In post-marketing experience, overdose with methotrexate has generally occurred with oral administration.
Reports of oral overdose indicate accidental daily administration instead of weekly (single or divided doses). Symptoms commonly reported following oral overdose include those symptoms and signs reported at pharmacologic doses, particularly hematologic and gastrointestinal reactions. For example, leukopenia, thrombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, gastrointestinal bleeding. In some cases, no symptoms were reported. There have been reports of death following chronic overdose in the self administered dosage for rheumatoid arthritis and psoriasis (see Dosage & Administration and Precautions). In these cases, events, such as sepsis or septic shock, renal failure, and aplastic anemia were also reported.
Recommended treatment: Folinic acid is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdoses of methotrexate. Folinic acid administration should begin as promptly as possible. As the time interval between methotrexate administration and leucovorin initiation increases, the effectiveness of folinic acid in counteracting toxicity decreases. Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with folinic acid.
In cases of massive overdose, hydration and urinary alkalization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules. Neither standard hemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. However, effective clearance of methotrexate has been reported with acute, intermittent hemodialysis using a high-flux dialyzer.