Carboplatin desensitization - simplified 4-step 2-bag method.

INTRODUCTION: Our cancer program adopted a method for carboplatin desensitization (4-step 2-bag method) that administers the same intensity of drug exposure with a simplified approach to product management in comparison to a published protocol (4-step 4-bag method). METHODS: The intensity of carboplatin administration for 1:1,000, 1:100, 1:10, and 1:1 dilutions and concomitant fluid administration were compared for the 4-step 2-bag (bags A, B) and 4-step 4-bag (bags 1, 2, 3, 4) methods. Pharmacy preparation of bags A and B is described. A succinct overview of the desensitization procedure is provided. Important considerations germane to pharmacy practice are presented. Chart review of patients who underwent carboplatin desensitization with the 4-step 2-bag method between 7/13/2021 and 11/22/2023 was performed to demonstrate institutional use. RESULTS: The 4-step 2-bag method delivers similar rates of drug intensity from start of desensitization to completion of the planned dose as the previously published 4-step 4-bag method. Accuracy of regimen-based dose administration is assured by infusion of bag B contents irrespective of infusion interruptions or rate changes necessitated by patient tolerance. Bag A provides the 1:1000 dilution in a pharmaceutically elegant manner using administration rates and volumes compatible with clinical practice. CONCLUSION: The 4-step 2-bag method for carboplatin desensitization administers controlled drug titration corresponding to 1:1000, 1:100, 1:10, and 1:1 dilutions for dose administration using two compounded admixture bags. Inaugural clinical use of the 4-step 2-bag method for carboplatin desensitization at our healthcare facility has proceeded with expected patient tolerance.

Loncastuximab tesirine: Risk for dose variance.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Elotuzumab: Empiric analysis of dexamethasone administration schedule.

Elotuzumab in combination with dexamethasone and immunomodulating agents (IMiDs) lenalidomide or pomalidomide is 2nd to 4th line therapy for multiple myeloma. The labelled dosage of dexamethasone for use in conjunction with elotuzumab and IMiDs splits the dexamethasone dose into two administrations, one oral and one intravenous, on the days of each elotuzumab infusion. Administration of split dose dexamethasone on days of elotuzumab administration is based on the registration trials submitted for drug approval and was intended to ensure standard well-timed immunotherapy premedication using pharmacologically equivalent dexamethasone doses for both study arms. Administration of dexamethasone in the manner delineated by the elotuzumab product label adds complexity to the delivery of care. This commentary provides an empirical assessment of established medication safety and effectiveness which supports administration of dexamethasone standard intermittent dose instead of the split dose approach delineated on elotuzumab package insert. Simplification of regimen administration improves medication adherence, reduces the risk of inadvertent omission or duplication of medication therapy, and improves the workflow required for delivery of care.

International Society of Oncology Pharmacy Practitioners (ISOPP) position statement: Role of the oncology pharmacy team in cancer care.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT. This position statement advocates that: 1) the OPT be fully incorporated into the MHT to optimize patient care; 2) educational and healthcare institutions develop programs to continually educate OPT members; and 3) regulatory authorities develop certification programs to recognize the unique contributions of the OPT in cancer patient care.

Intravenous Lidocaine Administered as Twice Daily Bolus and Continuous Infusion for Intractable Cancer Pain and Wound Care Pain.

INTRODUCTION: Intravenous lidocaine is an option for intractable pain caused by advancing cancer and wound care. We report a case of intractable cancer pain and wound care pain managed with concurrent use of lidocaine administered as a twice daily intravenous bolus in addition to continuous intravenous infusion. CASE DESCRIPTION: A 31-year-old male with rapidly progressing locally advanced squamous cell cancer affecting the gluteal area developed extensive painful and purulent ulcerating wounds affecting the coccyx, superior gluteal cleft, and buttocks. Laboratory tests were within normal limits, except for low albumin results. The patient's Palliative Performance Score was 60%. A trial of intravenous lidocaine 150 mg administered twice daily before dressing changes improved analgesia according to the patient's report. For additional improvement, a continuous intravenous infusion of lidocaine 1 mg/minute was initiated, in addition to the twice daily bolus infusions of lidocaine. The patient's pain score with dressing changes improved from 8-10 of 10 to 4-5 of 10 within 24 hours after initiation of the continuous intravenous lidocaine infusion. Lidocaine infusion was administered for a period of 45 days with targeted lidocaine blood levels not exceeding 5 mcg/mL. Twice daily lidocaine bolus infusions before dressing changes were administered for a total duration of 63 days. The lidocaine continuous intravenous infusion was discontinued on day 45 of therapy as a potential contributing factor to central nervous system adverse effects and in anticipation of transition to a subacute rehabilitation facility. DISCUSSION: Intravenous lidocaine added to the efficacy of standard analgesic medications and nerve block procedures in our patient. This case demonstrates increasing blood lidocaine levels with continuous intravenous infusion despite stable clinical parameters and laboratory markers of major organ function. Monitoring lidocaine levels is a prudent course of action to identify drug accumulation with administration of lidocaine by continuous intravenous infusion.

