Colchicine in Acute Coronary Syndrome: A Systematic Review.

OBJECTIVE: The purpose of this review is to evaluate the efficacy and safety of colchicine after acute coronary syndrome (ACS). DATA SOURCES: English-language searches were made of MEDLINE and EMBASE from database inception through mid-June 2020. STUDY SELECTION AND DATA EXTRACTION: Randomized trials characterizing the effects of colchicine in ACS were considered. Of 627 title and abstracts identified, nine trials were included. Two reviewers extracted data and rated study quality. DATA SYNTHESIS: Four studies showed colchicine did not attenuate C-reactive protein production. Colchicine did modulate the NOD-like receptor family pyrin domain containing 3 inflammasome in 3 studies and reduced production of chemokine ligand 2 (CCL2), CCL5, and C-X3-C motif chemokine ligand 1 in 1 study. Major adverse cardiovascular events (MACE) were not significantly different at 30 days in 3 studies, administered as 1.8 mg preprocedurally or scheduled 1 mg daily. One study found a significant reduction in MACE with colchicine 0.5 mg daily over median 22.6 months (hazard ratio = 0.77; 95% CI = 0.61-0.96). Colchicine is associated with increased gastrointestinal adverse events but was generally well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Colchicine is likely to reduce MACE in an ACS population if administered for greater than 30 days but does not improve MACE when administered only preprocedurally. CONCLUSIONS: Adjunctive colchicine 0.5 mg daily for greater than 30 days is reasonable for an ACS population on guideline-directed medical therapy treated with PCI. Additional studies are needed to validate and determine the durability of these benefits.

Safety analysis of long-term phenazopyridine use for radiation cystitis.

BACKGROUND: Phenazopyridine is a urinary tract analgesic indicated for short-term treatment of irritation in the lower urinary tract. Despite the lack of evidence for extended use, it is often used in varying durations for supportive care for cancer patients with radiation-induced cystitis. The objective of this study was to compare the incidence of adverse drug reactions in patients with radiation cystitis receiving long-term phenazopyridine (>14-day supply) compared to a matched comparator group. METHODS: This retrospective cohort study compared adverse events among cancer patients with and without phenazopyridine exposure. Included patients received radiation and at least one chronic medication between 1 July 2008 and 30 June 2017. The phenazopyridine group also received >14-day supply of phenazopyridine during the study period. Patients were matched based on gender, age (±5 years), cancer diagnosis, and palliative or curative treatment intent. Data collection occurred at baseline, during the time of presumed exposure, and through the end of the study period for surveillance purposes. RESULTS: A total of 272 patients received phenazopyridine for >14-day supply during the study period. Of these, 90 patients were included and matched to an equal number of patients in the comparator group. The included patients were similar between groups and were largely male with a diagnosis of prostate cancer. Most patients received between a 30- and 60-day supply of phenazopyridine. There were a total of 13 adverse drug reactions in the phenazopyridine group and 18 in the comparator group (p = 0.32). No differences were identified between the phenazopyridine and comparator groups for the incidence of individual adverse drug reactions, emergency department visits, hospitalizations, or new diagnoses of hepatocellular or colorectal cancer. CONCLUSION: There was no difference in adverse drug reactions among patients receiving phenazopyridine for >14 days compared to a matched comparator group. The overall incidence of adverse events in both groups was low.

Medication Safety in Clinical Trials: Role of the Pharmacist in Optimizing Practice, Collaboration, and Education to Reduce Errors.

Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards. Ultimately, the profession of pharmacy has foundational responsibility for assuring the safe and effective use of medications, including investigational drugs in clinical research. It is through multidisciplinary collaboration that a research study will attain the highest standards for safety and maximize the quality and effectiveness of the data obtained in the clinical trial.

