Medication therapy of high‐dose methotrexate: An evidence‐based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

Abstract

The authors confirm that the PI for this paper is Rongsheng Zhao and that he had direct clinical responsibility for patients included in the study investigating the patients' willingness on individualized medication of high-dose methotrexate.

Leucovorin (folinic acid) rescue for high‐dose methotrexate: A review

“…For ALL, measurements of MTX plasma concentrations and planned leucovorin rescue (15-50 mg/m 2 every 6 h) were usually performed at 36-54 h after the start of MTX infusion (the MTX doses ranged from 2.85 to 8 g/m 2 ). 9,13,20,[26][27][28][29][30][31] For lymphoma, the measurements of MTX plasma concentrations and planned leucovorin rescue (15-25 mg/m 2 or 30-100 mg every 6 h) were usually performed at 18-48 h after the start of MTX infusion (the MTX doses ranged from 2 to 8 g/m 2 ). [32][33][34] For osteosarcoma, the measurements of MTX plasma concentrations and planned leucovorin rescue (15 mg/m 2 or 10-12 mg every 6 h) were usually performed at 6-24 h after the start of MTX infusion (the MTX doses ranged from 10 to 12 g/m 2 ).…”

“…8 Therefore, hydration, alkalinization in combination with MTX monitoring, and leucovorin rescue are routine strategies to overcome MTX-induced toxicities. 9 In clinical practice, alkalinization is typically achieved with intravenous and/or oral sodium bicarbonate, sodium acetate, or acetazolamide, and the urine pH is suggested to be maintained at 7.0 or greater before and during HDMTX therapy.…”

“…Excessive alkalinization increases the risk of an acid-base disturbance. 1,9,10 However, by using these strategies, nephrotoxicity still occurs in 2%-10% of patients. 8 Therefore, MTX plasma level-guided leucovorin rescue is used to overcome HDMTX-induced toxicities.…”

“…14 Both glucarpidase and leucovorin are recommended for the treatment of MTX-induced toxicities. 9 Glucarpidase (carboxypeptidase G2) can hydrolyse circulating MTX into its inactive form deoxyaminopteroic acid and reduce plasma MTX levels by >95% within 15 min of administration. 15 Additionally, glucarpidase cannot hydrolyse intracellular MTX; therefore, leucovorin rescue is still required after glucarpidase interventions.…”

Recommendations for Off-Label Drug Use in Ophthalmology in China: A Clinical Practice Guideline

“…Furthermore, the strength of the recommendations was graded using the GRADE approach ( Guyatt et al, 2008a ; Guyatt et al, 2008b ). For each clinical question, the SR group developed finding summaries and GRADE evidence profiles to clearly describe the benefits and harms ( Song et al, 2021 ). The certainty of the body of evidence was graded as high, moderate, low, or very low.…”