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Pharmacotherapy with high doses of methotrexate (HDMTX) in oncology – how should chemotherapy be conducted based on therapeutic drug monitoring?
Aleksandra Mikulska
Arkadiusz Kocur
Abstract
Methotrexate (MTX) is a crucial cytostatic drug used both in autoimmune diseases (low doses) and cancer chemotherapy, especially in the lymphatic system (high doses). MTX is a folic acid antagonist with a strong affinity for enzymes involved in the folic pathway. It is a highly toxic drug with documented prevention of side effects using compensatory therapy with leucovorin. High-dose methotrexate (HDMTX) is administered as an intravenous bolus with a body surface area of > 500 mg/m2. Because these concentrations are highly toxic, but at the same time, the therapeutic benefits are higher than the compensated side effects, it is necessary to conduct therapeutic drug monitoring. During pharmacotherapy with MTX, routine monitoring of MTX and serum creatinine concentrations is performed, while the dose of leucovorin infusion, with the possible addition of glucarpidase, is adjusted simultaneously.
The aim of this study was a mini-review of the pharmacological properties of MTX, combined with a particular emphasis on the variability in the pharmacokinetics of this drug, justifying the need for therapeutic monitoring of concentrations. HDMTX therapy, clinical recommendations, and therapy methods based on global guidelines are discussed. In addition, the issues of both MTX treatment and salvage treatment with leucovorin and glucarpidase were discussed.
HDMTX treatment should be performed under special supervision following the accepted clinical protocol. Only the appropriate cooperation of the doctor, nursing staff, laboratory diagnosticians, clinical pharmacists, and, most importantly, the patient should allow for effective treatment, with the appropriate reduction of toxic side effects to a minimum.
Keywords:
methotrexate, pharmacokinetics, HDMTX, therapeutic drug monitoring, toxicity, leucovorinMost read articles by the same author(s)
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