Perioperative Hemoglobin Levels During Total Knee Arthroplasty.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent shown to reduce perioperative blood loss in patients undergoing total knee arthroplasty (TKA), but there are limited data regarding the efficacy of intravenous (IV) in comparison to oral (PO) TXA. Objective: The purpose of this research was to compare the effects of IV and PO TXA on perioperative hemoglobin (Hgb) levels in patients who have undergone TKA. Methods: In this single-center, retrospective chart review, patients at least 18 years of age who received IV or PO TXA following medical center protocol from 1 of 3 orthopedic surgeons were included. The primary outcome was the change in Hgb within 24 hours following TKA. Secondary outcomes included comparisons of postsurgical complications and hospital length of stay. Results: The IV TXA group contained 62 participants, and the PO TXA group contained 61 participants. Patients receiving PO therapy had a larger decrease in Hgb compared with the IV TXA group (-2.382 vs -1.908, P = 0.02), but there were no statistically significant differences in mean length of stay (3.13 vs 2.95, P = 0.27), venous thromboembolism (VTE) occurrence (0 vs 0, P = 1), or requirement for transfusions (6 vs 5, P = 0.76). Conclusions and Relevance: IV and PO TXA may not be equivalent in outcomes for patients undergoing TKA. This study found a statistically significant decrease in the mean change of Hgb in patients receiving PO TXA compared with IV TXA. However, the rate of transfusions, mean length of stay, and rate of VTE were similar between groups.

Nebulized Tranexamic Acid for the Use of Epistaxis: A Case Report.

BACKGROUND: Tranexamic acid is an antifibrinolytic agent and functions as a competitive inhibitor of plasminogen activation, promoting hemostasis. Topical application of tranexamic acid for the control of epistaxis has been described in the literature, mainly through administration with gauze and packing. There is limited evidence for the use of tranexamic acid via alternative routes of administration such as nebulization. CASE REPORT: We describe a patient who presented to the emergency department with epistaxis who was treated with nebulized tranexamic acid. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case provides an alternative treatment modality using nebulizing tranexamic acid to help manage epistaxis in patients that cannot be managed with topical antifibrinolytic therapy administered by other means.

Effect of Standardized Infliximab Dose Rounding on an Outpatient Infusion Center.

BACKGROUND: Infliximab dose rounding is a commonly accepted practice at many institutions to contain costs. Currently, there is limited data on the clinical and financial implications of infliximab dose rounding standardization. OBJECTIVE: To determine whether standardized infliximab dose rounding is comparable with nonstandardized dosing in patients with Crohn's disease or ulcerative colitis in terms of cost and efficiency, using a cost comparison between the 2 dosing methods at an outpatient infusion center attached to a community teaching hospital. METHODS: A retrospective electronic chart review was conducted to identify patients who received infliximab for ulcerative colitis or Crohn's disease over a 6-month period. The primary endpoint was cost comparison between the 2 dosing methods. The secondary outcomes were estimated time taken for order verification, number of order clarifications, increase in dose or frequency of infliximab, number of patients who switched to alternative therapy, and use of medications for adverse drug effects. Descriptive statistics and Fisher's exact test were used for data analysis. RESULTS: 72 patients met the inclusion criteria. Because of patient overlap during the study period, 45 patients (62.5%) were in the standardized rounding arm, and 69 patients (95.8%) were in the nonstandardized rounding arm. One patient in each arm required an increased dose or frequency of infusion (2.2% vs. 1.5%, P = 1.000). Standardized infliximab dose rounding had a theoretical cost savings of at least $104,640 per year (based on our rough annual census of 480 patients) compared with the nonstandardized method that had been used previously. The cost savings can also be translated as $218 per patient per month on average. The mean times to order verification were 10 vs. 12 minutes in the nonstandardized and standardized groups, respectively. Two patients in the nonstandardized group switched to alternative therapy. There was no difference in usage of rescue medications for adverse drug effects. CONCLUSIONS: Standardization of infliximab dose rounding resulted in increased efficiency in the pharmacy workflow by reducing time for order verification. Furthermore, standardized dose rounding resulted in a significant reduction in expenditure for infliximab for the institution. DISCLOSURES: No outside funding supported this research. The authors have nothing to disclose. This research was presented as a poster at the ASHP Midyear Clinical Meeting & Exhibition 2017; December 3-7, 2017; Orlando, FL.

Use of nitroglycerin ointment to treat primary and secondary Raynaud's phenomenon: a systematic literature review.

