Trexan Overdosage

Cases of overdose, sometimes fatal, due to erroneous daily intake instead of weekly intake of oral methotrexate have been reported. In these cases, symptoms that have been commonly reported are haematological and gastrointestinal reactions.
The toxicity of methotrexate affects mainly the haematopoietic organs. Calcium folinate neutralises effectively the immediate toxic effects of methotrexate. Parenteral calcium folinate therapy should be started within one hour after the administration of methotrexate. The dose of calcium folinate should be at least as high as the dose of methotrexate received by the patient.
Symptoms of an overdose are mainly the same as the undesirable effects, but stronger.
Leucovorin is a specific antidote for methotrexate and, following accidental overdosage, should be administered within one hour at a dosage equal to, or greater than, the methotrexate dose. It may be administered by i.v. bolus or infusion. Further doses may be required. The patient should be observed carefully and blood transfusions, renal dialysis and reverse barrier nursing may be necessary.
In post-marketing experience, overdose with methotrexate has generally occurred with oral and intrathecal administration, although intravenous and intramuscular overdose has also been reported.
Cases of overdose have been reported, sometimes fatal, due to erroneous daily intake instead of weekly intake of oral methotrexate. In these cases, symptoms that have been commonly reported are hematological 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 anaemia were also reported.
In cases of massive overdose, hydration and urinary alkalisation may be necessary to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Neither haemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. Effective clearance of methotrexate has been reported with acute, intermittent haemodialysis using a high flux dialysator. Observation of serum methotrexate concentrations is relevant in determining the right dose of calcium folinate and the duration of the therapy. Treatment measures for methotrexate overdosage can be discontinued when the serum methotrexate level has fallen below the level of 5x10^-8 M (10) (see Precautions).