Outcome of preoperative cefazolin use for infection prophylaxis in patients with self-reported penicillin allergy.

BACKGROUND: Cephalosporins are the preferred antibiotics for prophylaxis against surgical site infections. Most studies give a rate of combined IgE and non-IgE penicillin allergy yet it is recommended that cephalosporins be avoided in patients having the former but can be used in those with the latter. Some studies use penicillin allergy while others penicillin family allergy rates. The primary goal of this study was to determine the rates of IgE and non-IgE allergy as well as cross reactions to both penicillin and the penicillin family. Secondary goals were to determine the surgical services giving preoperative cefazolin and the types of self reported reactions that patients' had to penicillin prompting their allergy status. METHODS: All patients undergoing elective and emergency surgery at a University Health Sciences Centre were retrospectively studied. The hospital electronic medical record was used for data collection. RESULTS: 8.9% of our patients reported non-IgE reactions to penicillin with a cross reactivity rate of 0.9% with cefazolin. 4.0% of our patients reported IgE reactions to penicillin with a cross reactivity rate of 4.0% with cefazolin. 10.5% of our patients reported non-IgE reactions to the penicillin family with a cross reactivity rate of 0.8% with cefazolin. 4.3% of our patients reported IgE reactions to the penicillin family with a cross reactivity rate of 4.0% with cefazolin. CONCLUSIONS: Our rate of combined IgE and non-IgE reactions for both penicillin and penicillin family allergy was within the range reported in the literature. Our rate of cross reactivity between cefazolin and combined IgE and non-IgE allergy both to penicillin and the penicillin family were lower than reported in the old literature but within the range of the newer literature. We found a lower rate of allergic reaction to a cephalosporin than reported in the literature. We documented a wide range of IgE and non-IgE reactions. We also demonstrated that cefazolin is frequently the preferred antibiotics for prophylaxis against surgical site infections by many surgical services and that de-labelling patients with penicillin allergy is unnecessary.

ONS Guidelines™ for Cancer Treatment-Related Hot Flashes in Women With Breast Cancer and Men With Prostate Cancer.

PURPOSE: Hot flashes are a common and troublesome side effect of surgery or endocrine therapy. They may lead to physical and psychological distress and negatively affect quality of life. This clinical practice guideline presents evidence-based recommendations for pharmacologic, behavioral, and natural health product interventions for treatment-related hot flashes in patients with breast or prostate cancer. METHODOLOGIC APPROACH: An interprofessional panel of healthcare professionals with patient representation prioritized clinical questions and patient outcomes for the management of hot flashes. Systematic reviews of the literature were conducted. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess the evidence and make recommendations. FINDINGS: The panel agreed on 14 pharmacologic, behavioral, and natural health recommendations. IMPLICATIONS FOR NURSING: Conditional recommendations include the use of antidepressants rather than no treatment, physical activity rather than no treatment, and the avoidance of gabapentin and dietary supplements in the treatment of hot flashes. SUPPLEMENTARY MATERIAL CAN BE FOUND AT HTTPS: //onf.ons.org/ons-guidelines-hot-flashes-supplementary-material.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

Women in oncology pharmacy leadership: A white paper.

Gender disparity exists in leadership roles within healthcare. While the majority of the healthcare workforce is comprised of women, significantly fewer women occupy leadership positions, particularly at executive and board levels. As the field of oncology pharmacy continues to rapidly expand and evolve, an assessment of the current state of women in oncology pharmacy leadership roles is vital to the growth and development of the profession. In the fall of 2017, the Hematology/Oncology Pharmacy Association (HOPA) hosted a summit to explore leadership issues facing women in oncology pharmacy which have the potential to affect our membership and our profession. This meeting included invited participants from across the fields of oncology and pharmacy and was part of HOPA's strategic leadership initiative developed through the work of the HOPA Leadership Development Committee in 2016. This promotes a primary goal of HOPA, which is to support oncology pharmacists as they assume leadership roles within their practices and within healthcare to assure oncology pharmacy is integrated into cancer care. The purpose of this white paper is to (1) summarize key issues that were identified through a membership survey; (2) review ongoing efforts to address the needs of female oncology pharmacists in leadership development; (3) serve as a call to action for individuals and professional organizations to assist with and disseminate these efforts and highlight available resources, and (4) to provide practical steps to meet the needs of individuals, training programs, and institutions/employers.

