Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review.

OBJECTIVE: To review the pharmacokinetic (PK)-pharmacodynamic (PD) profiles, disease setting, dosing, and safety of oral and parenteral hypomethylating agents (HMAs) for the treatment of myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML), and to provide a multidisciplinary perspective on treatment selection and educational needs relating to HMA use. DATA SOURCES: Clinical and real-world data for parenteral decitabine and azacitidine and two oral HMAs: decitabine-cedazuridine (DEC-C) for MDS and azacitidine (CC-486) for AML maintenance therapy. DATA SUMMARY: Differences in the PK-PD profiles of oral and parenteral HMA formulations have implications for their potential toxicities and planned use. Oral DEC-C (decitabine 35 mg and cedazuridine 100 mg) has demonstrated equivalent systemic area under the concentration-time curve (AUC) exposure to a 5-day regimen of intravenous (IV) decitabine 20 mg/m2 and showed no significant difference in PD. The AUC equivalence of oral DEC-C and IV decitabine means that these regimens can be treated interchangeably (but must not be substituted within a cycle). Oral azacitidine has a distinct PK-PD profile versus IV or subcutaneous azacitidine, and the formulations are not bioequivalent or interchangeable owing to differences in plasma time-course kinetics and exposures. Clinical trials are ongoing to evaluate oral HMA combinations and novel oral HMAs, such as NTX-301 and ASTX030. CONCLUSIONS: Treatment with oral HMAs has the potential to improve quality of life, treatment adherence, and disease outcomes versus parenteral HMAs. Better education of multidisciplinary teams on the factors affecting HMA treatment selection may help to improve treatment outcomes in patients with MDS or AML.

Managing Conflict: A Guide for the Pharmacy Manager.

Managing conflict among a variety of people and groups is a necessary part of creating a high performance pharmacy department. As new pharmacy managers enter the workforce, much of their success depends on how they manage conflict. The goal of this article is to provide a guide for the pharmacy director on conflict in the workplace. By evaluating each type of conflict, we can learn how to respond when it occurs. Resolving conflict requires a unique and individualized approach, and the strategy used may often be based on the situational context and the personality of the employee or manager. The more that pharmacy leaders can engage in conflict resolution with employees and external leaders, the more proactive they can be in achieving positive results. If pharmacy directors understand the source of conflicts and use management strategies to resolve them, they will ensure that conflicts result in a more effective patient-centered pharmacy service.

Life in a fishbowl: accountability and integrity in pharmacy leadership.

The Director's Forum is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems by providing practical information on various leadership topics. Pharmacists are bound to practice in the best interest of the patient and are obligated to act with integrity and in an ethical manner. Pharmacy directors and their leadership staff are additionally bound to manage their department with integrity. Staff often scrutinize the pharmacy director's actions, giving the director a feeling of "life in a fishbowl." Every action of the leader is judged in the context of personal integrity or their individual commitment to moral, spiritual, and ethical values. The objective of this article is to describe how a pharmacy leader manages this responsibility. This article addresses the pharmacy leader's obligations to act with integrity, reviews key integrity concerns in pharmacy leadership, and provides guidance for leading and managing in the context of ethics and integrity. Pharmacy directors must always be aware that they are open to both department and public scrutiny if they do not conduct themselves in a professional manner. Being accountable for their actions and maintaining a high standard of integrity, leaders can keep the focus of their departments on the goal of patient-centered pharmacy services.

Optimizing the management of inherited blood disorders in a changing market: Findings from the AMCP Market Insights Program.

In this market insights program, AMCP brought together a panel of experts representing various stakeholders: national and regional health plans, integrated health care systems, employer benefits groups, clinical experts, the Centers for Disease Control and Prevention, and patient advocacy organizations. The objectives were to gain insights into the current and evolving treatments in hemophilia, sickle cell disease, and ß-thalassemia; measure the effects of recently approved therapies on clinicians, payers, and patients; recognize emerging trends within the stop-loss market; address potential issues and obstacles related to monitoring and reporting outcomes; and identify concerns associated with both existing and emerging contracting and reimbursement models. This article aims to summarize expert perspectives on health care system challenges and strategies concerning the management of inherited blood disorders and to advance managed care professionals' understanding of their role in supporting care for these patients. The experts emphasized that when shaping coverage policies, a patient-centered approach is crucial, focusing on preserving organ function to maintain eligibility for future gene therapies among individuals with inherited blood disorders. These strategies, including benefit design modifications, specialized provider networks, and centralized mechanisms like registries, are vital for evaluating effectiveness, facilitating decision-making, and managing costs and risks associated with new and emerging treatment options for inherited blood disorders.

Payer and provider solutions to utilization management challenges in the management of rare hematologic cancers.

