Scott W. Savage

Vemurafenib (PLX4032): An Orally Available Inhibitor of Mutated BRAF for the Treatment of Metastatic Melanoma

Objective: To summarize the preclinical and clinical data on vemurafenib, approved by the Food and Drug Administration (FDA) on August 17, 2011, and discuss the drugs clinical advantages and limitations. Data Sources: An English-language literature search of MEDLINE/PubMed (1966-August 2011), using the terms PLX4032, RG7204, R05185426, vemurafenib, and metastatic melanoma, was conducted. In addition, information and data were obtained from meeting abstracts, clinical trial registries, and news releases from the FDA. Study Selection and Data Extraction: All relevant published articles and abstracts on vemurafenib were included. Clinical trial registries and meeting abstracts were used to obtain information regarding ongoing trials. All peer-reviewed articles containing information regarding the clinical safety and efficacy of vemurafenib were evaluated for inclusion. Data Synthesis: Before the recent approval (March 2011) of ipilimumab, there was no first-line standard-of-care therapy, with proven overall survival benefit, for the treatment of malignant metastatic melanoma. Unlike ipilimumab, which acts through immune-modulation, vemurafenib is a novel, molecularly targeted therapeutic with preferential efficacy toward a specific mutated oncogenic BRAF-signaling mediator. In recently published results of a Phase 3 clinical trial comparing dacarbazine with vemurafenib, vemurafenib prolonged progression-free and overall survival, with confirmed objective response rate of 48% (95% CI 42 to 55) versus 5% (95% CI 3 to 9) for patients who received dacarbazine (p < 0,001) Conclusions: Vemurafenib offers a novel, first-line, personalized therapy for patients who have mutated BRAF, Clinical trials of vemurafenib in combination with ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with long-term clinical benefit.

Integration of a clinical pharmacist into the hematology–oncology clinics at an academic medical center

PURPOSE The development, implementation, and early experience with a program providing clinical pharmacist services at the hematology-oncology clinics of a university teaching hospital are described. SUMMARY With funding from a university research grant and other sources, a pharmacist was hired to launch a new program addressing four goals identified in a needs assessment: (1) improved management of supportive care, (2) enhanced education of patients receiving complicated chemotherapy regimens, (3) improved efficiency in the chemotherapy infusion unit, and (4) development of an experiential learning opportunity for pharmacy students and residents. The pharmacist hired to lead the ongoing program was a state-approved clinical pharmacist practitioner (CPP) who had authority to prescribe with physician oversight under established protocols. EXPERIENCE An oncology supportive care consultation service implemented by the CPP in collaboration with a nurse and a physician served 89 new patients in its first 18 months of operation; during that period the CPP made 186 interventions and wrote 136 prescriptions. The CPP also established a chemotherapy counseling service that provided more than 900 bill-able patient education sessions over 18 months. In addition, the CPP launched an effort to increase use of a rituximab rapid-infusion protocol among eligible patients. The creation of the new oncology pharmacist position has given dozens of pharmacy students and residents a new opportunity for interaction with oncology clinic patients and other health care team members. CONCLUSION Integration of the services of a CPP into the hematology-oncology clinics has helped achieve goals set by physician, nursing, and pharmacy leaders.

The Role of Mannitol as a Nephroprotectant in Patients Receiving Cisplatin Therapy

