From the Guidelines
For methotrexate toxicity, leucovorin (folinic acid) should be administered at a dose of 10 mg/m² every 6 hours until methotrexate levels are no longer toxic. This dose is based on the guidelines for the management of psoriasis and psoriatic arthritis, which recommend folinic acid (at 10 mg/m²) as the antidote for the hematologic toxic effects of methotrexate 1.
Key Considerations
- The effectiveness of folinic acid in counteracting the hematologic toxicity of methotrexate decreases as the time interval between methotrexate administration and folinic acid treatment increases, so folinic acid should be given immediately with subsequent doses given every 6 hours 1.
- The route of administration depends on severity, with oral administration suitable for mild toxicity and intravenous administration preferred for moderate to severe toxicity or if the patient cannot tolerate oral medication.
- Supportive care including hydration, urinary alkalinization, and monitoring of renal function and blood counts should accompany leucovorin rescue therapy.
Important Details
- Leucovorin works by providing reduced folate that bypasses the methotrexate-induced blockade of dihydrofolate reductase, allowing for continued DNA synthesis in healthy cells.
- Higher doses of leucovorin may be required for severe toxicity or significantly elevated methotrexate levels, but the initial dose recommended is 10 mg/m² every 6 hours 1.
- It is essential to monitor blood counts and adjust the dose of leucovorin accordingly to prevent further toxicity.
From the FDA Drug Label
Leucovorin 15 mg (10 mg/m2) should be administered IM, IV, or PO every 6 hours until the serum methotrexate level is less than 10-8 M If the 24-hour serum creatinine has increased 50% over baseline or if the 24-hour methotrexate level is greater than 5 x 10-6 M or the 48-hour level is greater than 9 x 10-7 M, the dose of leucovorin should be increased to 150 mg (100 mg/m2) IV every 3 hours until the methotrexate level is less than 10-8 M.
The recommended dose of leucovorin for methotrexate (MTX) toxicity is 15 mg (10 mg/m2) every 6 hours, which can be administered IM, IV, or PO. However, if certain conditions are met, such as increased serum creatinine or high methotrexate levels, the dose should be increased to 150 mg (100 mg/m2) IV every 3 hours 2.
From the Research
Leucovorin Dose for MTX Toxicity
The recommended dose of leucovorin (folinic acid) for methotrexate (MTX) toxicity varies depending on the severity and type of toxicity.
- For severe low-dose methotrexate toxicity, a dose of 15 mg every 6 hours is commonly used 3.
- For high-dose MTX toxicities, early intravenous folinic acid administration is recommended, with dose and duration being guided by MTX concentrations and clinical improvement 4.
- In some cases, a higher dose of leucovorin (25 mg every 6 hours) may be used, but there is no significant difference in survival or time-to hematological recovery between the two doses 3.
- Additional doses of leucovorin (15 mg/m2/dose) can be administered every 6 hours, with extended hydration and monitoring of serum creatinine and urine pH 5.
Factors Influencing Leucovorin Dose
The dose of leucovorin required to treat MTX toxicity can be influenced by several factors, including:
- The dose and frequency of MTX administration
- The severity of toxicity
- Renal function
- The presence of other medical conditions
Administration of Leucovorin
Leucovorin can be administered intravenously or orally, depending on the severity of toxicity and the patient's condition.