The pharmacokinetics of methotrexate are highly variable and unpredictable. Methotrexate; Acute renal failure; Leukoencephalopathy Summary High-dose methotrexate (HDMTX) is an important component in the treatment of a variety of solid tumors and hematological malignancies.
No clear dose instruction was captured by data extraction for 29 of these patients on oral medication, leaving 214 whose dose could be viewed relative to an eGFR result.Hence 121 (5.7%) of 2,110 patients received a dose greater than 12.5mg per week.Following advice and guidance issued to primary care, a repeat database extraction for the three months to end-March 2019 identified 2,322 patients on weekly methotrexate with 3.6% (84/2322) prescribed a dose too high for their eGFR value.There is a need to review patients receiving methotrexate in relation to their renal function. Atypon When renal function is reduced, accumulation may lead to toxicity such as excessive bone marrow suppression, acute hepatic toxicity, and acute interstitial pneumonitis.
Therefore, the combination of a lower plasma methotrexate level and the transient presence of glucarpidase probably enhances the intracellular transport of leucovorin.Many curable cancers require multiple courses of HDMTX therapy. Methotrexate may cause renal damage that may lead to acute renal failure. Concomitantly, daily ChH resulted in a median decrease in serum MTX level of 41% (range, 28–65%).In conclusion, the incidence of HDMTX-induced severe ARF in adults with haematological malignancies may be considerably higher than that observed in other cancer patients.
Their creatinine clearance decreased an average of 61%.
Findings in post‐methotrexate liver biopsies from 160 psoriatics2004 annual report of the American Association of Poison Control Centers toxic exposure surveillance systemMethotrexate for rheumatoid arthritis.
Methotrexate formulations or diluents containing preservatives should not be used for intrathecal or high-dose therapy.
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For instance, HDMTX doses can be reduced in patients with pre‐existing renal dysfunction or severe toxicity after a prior course of HDMTX, and serum methotrexate levels can be measured early (e.g., at hour 6 of a 24‐hour infusion) to make sure that there is no excessive accumulation [The pharmacokinetics of methotrexate dictate the degree of supportive care and monitoring needed after treatment.
School of Health Studies, University of Memphis, Memphis, Tennessee, USADepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, New York, New York, USADepartment of Oncology, St. Jude Children's Research Hospital, New York, New York, USASchool of Health Studies, University of Memphis, Memphis, Tennessee, USADepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USASchool of Health Studies, University of Memphis, Memphis, Tennessee, USADepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, New York, New York, USADepartment of Oncology, St. Jude Children's Research Hospital, New York, New York, USASchool of Health Studies, University of Memphis, Memphis, Tennessee, USADepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USADisclosures of potential conflicts of interest may be found at the end of this article.Use the link below to share a full-text version of this article with your friends and colleagues. Search for other works by this author on: The diagnosis was based on markedly elevated serum MTX levels (>10 μmol/L at 48 h after HDMTX) and severe ARF (grade 3–4 increases in serum creatinine, according to WHO criteria). Plasma protein binding, effusions, renal function, and, to a lesser degree, hepatic function can all contribute to peak concentrations after infusion.
Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of therapy. Search for other works by this author on:
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