皮膚科 劉權毅醫師

Daily supplementation with 1 to 5 mg of folate has reduced nausea, vomiting, stomatitis and oral ulceration, elevated transaminases, and mild myelosuppression without compromising the efficacy of methotrexate.8-11 Liver fibrosis, pneumonitis, and moderate to severe myelosuppression are not mitigated by folate supplementation. Elevated homocysteine levels, common with methotrexate use and an independent risk factor for coronary artery disease, are decreased with folate supplementation.32
Folinic acid should not be given on the same days as methotrexate dosing. Unlike folinic acid, folate does not compete with methotrexate for cellular uptake. Folate is also considerably cheaper than folinic acid. For these reasons, folate supplementation is preferred by many authorities. One drawback to folate supplementation is the potential masking of vitamin B12 deficiency. Use of folate supplementation with methotrexate therapy is increasing rapidly. Methotrexate overdose is more likely in patients with declining renal function, in those who misunderstand dosing directions, or in those concomitantly exposed to a second folate antagonist, such as trimethoprim-sulfamethoxazole. Overdose should be treated promptly with folinic acid (leucovorin). Folinic acid is metabolized in vivo to tetrahydrofolate in the absence of dihydrofolate reductase, providing an alternative supply of DNA and RNA precursors. Folinic acid should be given early, preferably within the first 24 to 36 hours after overdose. Folinic acid itself has very little toxicity. Therefore, an oral dose of 10 mg/m2 should be given on first suspicion of methotrexate overdose without delay for a serum assay. Peroral or parenteral doses may be continued every 6 hours until the serum concentration of methotrexate falls to less than 10-8 M.7 Practically speaking, or when a serum assay is unavailable, this recommendation is often equivalent to 15 to 25 mg of folinic acid by mouth every 6 hours for 6 to 10 doses.

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