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 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

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.

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).

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.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate

2017 ◽  
Vol 37 (6) ◽  
pp. 684-691 ◽  
Author(s):  
Sarah A. Drost ◽  
Jason R. Wentzell ◽  
Pierre Giguère ◽  
Darcy L. McLurg ◽  
Mitchell Sabloff ◽  
...  
Keyword(s):  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Urine Alkalinization

Leucovorin (LV) pharmacokinetics in patients receiving high dose methotrexate (HDMTX), with or without glucarpidase treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20521-e20521
Author(s):  
Stefan Schwartz ◽  
Thomas King ◽  
Suzanne Ward ◽  
Angela Ogden ◽  
Nikhil Chauhan ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Kidney Injury ◽  
Primary Objective ◽  
High Dose ◽  
Plasma Samples ◽  
High Dose Methotrexate ◽  
Open Label ◽  
Carboxypeptidase G2 ◽  
Dose Methotrexate ◽  
Clinical Trial Information

e20521 Background: Glucarpidase is a recombinant form of carboxypeptidase G2 and hydrolyzes MTX into inactive metabolites and provides alternate clearance in pts with delayed elimination and acute kidney injury. It is administered with IV hydration, urinary alkalinization, and LV. The primary objective was to investigate whether glucarpidase reduces exposure to LV and its active metabolite (5EMeTHF) to below the level achieved in pts who have not received glucarpidase, by assessing the PK of the active L-isomer of LV (6S-LV) following administration of HDMTX and LV. Methods: Open-label, multicenter PK study in pts treated with HDMTX (≥1 g/m2) and LV (either ≥15 mg or ≥10 mg/m2) with subsequent glucarpidase where indicated for renal impairment (Arm A) or without glucarpidase (Arm B). Plasma samples for LV and 5EMeTHF were taken pre-LV and at 5, 30, 60, 120, and 180 min after LV to calculate the area under the concentration curve of 6S-LV over 0-3 hours (AUC0-3) following the LV dose. Results: 17 pts (8 Arm A, 9 Arm B) were analyzed. The median pre-glucarpidase methotrexate (MTX) plasma concentration was higher for Arm A 7.5 µmol/L) than B (1.1 µmol/L). Similarly, median LV doses were 89.88 mg/m2 (Arm A) and 13.51 mg/m2(Arm B). Mean 6S-LV AUC0-3 values (µmol*h/L) for Arm A were 8.70±5.56, compared with 1.31±0.78 for Arm B, consistent with Arm A receiving a higher LV dose than Arm B. Mean 6S-5MeTHF AUC0-3 values (µmol*h/L) were similar in arms A and B (0.68 and 0.73). When normalized for LV doses, mean 6S-LV AUC0-3values (µmol*h/L) were similar between arms:10.02±4.83 in Arm A versus 9.79±5.18 for Arm B. Conclusions: Glucarpidase does not reduce exposure to 6S-LV and 5-MeTHF to below the level achieved in patients with normal renal function who did not receive glucarpidase. Adequate LV exposure is achieved if LV dosing is based on pre-glucarpidase plasma MTX concentration for at least 48 hours after glucarpidase administration. Clinical trial information: NCT00634504.

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