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Assessing the impact of adding acetazolamide to oral or intravenous sodium bicarbonate as compared with intravenous bicarbonate monotherapy as urinary alkalinization in adults receiving high-dose methotrexate

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Abstract

Purpose

High-dose methotrexate (HD-MTX) requires urine alkalinization to pH ≥ 7 for adequate excretion to prevent toxicity. Due to shortages of IV sodium bicarbonate (IV-NaHCO3), few reports have demonstrated utility of oral bicarbonate (PO-NaHCO3); however, the addition of acetazolamide (Acet) has not been well described. Our study compares outcomes between alkalinization methods of IV-NaHCO3 monotherapy versus IV-NaHCO2 + Acet and PO-NaHCO3 + Acet.

Methods

A single-center, IRB exempt, retrospective review was conducted from Jan 2016 to Sept 2019 of adults receiving HD-MTX ≥ 500 mg/m2. The primary outcome was time from start of alkalinization to pH ≥ 7. Secondary outcomes included time from start of alkalinization to initiation of HD-MTX, time to MTX clearance, length of stay (LOS), percentage of urine pH assessments < 7, and incidence of MTX toxicity. Statistical analysis was performed using SAS9.4 with alpha 0.05.

Results

Overall demographics (n = 196 HD-MTX cycles for 55 patients) include a mean age 55 years, HD-MTX dose ~ 5400 mg/m2, and 69% with a diagnosis of lymphoma. Adjusting for baseline demographic differences among groups, median time from first dose alkalinization to pH ≥ 7 and to start of HD-MTX was longer for those receiving IV-NaHCO3 (n = 41) vs either IV-NaHCO3 + Acet (n = 70) or PO-NaHCO3 + Acet (n = 76) (p = 0.0001). HD-MTX clearance to a level < 0.1 μmol/L was not improved with the addition of Acet. No difference existed among groups for pH results < 7, LOS, or incidence of MTX toxicity (p > 0.05).

Conclusions

Addition of Acet to NaHCO3 reduces time to pH ≥ 7 and initiation of HD-MTX but does not appear to improve LOS, MTX toxicities, or time to MTX clearance.

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Acknowledgments

The use of REDCap was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. University of Georgia College of Pharmacy, Augusta, GA, USA

    Amber B. Clemmons, Aaron Chase & Phung Duong

  2. Department of Pharmacy, Augusta University Medical Center, 1120 15th Street, HM 104, Augusta, GA, 30912, USA

    Amber B. Clemmons & Katherine Saunders

  3. Georgia Cancer Center, Augusta, GA, USA

    Amber B. Clemmons & Katherine Saunders

  4. Department of Population Health Sciences, Division of Biostatistics and Data Science, Augusta University, Augusta, GA, USA

    Jennifer L. Waller

  5. Department of Medicine, Augusta University Medical Center, Augusta, GA, USA

    Locke Bryan

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  1. Amber B. Clemmons
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  2. Aaron Chase
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Correspondence to Amber B. Clemmons.

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This study was not funded by any entity.

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Clemmons, A.B., Chase, A., Duong, P. et al. Assessing the impact of adding acetazolamide to oral or intravenous sodium bicarbonate as compared with intravenous bicarbonate monotherapy as urinary alkalinization in adults receiving high-dose methotrexate. Support Care Cancer 29, 1527–1534 (2021). https://doi.org/10.1007/s00520-020-05646-z

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  • DOI: https://doi.org/10.1007/s00520-020-05646-z

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