Purpose Hyperhydration and urinary alkalinization is implemented with all high-dose (HD)-methotrexate infusions to promote excretion and prevent precipitation of methotrexate in the renal tubules. Our institution utilized enteral alkalinizing agents (sodium bicarbonate tablets and sodium citrate/citric acid solution) to alkalinize the urine of patients receiving HD-methotrexate during a parenteral sodium bicarbonate and sodium acetate shortage. The purpose of this study is to establish the safety and efficacy of the enteral route for urine alkalinization. Methods A single-center, retrospective, cohort study was conducted comparing cycles of HD-methotrexate using enteral alkalinizing agents to parenteral sodium bicarbonate. The primary objective was to compare the time, in hours, from administration of first inpatient administered dose of alkalinizing agent to time of achieving goal urine pH. Secondary objectives evaluated total dose of sodium bicarbonate required to achieve goal urine pH, time from start of urine alkalinizing agent until time of achieving methotrexate level safe for discharge, and toxicities associated with methotrexate and the alkalinizing agents. Results A total of 118 patients were included in this study, equally divided into two cohorts based on parenteral versus enteral routes of administration. No statistical difference was determined between the two cohorts regarding time to goal urine pH (6.5 h versus 7.9 h, P = 0.051) or regarding time to methotrexate level deemed safe for discharge (63.5 h versus 62.5 h, p = 0.835). There were no significant differences in methotrexate-induced toxicities. Conclusion Our study found enteral routes of urine alkalinization to be a viable alternative to the traditional parenteral sodium bicarbonate, especially during parenteral sodium bicarbonate and acetate shortages.
The rise in non-AIDS defining cancers (NADCs) is emerging as a leading cause of death for HIV and cancer patients. To address this, current literature and guidelines suggest the continuation of antiretroviral therapy (ART) with oral oncolytic agents to prevent adverse complications associated with HIV disease progression. However, such an approach has the potential for drug–drug interactions and adverse events for patients on such therapy. Further, recommendations on how to adjust these medications, when used concomitantly, are limited. As such, our purpose is to evaluate existing literature through such means as drug databases (e.g. Micromedex, Lexi-Comp, etc.) and package inserts along with PubMed/Medline, Embase, and Google Scholar databases to develop a reference tool for providers to utilize when there is a decision to treat a patient with ART and oral oncolytic agents concurrently. Our findings suggest that there are many drug interactions that should be taken into consideration with dual therapy. Metabolism is a key determinant of dose adjustment, and many oncolytic agents and ART agents must have their dose adjusted as such. Most notably, several tyrosine kinase inhibitors require dose increases when used with non-nucleoside reverse transcriptase inhibitors (NNRTIs) but must be decreased when used concomitantly with protease inhibitors (PIs) and cobicistat. Further findings suggest that certain agents should not be used together, which include, but are not limited to, such combinations as bosutinib with NNRTIs, cobicistat, or PIs; idelalisib with maraviroc or PIs; neratinib with NNRTIs, cobicistat, or PIs; and venetoclax with NNRTIs. Overall, the most prominent oncolytic drug interactions were discovered when such agents were used concomitantly with PIs, cobicistat-boosted elvitegravir, or NNRTIs. Future studies are necessary to further evaluate the use of these agents together in disease therapy to generate absolute evidence of such findings. However, from the studies evaluated, much evidence exists to suggest that concomitant therapy is not without drug interactions. As such, clinical decisions regarding concomitant therapy should be evaluated in which the risk and benefit of dual therapy are assessed. Dose adjustments must be made accordingly and in consultation with both HIV and oncology clinicians and pharmacists to reduce the risk for adverse outcomes and disease progression for those with cancer and HIV/AIDS.
Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200-500 mg/m/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580-3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m or 400 mg/m dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.
PURPOSE. A stepwise approach to development and implementation of a program to standardize and increase pharmacists' involvement in anticoagulation therapy at a large academic medical center is described. SUMMARY. In response to the Joint Commission's national goal of improved patient safety in anticoagulation therapy, a work group of pharmacy administrators, educators, clinical specialists, and decentralized pharmacists at the hospital developed the structure for a comprehensive inpatient anticoagulation program (IAP); the work group also developed a list of required competencies, educational materials, assessment methods, and mechanisms for eliciting feedback from IAP pharmacists and other patient care staff. After completion of training that included structured case-review sessions, a one-on-one shadowing experience, and competency assessment, IAP pharmacists began reviewing clinical and laboratory data on patients receiving warfarin and low-molecular-weight heparins and providing recommendations to physicians, nurse practitioners, and other health care team members. Feedback from other clinicians was generally positive, with a majority of those surveyed indicating that increased pharmacist involvement in anticoagulation monitoring and dosage adjustment resulted in improved patient care; about 80% indicated that they concurred with pharmacists' recommendations at least 75% of the time. Results of a survey of IAP pharmacists indicated increased satisfaction with their daily duties but also a need for improved pharmacist-to-pharmacist communication. CONCLUSION. Case-based advanced training and implementation of an IAP in a tertiary care hospital increased pharmacists' involvement in the management of inpatients receiving anticoagulants.
Objective Patients who have an up-to-date and accurate medication list are less susceptible to medication errors and allow care teams to make more informed treatment decisions. Through utilizing student pharmacists to provide medication history services, we anticipate improved patient safety and overall quality of patient care. The purpose of this project was to implement a medication history service for ambulatory oncology patients of the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital. Methods A phased approach was utilized to implement a standardized operating procedure for completing medication histories in ambulatory oncology patients. Data collection included number of total medication discrepancies, percentage of patients with high-risk medications, and high-risk medication classes involved in discrepancies. Additionally, time data were collected, including time spent calling the patient, completing patient work up, and preceptor oversight. Results Students completed medication histories for 60 patients; 83% of patients had at least one discrepancy with 21% of those discrepancies involving a high-risk medication. High-risk medications involved in discrepancies included oral chemotherapeutic agents, anticoagulants, insulin, and opioids. Conclusion The majority of patients seen had at least one medication discrepancy that was identified and corrected through the medication history service. By correcting the discrepancy, the likelihood of medication errors occurring was decreased. Continuous workflow changes are being made to identify the number and type of resources to expand the service to all appropriate ambulatory oncology patients at the Sidney Kimmel Comprehensive Cancer Center.
Axitinib is a vascular endothelial growth factor receptor inhibitor indicated for advanced renal cell cancer after failure of one prior systemic therapy. We report a case where a patient receiving axitinib experienced a supratherapeutic INR soon after initiation of an age-appropriate warfarin dose. We propose two possible mechanisms for this interaction, including competitive protein binding and decreased metabolism. Close INR monitoring and dose adjustments of warfarin may be necessary in patients receiving concomitant axitinib and warfarin in order to decrease the risks associated with this interaction.
Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m/dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.
Venous thromboembolism (VTE) is a significant but preventable cause of hospital-related morbidity and mortality. Prevention of in-hospital VTE, thus, has become a major quality improvement initiative within hospitals. However, addressing VTE prophylaxis rates and appropriateness on transition to other facilities has not been fully characterized to date. The authors of this study retrospectively evaluated VTE prophylaxis on transfer from medical inpatient settings to long-term care facilities. Analysis indicated that on transfer to other facilities, VTE prophylaxis recommendations were not routinely documented. Interfacility communication is crucial to ensure that appropriate prophylaxis recommendations are addressed during transitions of care. New processes evaluating VTE prophylaxis recommendations at the time of care transfer warrant further study.
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