Sodium acetate a safe, efficacious option for alkalinization in patients on high-dose MTX

Intravenous (IV) sodium acetate is as efficacious and safe as IV sodium bicarbonate for urine alkalinization with high-dose methotrexate (MTX) and may be used as a substitute in case of shortage, suggests a retrospective study.

“In the event of a future IV sodium bicarbonate shortage, this single-centre experience supports the consideration of IV sodium acetate as an alternative alkalinizing agent for patients undergoing treatment with high-dose MTX,” the researchers said.

Adults admitted to Barnes-Jewish Hospital in Missouri, US, to receive high-dose MTX for lymphoma, breast cancer with leptomeningeal spread, or osteosarcoma were included in this retrospective cohort study. Those who had received IV sodium acetate or sodium bicarbonate alkalinization were eligible.

A total of 192 encounters with high-dose MTX were included in the analysis, of which 154 (sodium bicarbonate, n=86; sodium acetate, n=68) were assessed for safety and efficacy. [J Oncol Pharm Pract 2023;doi:10.1177/10781552211060287]

No significant between-group difference was observed in safety outcomes, except for higher peak MTX level (2.9 vs 1.7 mcmol/L; p=0.023) and increased incidence of grade 3‒4 alanine aminotransferase in the bicarbonate group (23.5 percent vs 9 percent; p=0.02).

In addition, time from alkalinizer initiation to pH ≥7, the primary endpoint, was markedly shorter in the bicarbonate group (4 vs 5.15 h; p=0.021). However, sodium acetate was associated with shorter inpatient time for outcomes such as length of stay (LOS; 4.4 vs 4 days; p=0.037) and time to MTX clearance (3.6 vs 3.2 days; p=0.023) overall.

“Although the primary endpoint … was statistically significant in favour of IV sodium bicarbonate, the difference of <1.5 h was not of clinical significance,” the researchers said. “This result was contradicted with results of other endpoints favouring IV sodium acetate, such as LOS and time to clear MTX, the difference for both outcomes approximately 9–10 h between groups.”

In another retrospective study, investigators at Children’s Hospital of Colorado, US, evaluated the use of IV sodium acetate, oral sodium citrate, and oral sodium bicarbonate for urine alkalinization in paediatric patients receiving high-dose MTX. [J Pediatr Hematol Oncol 2019;41:371-375]

Oral options were initiated first due to a shortage in sodium acetate at the time of the study. Patients who switched from oral agents to IV sodium acetate before achieving the pH goal (n=26, 25.5 percent of cycles) were excluded from the analysis. Intolerance (10/26) and inadequate alkalinization (11/26) were the most common reasons for the switch.

“Conclusions could not be drawn regarding IV sodium acetate use as it was a second line option and was limited in supply,” the investigators said. “Additionally, this study evaluated the paediatric population, limiting generalizability of conclusions to adult patients.”

Of note, while IV sodium acetate may serve as an effective option, it remains not immune to shortages.

“Further prospective studies are needed to establish IV sodium acetate as a routine alternative choice in the absence of an IV sodium bicarbonate shortage,” the researchers said.