Safety and efficacy of a urine alkalinization protocol developed for high-dose methotrexate patients during intravenous bicarbonate shortage

2019 ◽  
Vol 25 (8) ◽  
pp. 1860-1866 ◽  
Author(s):  
Amanda M Roy ◽  
Matthew Lei ◽  
Uvette Lou
Keyword(s):  
Sodium Bicarbonate ◽  
Creatinine Clearance ◽  
Urine Output ◽  
Retrospective Chart Review ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Urine Ph ◽  
Dose Methotrexate ◽  
Mean Time ◽  
Intravenous Sodium

Purpose Urinary alkalinization with intravenous sodium bicarbonate is standard during high-dose methotrexate administration. Due to a national intravenous sodium bicarbonate shortage, a urinary alkalinization protocol involving hyperhydration with intravenous fluids, oral bicarbonate, and intravenous or oral acetazolamide was utilized from 10 April to 30 May 2017 (“shortage protocol”). This study compared outcomes between protocols. Methods A single-center, retrospective chart review was conducted for adults who received methotrexate ≥500 mg/m2 on ≥ two occasions, at least once during each protocol, between 19 February and 19 July 2017. Results Eighteen patients (50% male), median age 65 years, received 76 total high-dose methotrexate cycles. Shortage protocol was used in 37 cycles (48.7%). Mean time to methotrexate clearance did not differ between groups (p = ns). Mean time to urinary alkalinization and duration of hospitalization were not statistically different (p = 0.49 and 0.23, respectively). Average total bicarbonate administered per 24 hours was higher in standard protocol (p < 0.05), but hydration rates were similar (p = 0.73). Creatinine clearance and urine output on days 1 and 2 post-high-dose methotrexate did not significantly differ (creatinine clearance day 1, p = 0.27; creatinine clearance day 2, p = 0.55; urine output day 1, p = 0.62; urine output day 2, p = 0.60). Interruptions in alkalinization were significantly higher during shortage (0.41 ± 0.75 instances of urine pH < 7 during standard vs. 1.3 ± 1.7 under shortage, p < 0.05).

Retrospective evaluation of sodium acetate use for urine alkalinization in patients receiving high dose methotrexate

2021 ◽  
pp. 107815522110602
Author(s):  
Cassandra L Perkey ◽  
Laura A Flynn ◽  
Katie Lentz ◽  
Sara Butler
Keyword(s):  
Sodium Bicarbonate ◽  
Sodium Acetate ◽  
Similar Efficacy ◽  
Primary Objective ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Efficacy And Safety ◽  
Dose Methotrexate ◽  
Urine Alkalinization ◽  
Intravenous Sodium

Purpose Methotrexate is an antifolate agent used in treatment of several malignancies. Many toxicities accompany methotrexate that are minimized with urine alkalinization. Parenteral sodium bicarbonate is the historical standard alkalinizing agent, but use has been limited by intermittent shortages. However, intravenous sodium acetate may be considered as a chemically equivalent alternative. The primary objective of this study is to determine the efficacy of sodium acetate versus sodium bicarbonate for urine alkalinization for high-dose methotrexate (HDMTX). Methods This is a retrospective cohort study including adults admitted to Barnes-Jewish Hospital to receive HDMTX for lymphoma, breast cancer with leptomeningial spread, or osteosarcoma. Patients must have received intravenous sodium acetate or sodium bicarbonate alkalinization. Results Of 192 HDMTX encounters, 154 (sodium bicarbonate, n = 86; sodium acetate, n = 68) were evaluated for efficacy and safety. Safety outcomes were not significantly different between groups except for higher peak methotrexate level in the bicarbonate group (2.9 mcmol/L vs. 1.7 mcmol/L, p = 0.023), and increased incidence of grade 3–4 ALT in the sodium bicarbonate group (23.5% vs. 9%, p = 0.02). Time from alkalinizer initiation to pH ≥7 was significantly shorter with sodium bicarbonate (4 vs. 5.15 h, p = 0.021). Nonetheless, outcomes such as length of stay (4.4 vs. 4 days respectively, p = 0.037) and time to methotrexate clearance (3.6 vs. 3.2 days respectively, p = 0.023) reveal that inpatient time was shorter with sodium acetate overall. Conclusion This retrospective analysis suggests that sodium acetate has similar efficacy and safety to sodium bicarbonate for alkalinization and may be considered as an alternative in future shortage situations.

scholarly journals Evaluation of an Oral Sodium Bicarbonate Protocol for High-Dose Methotrexate Urine Alkalinization

2021 ◽  
Author(s):  
Rachel Heisler ◽  
Jordan Kelly ◽  
Sara Abedinzadegan Abdi ◽  
Jennifer Hawker ◽  
Leanne Fong ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Sodium Bicarbonate ◽  
Retrospective Chart Review ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Urine Alkalinization ◽  
Nausea And Emesis ◽  
Alberta Health ◽  
Oral Sodium

