From the Guidelines
When leucovorin is unavailable for managing potential methotrexate toxicity with unknown dosing information, immediate administration of carboxypeptidase G2 is recommended as the primary intervention, as it can treat accidental overdoses of MTX 1. This approach is based on the understanding that carboxypeptidase G2 can effectively counteract methotrexate toxicity.
- Key considerations in managing potential methotrexate toxicity include:
- Aggressive intravenous hydration to enhance methotrexate excretion
- Close monitoring of renal function, as methotrexate can cause nephrotoxicity
- Consideration of alternative folate rescue options, although carboxypeptidase G2 is the preferred choice when leucovorin is unavailable
- Laboratory monitoring should include:
- Daily methotrexate levels to assess the effectiveness of the intervention
- Complete blood counts to detect potential myelosuppression
- Liver function tests to monitor for hepatotoxicity
- Renal function tests to assess for nephrotoxicity
- Patients should be closely monitored for signs of toxicity, including mucositis, myelosuppression, hepatotoxicity, and nephrotoxicity, and managed accordingly 1.
From the FDA Drug Label
Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion In the presence of gastrointestinal toxicity, nausea, or vomiting, leucovorin should be administered parenterally. Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. If glucarpidase is used, do not administer leucovorin within two hours before or after a dose of glucarpidase because leucovorin is a substrate for glucarpidase. The management for potential methotrexate (MTX) toxicity when leucovorin is unavailable and methotrexate dosing information is unknown involves:
- Hydration: Administering hydration (3 L/d) to help eliminate methotrexate from the body 2
- Urinary alkalinization: Using sodium bicarbonate to maintain a urine pH of 7 or greater, which can help reduce the precipitation of methotrexate in the renal tubules 2
- Consideration of alternative treatments: If available, glucarpidase may be considered for the treatment of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function 3 Note: The above management is based on the information available and may not be comprehensive or entirely effective in the absence of leucovorin and methotrexate dosing information.
From the Research
Management of Methotrexate Toxicity
When leucovorin is unavailable and methotrexate dosing information is unknown, the management of potential methotrexate (MTX) toxicity becomes challenging. The following options can be considered:
- Charcoal Hemoperfusion: Charcoal hemoperfusion (CHP) can be used as a rescue treatment option in MTX intoxication, as it is an effective and safe extracorporeal method for removing MTX 4.
- Thymidine: Thymidine can be used in combination with leucovorin to treat MTX toxicity, as it has been shown to be effective in preventing severe toxicity 5, 6.
- Supportive Care: Supportive care, including hydration and sodium bicarbonate administration, can help to manage MTX toxicity 7, 6.
- Monitoring: Rigorous monitoring of serum creatinine and serum MTX levels 24-48 hours after MTX administration can help to identify patients at risk of MTX-induced renal failure and allow for the institution of rescue measures 6.
Considerations
- Leucovorin Dosing: The optimum dose of leucovorin for treating MTX toxicity is unclear, and studies have shown that different doses may be effective 8.
- MTX Levels: MTX levels can remain elevated for several days after administration, and monitoring of these levels can help to guide treatment 7, 5.
- Renal Function: MTX can cause a decrease in glomerular filtration rate, even in non-toxic courses, and monitoring of renal function is important in patients receiving MTX 6.