Raynaud's phenomenon (RP) is a microvascular condition in which reversible ischemic attacks occur in the extremities. Due to the unpredictable nature of these attacks, pharmacologic agents that can be administered on as-needed basis are currently being sought after. Topical nitrates are well suited for as-needed use, and several different formulations have been studied for the treatment of RP, including ointments, gels, patches, and tapes. However, these different dosage forms are not all equal in terms of safety and efficacy, and not every one is commercially available for use in clinical practice. Nitroglycerin ointment is commercially available, and it has less systemic side effects than other topical formulations. Since its role in the treatment of RP has not yet been completely established, we performed a systematic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials to evaluate its safety and efficacy. A total of 1125 studies were identified, and 7 were included in our review. Although the included studies used different measures of efficacy, the majority reported positive responses to nitroglycerin ointment. The benefit of nitroglycerin ointment in the treatment of RP may be further realized through more robust investigation.

Renal and Cardiac Implications of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors: The State of the Science.

OBJECTIVE: To review the role of the sodium-glucose cotransporter-2 (SGLT2) inhibitors in the management of type 2 diabetes (T2DM), including the effects on renal and cardiovascular (CV) outcomes. DATA SOURCES: A literature search of MEDLINE databases (1964 through May 2018) was conducted utilizing key words sodium-glucose co-transporter-2 inhibitors, SGLT2 inhibitors, and diabetes; additional limits for drug names were added. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of use of SGLT2 therapy specifically detailing outcomes on CV and renal disease in humans were reviewed. DATA SYNTHESIS: This review will explore the role of the SGLT2 inhibitors on CV and renal outcomes in patients with T2DM. Relevance to Patient Care and Clinical Practice: A paradigm shift regarding the regulation of medications for the treatment of T2DM has resulted in the need for CV outcomes data as part of the drug approval process. Reduction of major CV events and progression of nephropathy in patients with T2DM represent major outcomes of clinical significance. Few medications have been able to establish a reduction in these end points; data for the use of SGLT2 inhibitors are favorable in this regard. CONCLUSION: The SGLT2 inhibitors represents a class of medications that reduce glucose levels via a novel and complementary mechanism. Emerging evidence suggests a plausible explanation for the observed reduction in adverse renal and CV outcomes in recent clinical trials. Questions remain whether these agents reduce renal disease risk greater than achievement of the same glycemic goals as other antidiabetics and whether CV and renal benefits are reproducible in high-risk patients with chronic kidney disease.

Disaster Preparedness: Biological Threats and Treatment Options.

Biological disasters can be natural, accidental, or intentional. Biological threats have made a lasting impact on civilization. This review focuses on agents of clinical significance, bioterrorism, and national security, specifically Category A agents (anthrax, botulism, plague, tularemia, and smallpox), as well as briefly discusses other naturally emerging infections of public health significance, Ebola virus (also a Category A agent) and Zika virus. The role of pharmacists in disaster preparedness and disaster response is multifaceted and important. Their expertise includes clinical knowledge, which can aid in drug information consultation, patient-specific treatment decision making, and development of local treatment plans. To fulfill this role, pharmacists must have a comprehensive understanding of medical countermeasures for these significant biological threats across all health care settings. New and reemerging infectious disease threats will continue to challenge the world. Pharmacists will be at the forefront of preparedness and response, sharing knowledge and clinical expertise with responders, official decision makers, and the general public.

Therapeutic Interchange of Clevidipine For Sodium Nitroprusside in Cardiac Surgery.

BACKGROUND: Generic price inflation has resulted in rising acquisition costs for sodium nitroprusside (SNP), an agent historically described as the drug of choice for the treatment of perioperative hypertension in cardiac surgery. PURPOSE: To describe the implementation and cost avoidance achieved by utilizing clevidipine as an alternative to SNP in cardiac surgery patients at a 520-bed community teaching hospital that performs more than 300 cardiac surgeries each year. METHODS: A multidisciplinary team inclusive of anesthesiologists, intensivists, pharmacists, and surgeons collaborated to develop a therapeutic interchange for SNP in cardiac surgery patients. Consistent with current guidelines for therapeutic interchange, the goal was to encourage a less expensive alternative that was demonstrated to be at least therapeutically equivalent to SNP based on data derived from clinical trials published in peer-reviewed literature. A comprehensive literature review identified clevidipine as an alternative to SNP for perioperative hypertension in cardiac surgery. Nicardipine was considered as well, but was not chosen as a substitute due to lack of strong evidence and comparative data with SNP. RESULTS: Clevidipine was implemented successfully in our cardiac surgery patients and will result in a net cost avoidance of approximately $300,000 in 2016. This is thought to be driven largely by the difference in acquisition cost between clevidipine and SNP. The operating room in our institution no longer keeps SNP stocked in anesthesia trays as a result of the success of our interchange. No requests have been made to return to the SNP standard. CONCLUSION: Through effective communication and multidisciplinary collaboration, our institution was able to develop an evidence-based and effective therapeutic interchange program for SNP.