Comparison of the Effectiveness of Liraglutide vs Semaglutide in a Veteran Population.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed medications for patients with type 2 diabetes mellitus (T2DM) based on cardiovascular benefits. Objective: This study aimed to evaluate efficacy and tolerability of once daily liraglutide vs once weekly semaglutide on T2DM in a Veteran population. Methods: This was a retrospective, single-center, cohort study that included T2DM patients with a prescription for liraglutide or semaglutide between September 1st, 2019, and September 30th, 2020. Patients between groups were matched based on age and insulin use at baseline. The primary endpoint was the difference in hemoglobin A1c (A1c) between the most recent A1c in the study period and baseline A1c obtained prior to GLP-1 RA initiation. Results: There were 154 patients included in the study. While mean reduction in A1c was numerically higher in the liraglutide group (-1.1% vs. -.8%), this was not statistically significant (P = .22). The proportion of patients achieving A1c < 7%, < 8%, < 9%, or their patient-specific A1c goal did not differ between groups. Although baseline total daily doses of insulin were higher in the semaglutide group, these patients had numerically greater reductions in total daily dose of insulin and weight from baseline; however, no statistical difference was observed. Adverse drug reactions were more common in the semaglutide group (n = 14 vs. 9), leading to higher discontinuation rates as well (n = 11 vs. 8). Conclusion: The results of this study indicate no difference between liraglutide and semaglutide in terms of A1c-lowering potential, but it provides insights into key considerations for the Veteran population.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

Impact of national valsartan recalls on Veterans' outcomes.

BACKGROUND AND AIMS: Chemical impurities discovered in angiotensin receptor blocker (ARB) products in late 2018-2019 resulted in recalls of various products and has likely had downstream effects for patients and prescribers. The purpose of this study is to determine how the valsartan recall impacted clinical endpoints and prescribing of antihypertensives. METHODS: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with essential hypertension who were mailed a recall letter on 12 March 2019. Mean blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Antihypertensive medication changes and titrations were also characterized post-recall. RESULTS: A total of 300 patients meeting eligibility criteria were included. There was no statistically significant difference in mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg, p = 0.125; DBP: 78.6 mmHg versus 78.5 mmHg, p = 0.900). In addition, the percentage of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%, p = 0.72). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB (n = 11) or drug class (n = 12). In total, 11 valsartan medication changes were specifically documented to be related to the valsartan recall. CONCLUSION: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population. PLAIN LANGUAGE SUMMARY: Impact of a medication recall on Veterans' outcomesBackground:: Chemical impurities discovered in a class of blood pressure medications known as angiotensin receptor blockers (ARBs) occurred in late 2018-2019. This resulted in recalls of various products and has likely had downstream effects for patients and prescribers.Objective:: The purpose of this study is to determine how the recall of valsartan, which is a medication in the ARB class, impacted clinical endpoints and prescribing of medications for blood pressure.Methods:: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with high blood pressure who were mailed a recall letter on 12 March 2019. Blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Medication changes and titrations were also characterized post-recall.Results:: Three hundred patients meeting eligibility criteria were included. There was no difference found in systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg; DBP: 78.6 mmHg versus 78.5 mmHg). In addition, the percent of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB (n = 11) or drug class (n = 12). Eleven valsartan medication changes were specifically documented to be related to the valsartan recall.Conclusions:: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population.

Assessing the Economic Value of Pharmacy Resident Participation in an Investigational Drug Service.

PURPOSE: Completion of postgraduate residency training gives pharmacists an opportunity to gain advanced practice experience, yet the availability of these positions is often limited. Through participation in an investigational drug service (IDS), residency programs may be able to expand learning experiences while demonstrating a financial benefit to the institution. The purpose of this assessment is to examine the economic value generated by pharmacy resident involvement within an IDS. METHODS: This was a single-center retrospective record review. All resident dispensations within the IDS from January 1, 2016, to December 31, 2017, were evaluated for cost avoidance, revenue, and waived revenue. Cost avoidance was defined as the cost of medications the institution would have incurred had the sponsor not provided therapies free of charge. Medical center contract acquisition costs were used to determine cost avoidance. Total economic value accounted for the personnel costs of resident dispensations. Descriptive statistics were utilized for all assessments. RESULTS: A total of 444 resident dispensations occurred during the study period on 15 IDS protocols. The total cost avoidance for resident dispensations was US$144 898. Total revenue for these dispensations was US$1424, and waived revenue fees totaled US$17 625. After accounting for the personnel cost of dispensations by the residents, the total economic value of resident participation in the IDS was US$159 150. CONCLUSION: Resident participation in the IDS contributed economic value to the institution. The IDS provides a unique learning experience for the pharmacy residents, cost savings for the institution, and supports the advancement of patient care.

Economic outcomes associated with an investigational drug service within a Veterans Affairs health care system.

