Sunday, February 01, 2015

Methotrexate overdose

From the Journal of Toxicology:

Objective. Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000–2005) which exceed 180,000 exposures/year.. No patient in the series received dialysis or died. The mean dose ingested for all patients was 24mg (range 2.5–100mg) and the mean dose for suicidal ingestions was 47.5mg (12.5–100mg). The most common clinical effects were abdominal pain, oral irritation, throat irritation, nausea, dizziness, and headache. Nine patients received folinic acid and 3 patients received sodium bicarbonate. No patient developed renal failure, bone marrow suppression, seizure, or coma. No patient died or received dialysis. Conclusion. In our series of patients from 6 poison centers over six years, 63 cases of acute adult methotrexate ingestions were reported. Methotrexate toxicity from ingestion in adults was uncommon and rarely toxic...

Methotrexate has been used in parenteral form as a chemotherapeutic agent for decades. In recent years, the oral form has been used for the treatment of rheumatologic conditions with both increased frequency and dosage [8]. Parenteral methotrexate toxicity has been examined, and several effects such as renal failure, respiratory failure, myelosuppression, and neurologic disruption have been described [1, 9]. Recent case reports have described fatal overdose of methotrexate ingestions, although no data from a large series of acute ingestions has been reviewed until now [4].

While several antidotes have been postulated for methotrexate toxicity, folinic acid (leucovorin) has been shown to be the most effective and has few known complications [10]. We found that the use of methotrexate-specific treatments was uncommon, possibly suggesting that physicians were unfamiliar with this rarely used drug or the physicians were not concerned the patients were ill and need it...

Based on these findings, supportive care and observational therapy without methotrexate-specific treatment should be considered in acute ingestions. Patients can be monitored for development of renal insufficiency, neurologic effects, or bone marrow suppression. Based on the clinical effects and followup, the measurements and reexaminations could be done as an inpatient or outpatient. A large, prospective study to evaluate this treatment approach is warranted.

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