Do intravenous fluid substitutions influence methotrexate clearance? An unanticipated impact of an intravenous sodium bicarbonate drug shortage.

Abstract

BACKGROUND:

National drug shortages of essential medications for childhood cancer have increasingly posed a challenge in the treatment of patients. The efficacy of standardized supportive care practices to avoid treatment-related toxicities may be limited during these drug shortages. High-dose methotrexate (HDMTX) plays a critical role in modern treatment protocols for acute lymphoblastic leukemia and requires stringent supportive care measures to mitigate toxicity. As the result of a national intravenous (IV) sodium bicarbonate shortage, institutional standard HDMTX supportive care guidelines had to be modified. We describe the unanticipated consequences on HDMTX clearance.

METHODS:

We performed a retrospective chart review assessing the impact of alternative compositions of IV fluids on the mean 24-h methotrexate levels (Cpss ) of 25 patients receiving 76 total HDMTX infusions at Texas Children's Hospital Cancer Center from March to October 2017. During the sodium bicarbonate drug shortage, all patients received IV hydration consisting of either dextrose 5%, 0.45% normal saline (D5 ½ NS-Group A) or dextrose 5%, 0.2% normal saline (D5 ¼ NS-Group B).

RESULTS:

Patients receiving a higher total sodium dose demonstrated significantly lower Cpss (25.36 ± 16.6 μMol) compared to patients receiving less sodium (53.9 ± 37.9 μMol; P < .001).

CONCLUSIONS:

Our report shows that in the setting of IV sodium bicarbonate shortage, the composition of hydration IV fluids may affect methotrexate clearance. Patient who received a higher sodium load had a lower 24-h methotrexate level. This demonstrates the potential for unanticipated outcomes resulting from national drug shortages.

• Authors: Ross Mangum, M Brooke Bernhardt, W Susan Cheng, Eric S Schafer, Stacey L Berg, Jennifer H Foster
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 67 Issue 9 Pg. e28334 (09 2020) ISSN: 1545-5017 [Electronic] United States
• PMID: 32608575 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Antimetabolites, Antineoplastic
• Sodium Bicarbonate
• Sodium
• Methotrexate

Topics

• Administration, Intravenous
• Adolescent
• Antimetabolites, Antineoplastic (adverse effects, pharmacokinetics, therapeutic use)
• Child
• Child, Preschool
• Female
• Humans
• Male
• Methotrexate (adverse effects, pharmacokinetics, therapeutic use)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Retrospective Studies
• Sodium (administration & dosage)
• Sodium Bicarbonate (administration & dosage, therapeutic use)