Abstract Purpose: Intravenous (IV) sodium bicarbonate is considered standard therapy for high-dose methotrexate (HDMTX) urine alkalinization. Due to a national IV sodium bicarbonate shortage, an oral (PO) sodium bicarbonate protocol was implemented by Alberta Health Services (AHS) for HDMTX urine alkalinization. This study aims to evaluate the efficacy and safety of the PO sodium bicarbonate protocol compared to IV sodium bicarbonate for HDMTX urine alkalinization. Methods: A retrospective chart review of adult patients who received HDMTX (>500 mg/m2) with sodium bicarbonate for urine alkalinization at 4 hospitals in Alberta was conducted. Patients who received IV sodium bicarbonate between January-June 2017 and PO sodium bicarbonate between July-December 2017 were compared for the primary outcome of time to methotrexate clearance. Results: A total of 84 and 78 HDMTX cycles were included in the IV and PO cohorts, respectively. No difference in time to methotrexate clearance was seen between the IV and PO cohorts, 91.6 (± 35.4) hours and 95.2 (± 44) hours respectively; p=0.5. The proportion of HDMTX cycles that experienced a >25% increase in serum creatinine was not statistically significant, IV protocol 12% and PO protocol 5%; p=0.13. Nausea and emesis occurred more frequently in the PO cohort than the IV cohort, though rarely resulted in refused doses or change to alternate sodium bicarbonate formulations.Conclusions: The results of this study indicate that the AHS PO sodium bicarbonate protocol was no different in time to methotrexate clearance or rates of increased serum creatinine when compared to IV sodium bicarbonate.

scholarly journals Oral Regimen for Urine Alkalization in Patients Receiving High Dose Methotrexate during a National Shortage of Intravenous Sodium Bicarbonate

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2309-2309 ◽  
Author(s):  
Daniel R Reed ◽  
Jeremy M Sen ◽  
Eric J Pierce ◽  
Maria C Nicolais ◽  
Michael K Keng
Keyword(s):  
Length Of Stay ◽  
Sodium Bicarbonate ◽  
Categorical Variables ◽  
Published Data ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Start Time ◽  
Urine Ph ◽  
Dose Methotrexate ◽  
The Impact

Abstract Background: High dose methotrexate (MTX) is an important agent in the prevention and treatment of cancer in the central nervous system. Administration of this drug requires alkalization of the urine, which traditionally includes the use of intravenous (IV) sodium bicarbonate (bicarb). In May 2017, IV bicarb was on national shortage; at the University of Virginia, pharmacists and physicians designed an oral (PO) regimen using bicarb and acetazolamide to ensure patients could continue receiving MTX. As there are limited published data, we aimed to assess the safety and the impact on time to start of MTX. Methods: Retrospective chart review was done 5/2016-4/2017 to establish a baseline time to methotrexate. In a prospective analysis, data was collected from May 2017 to May 2018 on all patients who received MTX. For patients receiving the PO regimen, bicarb 2,600 mg PO 6 times daily and acetazolamide 250 mg PO every 6 hours were the initial doses and titrated to maintain a urine pH greater than or equal to 7. The primary endpoint was time to MTX for patients with planned admissions who start MTX upon meeting urine pH and output parameters. Secondary endpoints included incidence of acute kidney injury (AKI) and delayed methotrexate clearance for all patient encounters. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Delayed MTX clearance was defined based on failure to meet goal levels based on published chemotherapy protocols. χ2 analysis was completed on categorical variables. A statistical process control chart (p-chart) depicted time to MTX. Results: A total of 162 patient encounters were included in the analysis. The median age of patients receiving oral bicarb was 51 years (range 21-69) and was 51 years (range 21-63) for patients receiving IV bicarb. Eighty-six encounters were planned admissions that started MTX when urine parameters were met and received either IV (n=32) or PO bicarb (n=54). In these patients median time from admission to MTX was 8.4 vs 7.9 hours, respectively. Figure 1 shows consecutive patients receiving MTX prior to, during, and after resolution of the IV bicarb shortage; there is less variability and fewer outliers in the MTX start time when exclusively administering the PO regimen during the shortage. For the secondary analysis an additional 76 encounters with either unplanned admissions or predetermined MTX start time on subsequent day to admission were analyzed for safety outcomes. The rate of AKI was 14.5% vs 8.9% in the PO vs IV groups, respectively (p=0.28). There was no difference in incidence of delayed methotrexate clearance with 26.5% of patients in PO group vs 25.3% patients in IV group (p=0.87). Length of stay was slightly increased in patients who received PO vs IV alkalization (3.78 vs 3.15 days). Conclusion: Our alternative oral bicarb and acetazolamide urine alkalization regimen appears safe in patients receiving MTX and allowed for continued treatment of patients during a national IV bicarb shortage. Time to start of MTX was decreased with implementation of PO regimen, and there appeared to be a more predictable start time for MTX. While not significant, the higher incidence of AKI in PO group warrants further analysis. Future efforts include using oral outpatient alkalization prior to inpatient admission to work towards improving length of stay. Disclosures No relevant conflicts of interest to declare.

