Leucovorin is indicated to neutralize and diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate. Leucovorin administration should be initiated as promptly as possible. A dose of leucovorin equal to or higher than the recommended dose of methotrexate should be administered by an intravenous bolus injection within one hour. As the time interval between methotrexate administration and leucovorin initiation increases, the effectiveness of leucovorin in counteracting toxicity decreases. Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. In cases of massive overdosage, hydration and urinary alkalinization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules. Neither hemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. However, patients should be observed cautiously and other supporting measures such as a blood transfusion, renal dialysis and reverse barrier nursing may be required.
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