Objective: To review the efficacy and safety of concomitant mannitol administration with cisplatin therapy to reduce the incidence of nephrotoxicity. Data Sources: A literature search was performed via MEDLINE, PubMed, and the Cochrane Library (1945-August 2011) using the terms mannitol, cisplatin, nephrotoxicity, and forced diuresis. Reference citations from the publications identified were also reviewed. Study Selection and Data Extraction: The search was limited to studies conducted in humans. All studies in which mannitol was used for forced diuresis with cisplatin therapy were evaluated. Data Synthesis: Cisplatin therapy can lead to transient and permanent renal impairment. Molecular and histologic changes occur in the renal tubules, which contribute to nephrotoxicity. The adverse effect profile of cisplatin is well documented, but the prevention strategies to alleviate renal impairment due to treatment are less understood. Mannitol plus hydration has been used for several years to alleviate toxicity associated with cisplatin therapy. However, the data for mannitol administration have not been convincing. When the use of mannitol and hydration is compared directly to hydration alone, mannitol shows no benefit. In some patients, not only was mannitol not protective, its administration was associated with worsening renal function. Conclusions: Although mannitol plus hydration is used to decrease cisplatin-induced nephrotoxicity, there are no compelling data that the addition of mannitol is more nephroprotective than the use of hydration alone. Appropriate hydration remains the most reasonable strategy to reduce the incidence of cisplatin-induced nephrotoxicity.

Economic and Microbiologic Evaluation of Single-Dose Vial Extension for Hazardous Drugs

PURPOSE The update of US Pharmacopeia Chapter <797> in 2008 included guidelines stating that single-dose vials (SDVs) opened and maintained in an International Organization for Standardization Class 5 environment can be used for up to 6 hours after initial puncture. A study was conducted to evaluate the cost of discarding vials after 6 hours and to further test sterility of vials beyond this time point, subsequently defined as the beyond-use date (BUD). METHODS Financial determination of SDV waste included 2 months of retrospective review of all doses prescribed. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trypticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD. RESULTS The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at

Assessment of final product dosing accuracy when using volumetric technique in the preparation of chemotherapy

766,000 annually, and tracking waste logs for these same medications was recorded at

Precision Dosing: Public Health Need, Proposed Framework, and Anticipated Impact

770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process. CONCLUSION The cost of discarding vials at 6 hours was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represented exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than

Improving employee engagement within a department of pharmacy

600,000.

Pharmacy-Initiated Transitions of Care Services: An Opportunity to Impact Patient Satisfaction.

Background Studies have compared gravimetric and volumetric dosing accuracies in chemotherapy agents, finding high accuracy in gravimetric measurements with a mean deviation of ± 0.06%, while volumetric measurements had a mean deviation of ± 3.02%. Methods Chemotherapy doses prepared under a biological safety cabinet containing two weights from the precision scale between 15 December 2010 and 30 March 2011 were eligible for inclusion. Empty syringes attached to a closed-system transfer device were weighed prior to product manipulation. The product was then prepared using the syringe pull-back method (volumetric technique) and the same syringe containing drug was weighed (gravimetric method). Results A total of 1156 compounded sterile products were eligible for the study. The mean percent volume difference of preparations included was –0.53% with a range of –64.9% to 94.22% for individual doses. Of the prepared doses, 71.7% were within ± 5% and 87.4% were within ± 10% of the ordered dose. Secondary outcomes found to be associated with an increased percent volume difference were the pediatric population, smaller volumes prepared, drugs requiring reconstitution compared to already in solution, and final product dispensed to the patient in syringes. Conclusion While the mean value of volumetric measurements is within the generally understood acceptable range for dispensing chemotherapy, the range of measurements is highly variable. Future studies are warranted to better understand the reasons behind the variation and to evaluate the impact of workflow changes on improving final product accuracy.

Improved Adherence Rates and Clinical Outcomes of an Integrated, Closed-Loop, Pharmacist-Led Oral Chemotherapy Management Program

“Precision dosing” focuses on the individualization of drug treatment regimens based on patient factors known to alter drug disposition and/or response. In 2015, over 8 in 10 nonfederal acute care hospitals in the United States had adopted a basic electronic health record (EHR) system,1 which will facilitate the application of precision dosing. Expanding on recent publications,2, 3 we outline the public health need, a proposed framework, and the anticipated impact for the adoption of precision dosing.

Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing

Employee engagement is a method used in the workplace to ensure that employees are committed to their organization’s mission, vision, and goals.[1][1]–[4][2] Positive engagement improves employee performance and efficiency, which contribute to an organization’s overall success.[5][3] Engaged