NCCN Guidelines Insights: Antiemesis, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.

Incidence, risk factors, and management of infusion-related reactions in breast cancer patients receiving trastuzumab.

BACKGROUND: Trastuzumab has become a mainstay of therapy for human epidermal growth factor receptor-2 overexpressed breast cancer in nearly all stages of the disease. Like many monoclonal antibodies, trastuzumab is associated with infusion-related reactions (IRRs) that are not well described, and incidence varies widely between reports (0.7%-40% of patients). MATERIALS AND METHODS: A retrospective chart review of breast cancer patients who received trastuzumab was conducted. The primary objective was to describe the incidence, risk factors, and management of IRRs during the first 12 weeks of trastuzumab therapy in a general population of breast cancer patients. RESULTS: A total of 197 patients who received trastuzumab (1,788 doses) were evaluated. Thirty-three IRRs were identified in 32 patients, resulting in an incidence of 16.2% of patients and 1.8% of doses. All IRRs were mild or moderate in severity and were successfully managed with supportive medications and/or by temporarily stopping the infusion. All patients received subsequent cycles of trastuzumab, with only one patient experiencing a subsequent reaction. Body mass index, stage of disease, and use of premedications were significantly associated with IRRs by multivariate logistic regression analysis. CONCLUSION: Overall, these results support that the vast majority of IRRs occur with the first infusion, are mild in severity, and are easily managed. In addition, risk factors were identified that may help to identify a population of patients at increased risk of IRRs who may benefit from premedication.

Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases.

BACKGROUND: Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. METHODS: Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. RESULTS: Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. CONCLUSIONS: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.

Evaluation of pharmacist-provided medication therapy management services in an oncology ambulatory setting.

OBJECTIVES: To determine the effect of formal medication therapy management (MTM) services on pharmacist workload, as well as to describe the population receiving MTM, describe the services provided, and determine the reimbursement rate for billed MTM services. DATA SOURCES: MTM Current Procedural Terminology (CPT) code claims, electronic medical records, and pharmacist MTM logs. DATA SYNTHESIS: A retrospective review of all MTM charges from January 1, 2010, to March 31, 2010, was performed. Data collected included location of the MTM visit, age, gender, insurance, primary malignancy, comorbidities, home medications, time to complete and document the MTM visit, and rate of reimbursement. RESULTS: In the 3-month period, 239 MTM visits were completed. It took pharmacists a median of 20 minutes (range 15-127) of face-to-face time and 18 minutes (5-90) for documentation per visit. To date, no claims for MTM have been rejected, and reimbursement rates range from 47% to 79% depending on the insurance provider. CONCLUSIONS: MTM in the ambulatory clinic is feasible despite the increase in pharmacist workload from documenting and billing. The increased visibility of clinical pharmacy services justifies the extra time required for formal MTM.

Effect of CYP2D6 polymorphisms on breast cancer recurrence.

BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. METHODS: The authors performed CYP2D6 genotyping from whole blood and fresh frozen tumor samples (n 106) in patients at The University of Texas MD Anderson Cancer Center who were receiving, or had received, tamoxifen as adjuvant therapy for early breast cancer (EBC), using the AmpliChip CYP450 Test. Each patient's medical history was assessed for drugs that affected CYP2D6. Fifty-five patients who had experienced breast cancer recurrence were matched (by date of diagnosis, menopausal status, clinical stage [TNM Staging System], and race) to patients without recurrence. RESULTS: Unadjusted for other patient characteristics, the odds ratio for disease recurrence associated with CYP2D6 functional status was 1.0 (95% confidence interval, 0.35-2.85). After adjustment for stage, CYP2D6 inhibitors (moderate or strong vs none), and follow-up time, no significant association was found between CYP2D6 genotype and breast cancer recurrence in patients who were treated with adjuvant tamoxifen for EBC. CONCLUSIONS: This case-control study demonstrated no significant effect of CYP2D6 genotype on risk of recurrence in breast cancer patients who received adjuvant tamoxifen therapy.

Clinical outcomes of a pharmacist-managed anticoagulation service for breast cancer patients.

PURPOSE: Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS). METHODS: Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005. RESULTS: The median time followed by the AMS was 151 days. Fifty three percent (n = 1651) of total lab draws (n = 3129) were within the target therapeutic INR range 2-3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma). CONCLUSION: To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.