Cost avoidance from dose rounding biologic and cytotoxic antineoplastics.

Background To reduce product wastage, our institution allows automatic dose rounding of biologic and cytotoxic anticancer agents. The purpose of this project was to determine the actual annual cost avoidance due to pharmacist-managed automatic dose rounding of anticancer treatments. Methods Financial impact was assessed within the context of our departmental standard work which supports automatic dose rounding of biologic anticancer agents (±10%) and cytotoxic anticancer agents (±5%) to the nearest vial size for body surface area- or weight-based doses. Exclusions to automatic dose rounding include multiple dose vial products, pediatric orders, clinical trial drugs, and parenteral busulfan. The amount of cost avoidance for each rounded dose was determined using the product acquisition cost of the smallest available product amount. Data were collected from anticancer treatment orders for the fiscal year 1 July 2013 to 30 June 2014. Results A total of 6216 doses of anticancer drugs were checked for dose rounding during the period of data collection. Almost $200,000 in product acquisition cost was avoided with pharmacist-managed automatic dose rounding. Six different biologic products accounted for approximately 7% of the total doses analyzed and 78% of the cost avoidance. Fifteen drugs comprised the array of cytotoxic agents rounded. Approximately, 37% and 4% of the biologic and cytotoxic doses were rounded up to the vial size. Conclusion Routine dose rounding of biologic anticancer agents (±10%) and cytotoxic products (±5%) achieved cost avoidance through reduction of drug wastage at our institution.

Effect of single agent high-dose methotrexate-related acute kidney injury on length of hospitalization and relative dose intensity in adult patients with central nervous system lymphoma.

Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student's t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.

Stability of i.v. admixture containing metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate in 0.9% sodium chloride injection.

PURPOSE: The chemical stability of a sterile admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was evaluated. METHODS: Triplicate samples were prepared and stored at room temperature without light protection for a total of 48 hours. Aliquots from each sample were tested for chemical stability immediately after preparation and at 1, 4, 8, 24, and 48 hours using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate were selectively monitored using multiple-reaction monitoring. Samples were diluted differently for quantitation using three individual LC-MS/MS methods. To determine the drug concentration of the three compounds in the samples, three calibration curves were constructed by plotting the peak area or the peak area ratio versus the concentration of the calibration standards of each tested compound. Apixaban was used as an internal standard. Linearity of the calibration curve was evaluated by the correlation coefficient r(2). RESULTS: Constituents of the admixture of metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection retained more than 90% of their initial concentrations over 48 hours of storage at room temperature without protection from light. The observed variability in concentrations of these three compounds was within the limits of assay variability. CONCLUSION: An i.v. admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was chemically stable for 48 hours when stored at room temperature without light protection.

Improved pharmacy department workflow with new method of order entry for single-agent, high-dose methotrexate.

PURPOSE: To determine whether a process change impacted the proportion of orders for single-agent, high-dose methotrexate entered by chemotherapy pharmacists instead of general pharmacy staff. Coordination of antiemetic premedication and leucovorin rescue with the new method of order entry was evaluated. METHODS: Adults treated with single-agent, high-dose methotrexate were identified retrospectively. Order entry of methotrexate and ancillary medications was examined to determine whether the old or new method was used and whether it was performed by a chemotherapy pharmacist. The fundamental difference between the old and new methods for order entry is use of the "unscheduled" frequency of medication administration to replace the administration frequency of "once" with a specified date and time. Timing of antiemetic premedication and leucovorin rescue relative to methotrexate administration were tallied for the new method. Chi-square analysis was performed for the primary objective. Observational statistics were performed otherwise. RESULTS: The number of evaluable encounters identified was 158. A chemotherapy pharmacist entered a greater proportion of orders when the new method was utilized (P < .0001). The proportion of orders entered by a chemotherapy pharmacist increased during the hours of 0700 and 2259 with the new method. Appropriate coordination of antiemetic and leucovorin administration was documented for 96% and 100% of cases with the new method of order entry. CONCLUSION: The proportion of orders for single-agent, high-dose methotrexate entered by a chemotherapy pharmacist was significantly greater with the use of the new method. Administration of antiemetic premedication and leucovorin rescue were appropriately coordinated with the use of the new method for order entry of single-agent, high-dose methotrexate.

Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate.

PURPOSE: Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. METHODS: Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. RESULTS: The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. CONCLUSION: At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

Pseudohyperkalemia in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome.