BACKGROUND: An investigational drug service (IDS) has a foundational role in ensuring the safe and efficient management of investigational drugs. The objective of this assessment is to determine economic value of an IDS within a Veterans Affairs health care system. METHODS: This assessment was a single-center retrospective record review. Study protocols managed by the IDS over a 2-year period were evaluated for cost avoidance, revenue, and waived revenue. Cost avoidance was defined as the cost savings generated when a research subject received sponsor-provided treatment in place of a therapy that would have been otherwise funded by the institution. Revenue from fees charged to investigators and waived revenue based on the standardized IDS fee schedule were also totaled. The total economic value to the institution accounted for the personnel costs of the IDS. RESULTS: Twenty-three investigational study protocols managed by the IDS resulted in economic outcomes. The total cost avoidance during the two-year period was $482,627.33. The total revenue and waived revenue associated with the IDS was $16,822 and $54,200, respectively. Oncology protocols had the highest contribution to the outcomes of cost avoidance and revenue and mental health protocols had the highest contribution for waived revenue. The overall economic value of the IDS to the institution was $393,649.33. CONCLUSIONS: Over a two-year period, the IDS demonstrated a substantial economic value that was largely driven by cost avoidance. Revenue generation from fees charged to investigators and cost savings to the investigator through waived revenue also contributed economic benefits to the institution.

The Role of Xanthine Oxidase Inhibitors in Patients with History of Stroke: A Systematic Review.

BACKGROUND: Xanthine oxidase inhibitors are commonly used to lower uric acid levels in patients with gout. Due to their effects on endothelial function, they have also been investigated for possible benefits for patients with cardiovascular disease. OBJECTIVE: To assess the efficacy and safety of xanthine oxidase inhibitors in the treatment of patients with history of stroke. METHODS: MEDLINE (1946-June 2017) and EMBASE (1947-June 2017) were queried using the search terms: "allopurinol" OR "febuxostat" OR "xanthine oxidase inhibitor" OR "xanthine oxidase/ antagonists and inhibitors" AND "stroke" OR "cerebral infarction" OR "cerebrovascular accident". Studies appropriate to the objective were evaluated, including five randomized, placebo-controlled, double-blind trials investigating the effect of allopurinol in patients with history of stroke. No articles evaluating the use of febuxostat in this setting were identified. RESULTS: In patients with history of stroke, treatment with allopurinol resulted in improvements in several markers of endothelial function, inflammatory markers, and scores on the Modified Rankin Scale. Study durations ranged from 6 weeks to 1 year, and studies used varying doses of allopurinol. Allopurinol was well tolerated in most studies, with some reports of gastrointestinal adverse effects, headache and rash. CONCLUSION: Based on the reviewed literature, allopurinol appears to be a promising therapy to improve vascular function and reduce disability in patients who have had a stroke. The benefits seen are in combination with current standard of care treatments with aspirin and lipid-lowering therapy. Larger trials are necessary to better understand the role of allopurinol in patients with history of stroke.

Pharmacy resident involvement in prior-authorization drug request adjudication.

PURPOSE: Results of a study to determine economic outcomes of pharmacy residents' involvement in prior-authorization drug request (PADR) adjudication within a Veterans Affairs (VA) healthcare system are reported. METHODS: A retrospective review was conducted to identify PADRs adjudicated by pharmacy residents under a preceptor's supervision during the 2015-16 residency year. Only PADRs that were not approved as submitted (i.e., only those requiring formulary intervention) and that met other inclusion criteria were included in the analysis. Prior-authorization requests and adjudication decisions were characterized, and cost savings resulting from those decisions were calculated. RESULTS: Of the total of 752 PADRs adjudicated by 6 pharmacy residents during the study period, 42 met the inclusion criteria. About 90% of included PADRs were categorized as general medicine requests, and 9.5% were for oncology medications. The most common rationale for PADR nonapproval (cited in 60% of requests) was the availability of a preferred formulary alternative; the remainder of nonapprovals were due to medication safety concerns (e.g., contraindication to therapy, drug interaction potential, likelihood of adverse drug event resulting in patient harm, history of allergy to requested medication). Resident adjudication of PADRs resulted in total direct cost savings of $169,877.53 over the 12-month period, a mean of $4,044.70 per request. CONCLUSION: Pharmacy residents' involvement in adjudicating PADRs at a VA healthcare system resulted in substantial cost savings over the course of the residency year.

Aripiprazole for Post-traumatic Stress Disorder: A Systematic Review.

OBJECTIVE: The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). METHODS: A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review. RESULTS: In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence. CONCLUSIONS: Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.

Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans.

STUDY OBJECTIVE: To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. DESIGN: Case series. SETTING: Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System. PATIENTS: Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. MEASUREMENTS AND MAIN RESULTS: All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. CONCLUSION: To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.