Treatment of High Dose Methotrexate Toxicity with Glucarpidase
- Corresponding Author:
- Darko Mitrovic
Department of Clinical Pharmacology and
Clinical Pharmacy, University Medical Centre
Groningen, Thialfweg 44, 8441 PW Heerenveen, The Netherlands
Tel: 0513 685 685
E-mail: [email protected]
Received date: March 18, 2016; Accepted date: April 23, 2016; Published date: April 27, 2016
Citation: Mitrovic D, Touw DJ, Tissing W (2016) Treatment of High Dose Methotrexate Toxicity with Glucarpidase . J Clin Toxicol 6:293. doi: 10.4172/2161-0495.1000293
Copyright: © 2016 Mitrovic D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
High Dose Methotrexate (HD-MTX) toxicity can cause renal dysfunction in patients due to a presence of risk factors such as body mass index >25 kg/m2, comedication (salicylates, NSAID`s, sulfonamides, beta-lactam antibiotics, aminoglycosides), urine pH<7, iv fluid intake <3 l/m2/24 hours, hepatic dysfunction, renal insufficiency prior to HD-MTX, diarrhea and pleural effusions. To prevent renal dysfunction and further MTX toxicity Glucarpidase can be used which degrades MTX to its metabolites. Cases: A 17 year-old and a 14 year-old boy were treated with HD-MTX, developed renal insufficiency and were treated with Glucarpidase. In both patients unexpected renal dysfunction was seen still 3-4 weeks after treatment with Glucarpidase. A theoretic concern regarding the use of Glucarpidase is that the rapid formation of MTX metabolite called DAMPA, which is almost 10-fold less soluble than MTX, may lead to further renal toxicity by precipitation in the renal tubules. If we compare our patient data with data we found in the literature there is almost no difference in renal dysfunction duration between patients who got Glucarpidase (21 days) and those with only supportive therapy (19 and 12 days). After treatment with Glucarpidase the question on how and when to restart HDMTX therapy raised. The safe option for our two patients would be first a rechallange with 50-75% HD-MTX after a full recovery of the renal function. After the first rechallange kindey function and MTX levels should be closely monitored and if no problems are observed the second rechallange should be with 100% HD-MTX. If we closely look at our data and available data from the published articles there is a concern on how effective and safe Glucarpidase is. Glucarpidase should be given only in cases if supportive therapy is not effective enough in lowering MTX plasma levels. Even then, health care professionals should use Glucarpidase cautiously because of its uncertain benefits unpredictable side effect.