Usage of erythropoiesis-stimulating agents in cancer patients at an academic cancer center and experience with specific care management tools for anemia.

BACKGROUND: In 2007, the US Food and Drug Administration (FDA) issued regulatory alerts for use of erythropoiesis-stimulating agents (ESAs) in cancer patients with anemia after clinical trials and meta-analysis data found that high ESA doses were associated with adverse outcomes in patients. In response to these findings, specific patient management tools for anemia (consisting in an algorithm and prescribing order set) were developed by a multidisciplinary team at The University of Texas MD Anderson Cancer Center. METHODS: A retrospective study consisted of 7117 patients aged 18 years and older with cancer malignancies who had received an ESA between January 2006 and December 2008 at MD Anderson. Changes in utilization of ESAs and packed red blood cells (PRBCs) were evaluated. RESULTS: The number of ESA doses dispensed each month decreased by 83% from January 2006 to December 2008 (P < .01), and the number of patients who received ESAs decreased by 80% (P < .01). The number of dispensed ESA doses for hemoglobin (Hb) levels ≥ 12 g/dL decreased significantly from 4% to 0% (P < .01), and the number for ≥ 10 g/dL decreased from 44% to 12% (P < .01). The PRBC transfusion rate remained stable in solid tumor patients (P > .05) but increased from 7% to 9% (P < .05) in patients with hematologic malignancies. CONCLUSIONS: The authors summarized their experience with use of ESAs in a tertiary oncology center. The implementation of their patient management tools for anemia might have facilitated the observed change at MD Anderson Cancer Center.

Managing cancer treatment-induced bone loss and osteoporosis in patients with breast or prostate cancer.

PURPOSE: To discuss trends in breast and prostate cancer prevalence and survival; risk factors for bone loss, osteoporosis, and fractures and the approach to risk assessment in patients with these malignancies; established and investigational drug therapies for managing cancer treatment-induced bone loss and osteoporosis; and the role of health-system pharmacists in promoting bone health in patients with breast or prostate cancer. SUMMARY: Breast cancer and prostate cancer are common, deadly diseases, but many survivors are alive today because of improvements in early detection and treatment over the past 10-15 years. Cancer chemotherapy, corticosteroids, hormone-ablation therapy, and other common risk factors place patients with breast or prostate cancer at high risk for bone loss, osteoporosis, and fractures. Most patients with breast or prostate cancer should undergo assessment of risk for bone loss and osteoporosis that involves a bone-related history and physical examination, dual-energy X-ray absorptiometry scanning, and the FRAX fracture risk assessment tool from the World Health Organization. A recent National Comprehensive Cancer Network task force report on bone health in cancer care provides recommendations for considering the use of pharmacologic therapy on the basis of the results of this assessment. Bisphosphonates are useful for slowing or preventing bone loss associated with hormone-ablation therapy in women with breast cancer and men with prostate cancer, although fracture data are limited in women and not available in men. The usefulness of other therapies (selective estrogen receptor modulators, teriparatide, calcitonin salmon, and estrogens) is limited by adverse effects, a lack of experience with the drugs in these patient populations, or both. Various drug therapies are in development for managing cancer treatment-induced bone loss and osteoporosis. The agent closest to approval by the Food and Drug Administration, denosumab, has been shown to improve bone mineral density in women and men receiving hormone-ablation therapy for breast or prostate cancer, but additional data are needed to dispel safety concerns that could limit the use of this drug in these patient populations. Health-system pharmacists play an important role in screening patients with a history of breast or prostate cancer for bone loss or osteoporosis, making drug therapy recommendations to address the problem, and counseling patients on modifiable risk factors for osteoporosis and proper use of drug therapies to improve bone health. CONCLUSION: Health-system pharmacists can improve the detection and management of cancer treatment-induced bone loss and osteoporosis in patients receiving systemic therapy for breast or prostate cancer.

The epothilones: how pharmacology relates to clinical utility.