scholarly journals A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration

2017 ◽  
Vol 25 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Zak Cerminara ◽  
Alison Duffy ◽  
Jennifer Nishioka ◽  
James Trovato ◽  
Steven Gilmore
Keyword(s):  
Medical Center ◽  
Cost Savings ◽  
Retrospective Chart Review ◽  
Patient Characteristics ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Protocol Implementation ◽  
Dose Methotrexate ◽  
Before And After ◽  
The Cost

Background Methotrexate has a wide dosing range. High-dose methotrexate is a dose of 1000 mg/m2 or greater. In the 1970s, the incidence of mortality associated with High-dose methotrexate ranged from 4.6 to 6%. In 2012, the University of Maryland Medical Center implemented a standardized high-dose methotrexate protocol. The purpose of this study was to evaluate whether the institution followed recommendations based on the Bleyer nomogram for the administration of high-dose methotrexate more closely after the implementation of the protocol. Methods In this retrospective chart review, 37 patients received 119 cycles of high-dose methotrexate before the protocol implementation (1 January 2009 through 31 December 2010) and 45 patients received 106 cycles of high-dose methotrexate after protocol implementation (1 January 2013 through 31 December 2014). Patient characteristics, protocol data, and complications were analyzed. Results Protocol implementation significantly reduced the deviation of methotrexate level timing at 24, 48, and 72 h: median 7.47 vs. 1.46 h, 7.23 vs. 1.35 h, and 7.00 vs. 1.52 h before and after implementation, respectively (p < 0.0001 for each). The protocol significantly reduced deviation of the first dose of leucovorin administration: median 5.2 vs. 0.675 h before and after implementation, respectively (p<0.0001). After protocol implementation, there was an increase in the use of leucovorin prescriptions written appropriately for patients discharged before methotrexate levels reached a value of ≤0.05 µmol/L. Conclusions Implementation of a protocol for the administration of high-dose methotrexate improved the adherence to consensus recommendations. Further analysis is needed to assess clinical pharmacist involvement and the cost savings implications within this protocol.

scholarly journals Evaluation of an oral sodium bicarbonate protocol for high-dose methotrexate urine alkalinization

2021 ◽  
Author(s):  
Rachel D. Heisler ◽  
Jordan J. Kelly ◽  
Sara Abedinzadegan Abdi ◽  
Jennifer L. Hawker ◽  
Leanne G. Fong ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Urine Alkalinization ◽  
Oral Sodium

Experience with ambulatory high-dose methotrexate administration as CNS prophylaxis in patients with non-Hodgkin lymphoma

2019 ◽  
Vol 26 (3) ◽  
pp. 549-555 ◽  
Author(s):  
Rubén Pampín ◽  
Yoar Labeaga ◽  
Belén Rodríguez ◽  
Beatriz Fernández ◽  
Rubén Fernández ◽  
...  
Keyword(s):  
Standard Dose ◽  
Treatment Protocol ◽  
Tertiary Hospital ◽  
High Dose ◽  
Outpatient Basis ◽  
High Dose Methotrexate ◽  
Urine Ph ◽  
Oral Hydration ◽  
Cns Prophylaxis ◽  
Dose Methotrexate

BackgroundWe describe the feasibility and safety of an oral administration schedule of hydration, alkalinization and leucovorin rescue with an ambulatory high-dose methotrexate regimen.MethodsSingle-centre prospective observational study conducted within a tertiary hospital where all patients have received systemic high-dose methotrexate (3.5 g/m2). Patients were instructed to keep an adequate ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment protocol. High-dose methotrexate was infused over 4 h. Urine pH was checked before high-dose methotrexate administration, and for any value less than 7 a sodium bicarbonate bolus was given. Leucovorin at a standard dose was begun 24 h after high-dose methotrexate. methotrexate serum concentrations were monitored daily from 24 h after administration until clearance (level ≤ 0.1 µmol/L).ResultsFrom January 2016 to June 2018, 49 ambulatory high-dose methotrexate courses were given to 18 patients. No dose reduction was required afterwards. All patients completed succesfully the planned three doses in an outpatient basis, except four patients, one of them due to pneumonitis. Previous to methotrexate infusion, urinary pH > 7 was achieved in 35 (79.5%) cycles. Methotrexate clearance was achieved by 72 h in 35 courses (71.4%), and by 96 h in 100%. Neutropenia/trombocytopenia grades III/IV were observed in four cycles (8.16%) and two (4.08%) cycles, respectively. Around 20.40% were associated with stomatitis, 14.20% vomiting, 10.20% asthenia, 8.16% diarrhea and 6.12% with renal toxicity.ConclusionsAmbulatory administration of high-dose methotrexate as CNS prophylaxis is safe and feasible following the described approach, allowing us to optimize healthcare resources.

Comparison of enteral and parenteral methods of urine alkalinization in patients receiving high-dose methotrexate

2016 ◽  
Vol 23 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Jamie A Rouch ◽  
Bradley Burton ◽  
Alix Dabb ◽  
Vicky Brown ◽  
Amy H Seung ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Sodium Citrate ◽  
Primary Objective ◽  
High Dose ◽  
Renal Tubules ◽  
Citric Acid Solution ◽  
Urine Ph ◽  
Routes Of Administration ◽  
Dose Methotrexate ◽  
Urine Alkalinization

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.

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