PURPOSE: Recognition of pseudohyperkalemia is essential to prevent medical mismanagement of erroneous hyperkalemia. The purpose of this case is to describe pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. Methods for determination of pseudohyperkalemia are discussed. SUMMARY: A 75-year-old male with progressive chronic lymphoblastic leukemia was hospitalized for medical evaluation and chemotherapy administration. Notable laboratory findings included white blood cell count of 479 × 10(3) cells/µL (4.00 × 10(3) cells/µL-10.80 × 10(3) cells/µL) with 95% lymphocytes (20%-50%) and 5% blasts (zero) present in the differential, serum potassium 9.8 mM/L (3.4 mM/L-5.0 mM/L), uric acid of 11.8 mg/dL (3.5 mg/dL-8.0 mg/dL), serum creatinine 1.47 mg/dL (0.60 mg/dL-1.30 mg/dL), and lactate dehydrogenase of 2529 IU/L (100 IU/L-220 IU/L). The patient was anemic (Hb 7.6 g/dL (14.0 g/dL-18.0 g/dL)) and thrombocytopenic (17 × 10(3) platelets/µL (140 × 10(3) platelets/µL-400 × 10(3) platelets/µL)). There were no electrocardiographic findings indicating systemic hyperkalemia. Repeat analysis of the blood potassium level using a heparinized tube assayed immediately after specimen collection demonstrated a plasma potassium level 4.1 mM/L. Subsequent analysis of specimens using similar methodology demonstrated potassium results within the normal limits despite continued laboratory evidence of pseudohyperkalemia. Based on the patient's conscious and interactive condition, ECG findings, and normal plasma potassium level following immediate analysis, the diagnosis of pseudohyperkalemia was made. Laboratory findings of pseudohyperkalemia persisted throughout the period of leukocytosis. CONCLUSION: This case describes pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia (CLL). Practitioners should consider pseudohyperkalemia as the underlying cause of elevated potassium levels in patients with malignant leucocytosis who do not have signs or symptoms of systemic hyperkalemia.

Clofarabine-associated acute kidney injury and proteinuria.

Clofarabine is used as second-line therapy for acute myeloid leukemia. Acute renal impairment is reported with clofarabine; however, it is more likely to occur in patients with confounding factors that may underlie the adverse event. We describe a 65-year-old man treated with clofarabine for relapsed acute myeloid leukemia who experienced severe acute kidney injury and proteinuria temporally related to clofarabine administration. The morning after completion of clofarabine administration, his serum creatinine concentration increased to approximately 1.4-fold above his baseline value, and peaked at 2.8-3.6-fold over baseline within 72 hours. A 24-hour urine collection contained 4100 mg of protein. His serum creatinine concentration gradually returned to within 1.5 times his baseline value. Examination of the patient's clinical course, vital signs, and laboratory results did not yield any compelling evidence of alternative causes for acute kidney injury. The patient's comorbidities included a left ventricular ejection fraction of 35-40% and diabetes mellitus. His drug therapy with potential renal effects-lisinopril, furosemide, tobramycin, allopurinol, and valacyclovir-that preceded clofarabine administration was evaluated, and none was determined to be a major factor in the development of this adverse event. Bone marrow evaluations were negative for residual leukemia after clofarabine therapy. After approximately 11 weeks of hospitalization, the patient and his family made an informed decision to continue supportive care at home. Acute kidney injury in this patient was attributed to clofarabine administration due to the time course of events with respect to potential contributing factors. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of renal effects and clofarabine therapy. To our knowledge, this is the first report of medically significant proteinuria associated with administration of clofarabine. Clinicians should be aware of the potential for acute kidney injury if their patients are administered clofarabine.

Cost savings from dose rounding of biologic anticancer agents in adults.

PURPOSE: The purpose of this project was to determine the cost savings related to a dose-rounding process for adult biologic anticancer agents. METHODS: Biologic anticancer agents prepared by the inpatient pharmacy were identified retrospectively through completed chemotherapy preparation checklists and medication orders on file in the pharmacy or by the clinical pharmacist for adult oncology from the medical records of patients in her practice. The specific products screened for evaluation were aldesleukin, bevacizumab, cetuximab, denileukin diftitox, gemtuzumab, rituximab, and trastuzumab. Data collected included drug name, ordered dose, rounded dose, and product vials not wasted. Specific drug costs were provided by the department's purchasing office. The project was reviewed and approved by the institutional review board to allow retrospective data collection from patient records. Cost savings were evaluated retrospectively for the time period of January 1, 2005 through March 31, 2005. RESULTS: One hundred and twenty-six orders for biologic anticancer agents were processed by the pharmacy department during the 3-month time period of data collection. Dose rounding could reduce drug wastage for 42% of these orders. Potential cost savings from dose rounding was $24,434 for the 3-month interval evaluated. However, nonadherence to dose rounding for 29 rituximab orders decreased the actual cost savings to $15,922. Individual staff education was reinforced to address nonadherence. CONCLUSION: Routine dose rounding of biologic anticancer agents to an amount within 10% of the ordered dose achieved cost savings through reduction of drug wastage at our institution.