Patients with rare diseases such as Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), a hematologic malignancy affecting approximately 1500 new patients per year, experience barriers to care involving both clinical and administrative factors. Optimal patient outcomes depend on timely identification, diagnosis of disease, and treatment initiation. For patients living with Ph+ ALL, the process can be delayed by limited treatment options approved by the US Food and Drug Administration and administrative hurdles that often delay treatment initiation. An overhaul of utilization management processes, such as the requirement for prior authorization (PA) for treatment, are needed to ensure patients have access to appropriate treatments in a timely manner. An AJMC Roundtable in November 2022 brought together a panel of payers and providers to discuss the challenges and shortcomings of current PA processes and to present ideas for potential solutions for improving them. Panelists at the roundtable discussed approaches including the use of guideline-concordant electronic PAs and other digital solutions, expedited approval pathways for use in specific conditions, use of real-world evidence in decision-making, issuance of PA "Gold Cards" to select providers, and a shift to value-based care agreements. Roundtable attendees agreed that, regardless of the strategy for PA-process improvement, there is a need for improved communication between providers and payers to ensure that the decision-making system meets the essential need for timely patient access to optimal care. This article reviews utilization management and guideline-concordant care through the lens of rare diseases and then presents solutions to utilization.

The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review.

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.

Comparison of rates of adherence to oral chemotherapy medications filled through an internal health-system specialty pharmacy vs external specialty pharmacies.

PURPOSE: The primary objective of the study described here was to compare rates of patient adherence to anticancer medications filled at an internal health system specialty pharmacy (HSSP) vs external specialty pharmacies. The primary outcome was the medication possession ratio (MPR), and the secondary outcomes included proportion of days covered (PDC), and time to treatment (TTT). METHODS: A retrospective chart review was conducted to compare the MPR, PDC, and TTT for patients who received oral anticancer therapy using prescriptions claim data. A t test or Wilcoxon test was used to explore the effect of demographic and other factors on adherence and TTT. A multiple regression model with backward elimination was used to analyze significant factors to identify covariates significantly associated with the outcomes. RESULTS: Of the 300 patients screened for study inclusion, 204 patients whose records had complete MPR and PDC data and 164 whose records had TTT data were included in the analysis. There were significant between-group differences in mean MPR and mean PDC with patient use of the HSSP vs external pharmacies (1.00 vs 0.75 [P < 0.001] and 0.95 vs 0.7 [P < 0.001], respectively). Pharmacy type (P = 0.024) and tumor type (P = 0.048) were significantly associated with TTT. CONCLUSION: The multiple regression analysis indicated that oncology patients who filled their anticancer medication precriptions at an internal HSSP at an academic medical center had significantly higher adherence, as measured by MPR and PDC, and quicker TTT than those who filled their prescriptions at an external specialty pharmacy.

Postmenopausal females and the link between oral bisphosphonates and osteonecrosis of the jaw: a clinical review.

PURPOSE: To increase awareness for nurse practitioners (NPs) of new information concerning the plausible link between the oral bisphosphonate drug classification and necrosis in the jaw. DATA SOURCES: Selected research and clinical articles. In addition, several peer-reviewed, refereed medical and dental journals were consulted. CONCLUSIONS: Oral bisphosphonates are commonly prescribed by NPs for postmenopausal females with the diagnosis of osteoporosis to arrest bone loss and preserve bone density. Recent reports have shown a link between these medications and osteonecrosis of the jaw, which is a complication resulting in necrotic bone inside the mouth. IMPLICATIONS FOR PRACTICE: NPs must be able to determine early warning signs of osteonecrosis to ensure prompt referral to a dental specialist in order to prevent irreversible sequelae. Because of the aging population, osteoporosis is predicted to increase; therefore, treatment with these drugs and the side effects that go along with them will most likely also increase.

The importance of oral health in long-term care.

Emerging evidence has shown a strong link between the effects of chronic oral inflammation and general health. The mouth is the visible gateway to the rest of the body and reflects what is happening deep inside. Periodontal disease has been linked to systemic disease; likewise, systemic disease can have an impact on oral health. In fact, there are over 100 systemic diseases that have oral manifestations, such as cardiovascular disease, stroke, respiratory infections, pancreatic cancer, diabetes, and nutritional problems. This is a bidirectional relationship and the link is inflammation. Oral health problems can have an adverse effect on the quality of life and are more prevalent in older adults, but are not caused by aging. Approximately 75% of baby boomers will enter long-term care facilities with the majority of their natural teeth and this trend is expected to continue. Studies indicate that residents with good oral care require less health care dollar expenditures. Therefore, dental professionals, such as the dental hygienist, should be part of the multidisciplinary team to assist in providing expert regular dental care and training to caregivers and other health care professionals in long-term care facilities.