Evidence for the Use of Epoprostenol to Treat Raynaud's Phenomenon With or Without Digital Ulcers.

OBJECTIVE: To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud's phenomenon (RP). DATA SOURCES: The databases MEDLINE (1946 to March 2016), PubMed, and International Pharmaceutical Abstracts were searched using the terms epoprostenol, Flolan, Raynaud's disease, and CREST syndrome. Further literature sources were identified by reviewing article citations. STUDY SELECTION AND DATA EXTRACTION: All English-language, clinical trials and case series evaluating IV epoprostenol for the management or treatment of RP were included. Lower-quality evidence were incorporated due to limited information. DATA SYNTHESIS: Seven small uncontrolled studies/case series, 1 small placebo controlled study, and 1 larger randomized trial were identified and included. There was no consistent measurement of efficacy utilized, but improvements in hand temperature, RP attack duration and frequency were commonly associated with IV epoprostenol treatment (5 trials). There were conflicting data regarding effect sustainability, with 5 trials showing long-term effects and 3 showing immediate effects. Fewer ischemic ulcers developed during treatment with IV epoprostenol in 1 trial compared to conventional treatment. Ulcer healing ocurred in 2 trials. Common adverse effects included hypotension, headache, flushing, gastrointestinal symptoms, and jaw pain. CONCLUSIONS: Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.

Practice Guideline Development, Grading, and Assessment.

Published clinical practice guidelines (CPGs) are abundant and more easily accessible than ever because of advances in technology and communication and the widespread use of electronic medical literature. To make educated therapy recommendations based on published guidelines, it is important for clinicians to understand the process of guideline development and to be familiar with the resources used to assess guidelines. To do this, clinicians must know the commonly used systems for grading guideline recommendations and for evaluating guideline quality. By increasing their understanding of guideline development, grading, and evaluation processes, clinicians can appropriately use guidelines and provide the highest level of patient care.

Gluten content of medications.

PURPOSE: The establishment of a database for the identification of the presence of gluten in excipients of prescription medications is described. SUMMARY: While resources are available to ascertain the gluten content of a given medication, these resources are incomplete and often do not contain a source and date of contact. The drug information service (DIS) at Robert Wood Johnson University Hospital (RWJUH) determined that directly contacting the manufacturer of a product is the best method to determine the gluten content of medications. The DIS sought to establish a resource for use within the institution and create directions for obtaining this information from manufacturers to ensure uniformity of the data collected. To determine the gluten content of a medication, the DIS analyzed the manufacturer's package insert to identify any statement indicating that the product contained gluten or inactive ingredients from known sources of gluten. If there was any question about the source of an inactive ingredient or if no information about gluten content appeared in the package insert, the manufacturer of the particular formulation of the queried medication was contacted to provide clarification. Manufacturers' responses were collected, and medications were categorized as "gluten free," "contains gluten," or "possibly contains gluten." To date, the DIS at RWJUH has received queries about 84 medications and has cataloged their gluten content. CONCLUSION: The DIS at RWJUH developed a database that categorizes the gluten status of medications, allowing clinicians to easily identify drugs that are safe for patients with celiac disease.

The power of genes: a case of unusually severe systemic toxicity after localized hepatic chemoembolization with irinotecan-eluted microspheres for metastatic colon cancer.

OBJECTIVE: To report a case of systemic irinotecan toxicity following regional transarterial chemoembolization with drug-eluting beads loaded with irinotecan (DEBIRI-TACE) in a patient later found to have a homozygous mutation for UGT1A1*28. CASE SUMMARY: An 80-year-old woman presented with a cecal colon cancer with synchronous metastases to the liver. After resection of the primary tumor, the patient underwent DEBIRI-TACE with 100 mg of irinotecan to treat the residual disease in the liver. A week after this procedure, the patient developed grade 4 neutropenia, and later, alopecia. Eventually, it was found that the patient had a mutation of UDP glucuronosyltransferase 1 family polypeptide A1 (UGT1A1), which provided a reasonable explanation for the observed reaction. DISCUSSION: The toxic effects of irinotecan are well understood. Patients with genetic polymorphisms of the genes encoding for the enzyme UGT1A1 may have increased incidence of irinotecan-associated toxicities because of decreased clearance of the active metabolite SN38 via the glucuronidation pathway. To date, there have been limited publications describing systemic adverse events following TACE or DEBIRI-TACE and, based on a thorough literature search, none following these procedures in patients with UGT1A1 polymorphisms. Based on the scoring results of the Naranjo algorithm (7), we are confident in attributing the observed reaction to the patient's genetic polymorphism. CONCLUSION: Although genetic testing prior to the initiation of irinotecan therapy is not currently recommended, assessment of UGT1A1 polymorphism is warranted when severe adverse events typical of systemic therapy manifest following DEBIRI-TACE.