Anticholinergic medications for managing noisy respirations in adult hospice patients.

PURPOSE: Anticholinergic medications for reducing noisy respirations in adult hospice patients are evaluated. SUMMARY: Anticholinergic medications used to reduce noisy respirations from retained secretions in terminal patients include atropine, glycopyrrolate, scopolamine, and scopolamine derivatives. Pharmaceutical anticholinergic treatment of retained secretions in hospice patients was evaluated in six studies, three of which compared the efficacy of glycopyrrolate to scopolamine in actively dying patients. Subcutaneous glycopyrrolate, scopolamine hydrobromide, and scopolamine butylbromide were similar in their ability to reduce noisy respirations overall and lower and the level of distress exhibited by family members and visitors. Two of the six studies compared the efficacy of medication therapy after institutional formulary changes from scopolamine to glycopyrrolate. The same dosages of subcutaneous glycopyrrolate and scopolamine, which delivered an initial bolus followed by continuous infusion, were reported in each study. Both studies concluded that there was equivalent efficacy between the two products. One study reported a more rapid response in patients treated with glycopyrrolate. In comparison, the last study reported more rapid responses in patients who received scopolamine compared with patients who received glycopyrrolate. Retrospective reports described symptom improvement with parenteral scopolamine in most patients. CONCLUSION: Parenteral and transdermal anticholinergic medications are useful for the reduction of noisy respirations in hospitalized hospice patients. Difficult administration makes oral and sublingual products less desirable for use in this population.

Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer.

Prostate cancer is the leading cancer diagnosis and second leading cause of cancer-related mortality for men in the United States. Due to the increased prevalence of prostate cancer in men older than 50 years, men at risk for prostate cancer represent the same population of men who are at greatest risk for metabolic syndrome, diabetes mellitus, and coronary artery disease (CAD). In addition to risk factors for CAD that are applicable to the general population, men with prostate cancer can be at increased risk for CAD due to long-term androgen deprivation therapy (ADT) administered as treatment for prostate cancer. Men undergo ADT by medical (drug therapy) or surgical (castration) means. Luteinizing hormone-releasing hormone (LHRH) agonists are the primary drug therapies used for ADT. Commercially available LHRH agonists are goserelin, histrelin, leuprolide, and triptorelin. Body composition changes, hyperlipidemia, insulin resistance, metabolic syndrome, and acute coronary syndrome are all reported adverse effects of ADT, which are consequences of reduced levels of circulating testosterone. Metabolic and body composition changes associated with ADT arise within months of beginning medical ADT and persist after discontinuation of therapy. To better understand the increased risk of metabolic syndrome, diabetes, and heart disease in patients undergoing ADT for prostate cancer, we performed a MEDLINE search (1986-2008) to identify pertinent studies and reports. Additional citations were obtained from the articles retrieved from the literature search. We found that the increased risk for serious cardiovascular disease becomes evident within months of beginning ADT. Pharmacists should provide counseling to these patients on primary disease prevention. Men receiving ADT should be monitored routinely for signs and symptoms of metabolic syndrome, diabetes, and CAD. Healthy lifestyle practices should be encouraged, and physical therapy should be considered for these patients.

Docetaxel-associated epiphora.

Docetaxel is a semisynthetic taxane indicated for the treatment of advanced breast, prostate, and non-small cell lung cancers; it is also used for the treatment of various other solid tumors. The standard intermittent dosage of docetaxel is 60-100 mg/m2 every 3 weeks. At this dose and schedule, myelosuppression is common and neutropenia is usually the dose-limiting toxicity. Weekly administration of docetaxel 20-42 mg/m2 is being tested in the treatment of advanced solid tumors in order to improve patient tolerance by reducing the interval dose and to maintain therapeutic efficacy by increasing overall dose intensity. Asthenia and peripheral neuropathy can limit continued administration of weekly docetaxel. Epiphora (excess tearing due to narrowing or blockage of the lacrimal outflow passages) is associated with repeated weekly administration of docetaxel. This adverse effect can interfere with activities of daily life and negatively affect quality of life. Epiphora may be an underreported adverse effect of treatment because of underrecognition by clinicians and patient embarrassment with respect to seemingly uncontrolled tearing. The use of weekly docetaxel administration is expanding; therefore, patients should be educated to recognize and report signs and symptoms of epiphora. It is important for clinicians participating in the care of patients undergoing treatment with docetaxel to monitor for excess tearing and signs of eye irritation to ensure timely management of treatment-related epiphora.