OBJECTIVE: To review the pharmacologic properties of a novel class of chemotherapeutic agents, the epothilones, and to summarize findings from recent clinical trials investigating the various epothilones in cancer therapy. DATA SOURCES: Literature searches were conducted using MEDLINE, PubMed, and the abstract search engines for the American Society of Clinical Oncology and American Association for Cancer Research annual meetings (all searches through November 2008). Primary search terms included epothilone, BMS-247550, ixabepilone, EPO906, patupilone, sagopilone, and ZK-EPO. STUDY SELECTION AND DATA EXTRACTION: Publications were given priority for inclusion if they discussed structural or pharmacologic properties of the epothilones as a class or if they included preclinical or clinical data for epothilones currently in clinical development. DATA SYNTHESIS: The epothilones are a novel class of microtubule-stabilizing agents (MSAs). Epothilones are structurally and pharmacologically distinct from taxanes, but the exact ways in which the pharmacophores of the 2 classes differ has not been firmly established. A number of natural, semisynthetic, and fully synthetic epothilones are in various stages of clinical development. These agents differ from each other and from existing MSAs; these differences influence potency, stability, and solubility. Ixabepilone is currently approved to treat multidrug-resistant metastatic breast cancer and has demonstrated efficacy in earlier stages of breast cancer and in several other tumor types. Patupilone and sagopilone are currently under clinical investigation and have each shown promise in a number of treatment settings and tumor types. All 3 agents appear to be associated with manageable toxicities, but no class-wide toxicity profile exists for the epothilones and dose-limiting toxicities differ among the agents. CONCLUSIONS: The epothilones have demonstrated significant potential for addressing the growing therapeutic challenge of taxane resistance, and the ever-increasing pool of information regarding structure-activity relationships of these MSAs will help to optimize microtubule-targeted chemotherapy.

The optimal therapeutic use of ixabepilone in patients with locally advanced or metastatic breast cancer.

BACKGROUND: The epothilones are a new class of microtubule-stabilizing drugs that exert potent antitumor activity against taxane-resistant and multidrug resistant cell lines. The most clinically advanced member of this class is the semisynthetic epothilone B derivative ixabepilone. PURPOSE: This article reviews the preclinical and clinical data on ixabepilone in patients with locally advanced and metastatic breast cancer (MBC) and provides guidance for pharmacists on its optimal use. DATA SOURCE: PubMed and conference proceedings through August 2008. RESULTS: In preclinical studies, ixabepilone has demonstrated potent antitumor activity and low susceptibility to mechanisms that confer tumor resistance. Clinically meaningful benefits have been achieved with ixabepilone monotherapy in phase 2 trials of patients with MBC who have failed previous chemotherapies (anthracyclines, taxanes, or capecitabine). In a randomized, phase 3 trial, the combination of ixabepilone and capecitabine proved more effective than capecitabine alone after the failure of taxane and anthracycline regimens. At the recommended dose and schedule, the therapeutic ratio of ixabepilone is generally favorable, and its adverse effects (notably neutropenia and peripheral neuropathy) are generally manageable and reversible. CONCLUSION: Ixabepilone represents an advance in the treatment of anthracycline - and taxane-pretreated MBC. Future studies will define its efficacy in combination with other drugs used in the treatment of MBC, as well as in other types of cancer.

Treatment-experienced breast cancer.

PURPOSE: Breast cancer, the second leading cause of cancer mortality among women in the U.S., following lung cancer is described and the number of treatment options for patients with breast cancer, which has been accompanied by a trend toward declining cancer mortality, is reviewed. SUMMARY: Despite these advances in cancer therapy, many patients with early stage breast cancer eventually progress to metastatic disease. Several prognostic factors have been identified for patients with metastatic breast cancer, including tumor volume and location, comorbid conditions, response to prior therapy, and the presence of molecular tumor markers (e.g., estrogen receptors [ER] and human epidermal growth factor receptor 2 [HER2]). Metastatic breast cancer is usually incurable, and the goals of therapy are palliation of symptoms, extending survival, and improving quality of life. Options for the medical management of metastatic breast cancer include endocrine therapy, cytotoxic chemotherapy, and targeted biologic agents. Treatment guidelines developed by the National Comprehensive Cancer Network generally recommend endocrine therapy for patients with ER-positive or progesterone receptor (PR)-positive disease, for patients with bone or soft tissue metastasis, or those with asymptomatic visceral disease. Cytotoxic chemotherapy alone is usually recommended for patients with ER-negative/PR-negative disease, who have symptomatic visceral disease, or whose tumors are HER2-negative or rapidly growing. Biologic agents (e.g., trastuzumab and lapatinib) alone or in combination are recommended for patients with HER2-positive disease. CONCLUSION: Treatment options for meta-static breast cancer continue to increase as new antitumor medications enter clinical practice and controlled clinical trials evaluate the optimal combinations of established and novel medications.