From the Guidelines
Treatment of methotrexate toxicity primarily involves leucovorin (folinic acid) rescue therapy, which should be initiated as soon as possible after methotrexate overdose is recognized, with oral leucovorin (10 mg) administered twice daily, beginning on the day of treatment and continuing for 3 days, to mitigate systemic toxicity 1.
Key Considerations
- Accidental overdoses of MTX can be treated with carboxypeptidase G2, which highlights the importance of having this treatment option available in cases of MTX toxicity 1.
- Leucovorin does not appear to cross the blood-brain barrier in amounts sufficient to interfere with the effect of MTX in the CSF, making it a safe choice for mitigating systemic toxicity without compromising the therapeutic effect of MTX in the central nervous system 1.
- Relative contraindications to IT MTX include renal insufficiency, large pleural effusions, ascites, and abnormal CSF flow, which are important to consider when assessing the risk of MTX toxicity 1.
Management of MTX Toxicity
- Aggressive hydration and urinary alkalinization are crucial to enhance methotrexate excretion and prevent precipitation in renal tubules, although specific details on this are not provided in the study 1.
- Supportive care includes managing specific manifestations of toxicity such as myelosuppression, mucositis, and monitoring liver and kidney function, which are critical components of comprehensive care for patients with MTX toxicity.
- The use of glucarpidase (carboxypeptidase G2) and hemodialysis or hemoperfusion may be considered in severe cases of MTX toxicity, particularly when there is renal dysfunction or when standard measures are insufficient 1.
From the FDA Drug Label
OVERDOSAGE: Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate. Leucovorin administration should begin as promptly as possible. 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 Glucarpidase is indicated for the treatment of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function
The treatment for Methotrexate (MTX) toxicity includes:
- Leucovorin administration as soon as possible to counteract the effects of methotrexate overdose
- Hydration and urinary alkalinization in cases of massive overdosage to prevent precipitation of methotrexate in the renal tubules
- Glucarpidase for patients with delayed methotrexate clearance due to impaired renal function 2
From the Research
Treatment for Methotrexate (MTX) Toxicity
The treatment for MTX toxicity has several goals, including clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment 3. The preferred antidote for MTX poisoning is folinic acid, which is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after high-dose MTX therapy 3.
Treatment Options
- Clearance of MTX from the bloodstream: This can be achieved through hydration and urinary alkalinization 4.
- Folinic acid therapy: High-dose leucovorin can be used as a sole therapy for MTX toxicity without the need for extracorporeal removal and with tolerable morbidity 5.
- Organ treatment: Treatment of organ toxicity, such as acute kidney injury (AKI), is crucial to prevent further toxicity and facilitate renal recovery 4.
- Glucarpidase: This enzyme has been licensed for the treatment of high plasma MTX levels of >1 μmol/L in patients with compromised renal function who have delayed MTX elimination 3, 6.
Prevention of Toxicity
Prevention of MTX toxicity is essential, and measures include:
- Monitoring of serum creatinine, urine output, and serum methotrexate concentration to assess renal clearance 4.
- Concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity 4.
- Avoidance of drug interactions that may increase the risk of MTX toxicity 7, 4.
- Implementation of safety-practical measures to prevent administration errors 7.