From the FDA Drug Label
Leucovorin rescue at a dose of 15 mg (approximately 10 mg/m2) every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion.
GUIDELINES FOR LEUCOVORIN DOSAGE AND ADMINISTRATION Clinical Situation Laboratory Findings Leucovorin Dosage and Duration Normal Methotrexate Elimination Serum methotrexate level approximately 10 micromo-molar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours. 15 mg PO, IM, or IV q 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion). Delayed Late Methotrexate Elimination Serum methotrexate level remaining above 0.2 micrommolar at 72 hours, and more than 0. 05 micromolar 96 hours after administration. Continue 15 mg PO, IM, or IV q 6 hours, until methotrexate level is less than 0. 05 micromolar. Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0. 5 mg/dL to a level of 1 mg/dL or more). 150 mg IV q 3 hours, until methotrexate level is less than 1 micromolar; then 15 mg IV q 3 hours until methotrexate level is less than 0. 05 micromolar.
The duration of leucovorin administration in a patient with psoriasis experiencing methotrexate toxicity is as follows:
- Normal Methotrexate Elimination: 60 hours (10 doses starting at 24 hours after start of methotrexate infusion) 1
- Delayed Late Methotrexate Elimination: Continue until methotrexate level is less than 0.05 micromolar 1
- Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury: Until methotrexate level is less than 0.05 micromolar 1
From the Research
Leucovorin should be administered until methotrexate levels fall below 0.05-0.1 μmol/L, typically requiring 24-72 hours of therapy in cases of methotrexate toxicity in psoriasis patients, as supported by the most recent study 2. The standard rescue protocol involves 15 mg of leucovorin (folinic acid) administered orally or intravenously every 6 hours until methotrexate levels are sufficiently reduced. Some key points to consider in the management of methotrexate toxicity include:
- Monitoring of complete blood counts, renal function, and liver enzymes should accompany leucovorin administration, as highlighted in various studies 3, 4, 5.
- Hydration and urinary alkalinization are important adjunctive measures to enhance methotrexate clearance and reduce toxicity risk.
- For severe toxicity, higher doses of 100-1000 mg/m² may be required, with dosing adjusted based on methotrexate serum levels and clinical symptoms.
- Leucovorin works by bypassing the metabolic block caused by methotrexate, providing reduced folates necessary for DNA synthesis and cellular function, thus preventing prolonged folate antagonism that leads to toxicity in rapidly dividing cells like bone marrow and gastrointestinal mucosa.
- A recent multicentric retrospective study 2 found that overdosing was the most common cause of drug toxicity, either inadvertent or due to self-medication, emphasizing the need for patient counseling regarding the course of the disease, drug regimen, and potential side effects.
- The same study 2 reported that 85% of patients recovered within 7-14 days with folinic acid treatment, highlighting the importance of prompt medical intervention in cases of methotrexate toxicity.