What is the leucovorin (folinic acid) dosage for methotrexate toxicity in a patient with psoriasis?

From the Guidelines

For methotrexate toxicity in a patient with psoriasis, leucovorin (folinic acid) rescue should be initiated as soon as possible at a dose of 10 mg/m² every 6 hours. This recommendation is based on the guidelines of care for the management of psoriasis and psoriatic arthritis, which suggest that folinic acid (leucovorin) is 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, emphasizing the need for prompt initiation of leucovorin rescue 1.
• Folinic acid should be given immediately, with subsequent doses given every 6 hours, to effectively bypass the metabolic block caused by methotrexate and provide reduced folate for DNA synthesis and repair.
• The dose of 10 mg/m² every 6 hours is specified in the guidelines as the appropriate dosage for folinic acid rescue in cases of methotrexate toxicity 1.

Additional Measures

• Supportive care measures, such as aggressive hydration with alkalinization of urine, discontinuation of methotrexate, and avoidance of medications that may increase methotrexate toxicity, should also be implemented to manage methotrexate toxicity.
• Close monitoring of blood counts, liver function tests, and serum urea nitrogen and creatinine levels is essential to promptly identify and address any potential toxic effects of methotrexate 1.

From the FDA Drug Label

Leucovorin Rescue After High-Dose Methotrexate Therapy The recommendations for leucovorin rescue are based on a methotrexate dose of 12 to 15 grams/m2 administered by intravenous infusion over 4 hours 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 CALCIUM FOR INJECTION DOSAGE AND ADMINISTRATION Clinical SituationLaboratory FindingsLeucovorin Calcium for Injection Dosage and Duration NormalMethotrexate Elimination Serum methotrexate level approximately 10 micromolar 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 micromolar at 72 hours, and more than 0. 05 micromolar at 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 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 leucovorin dosage for methotrexate toxicity is:

• 15 mg every 6 hours for 10 doses, starting 24 hours after methotrexate infusion, for normal methotrexate elimination.
• 15 mg every 6 hours, until methotrexate level is less than 0.05 micromolar, for delayed late methotrexate elimination.
• 150 mg IV every 3 hours, until methotrexate level is less than 1 micromolar, then 15 mg IV every 3 hours, until methotrexate level is less than 0.05 micromolar, for delayed early methotrexate elimination and/or evidence of acute renal injury. 2

From the Research

Leucovorin (Folinic Acid) Dosage for Methotrexate Toxicity

• The provided studies do not specify the exact leucovorin (folinic acid) dosage for methotrexate toxicity in patients with psoriasis 3, 4, 5, 6, 7.
• However, it is mentioned that folinic acid was used to treat methotrexate toxicity in several cases 5, 6.
• In one study, all cases of methotrexate toxicity were treated with folinic acid, and 85% of patients recovered within 7-14 days 5.
• Another study reported that all cases of toxicity due to overdosing of methotrexate were given injectable folinic acid, and five cases recovered while two cases expired 6.

Causes and Risk Factors of Methotrexate Toxicity

• Overdosing is a major cause of acute methotrexate toxicity in psoriasis patients 5, 6.
• Inadvertent daily dosing instead of weekly dosing can lead to toxicity 3, 4, 7.
• Concomitant factors such as older age, co-medication, and renal failure may increase the risk of methotrexate toxicity 3, 4.
• Lack of counseling regarding the disease course, drug dosing, schedule, and awareness about possible outcomes of high and daily doses can contribute to overdosing and toxicity 6.