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  • 1
    In: Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 89, No. 1 ( 2022-01), p. 41-48
    Abstract: High-dose methotrexate (HDMTX)-associated acute kidney injury with delayed MTX clearance has been linked to an excess in MTX-induced toxicities. Glucarpidase is a recombinant enzyme that rapidly hydrolyzes MTX into non-toxic metabolites. The recommended dose of glucarpidase is 50 U/kg, which has never been formally established in a dose finding study in humans. Few case reports, mostly in children, suggest that lower doses of glucarpidase might be equally effective in lowering MTX levels. Methods Seven patients with toxic MTX plasma concentrations following HDMTX therapy were treated with half-dose glucarpidase (mean 25 U/kg, range 17–32 U/kg). MTX levels were measured immunologically as well as by liquid chromatography–mass spectrometry (LC–MS). Toxicities were assessed according to National Cancer Institute—Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results All patients experienced HDMTX-associated kidney injury (median increase in creatinine levels within 48 h after HDMTX initiation compared to baseline of 251%, range 80–455%) and showed toxic MTX plasma concentrations (range 3.1–182.4 µmol/L) before glucarpidase injection. The drug was administered 42–70 h after HDMTX initiation. Within one day after glucarpidase injection, MTX plasma concentrations decreased by ≥ 97.7% translating into levels of 0.02–2.03 µmol/L. MTX rebound was detected in plasma 42–73 h after glucarpidase initiation, but concentrations remained consistent at  〈  10 µmol/L. Conclusion Half-dose glucarpidase seems to be effective in lowering MTX levels to concentrations manageable with continued intensified folinic acid rescue.
    Type of Medium: Online Resource
    ISSN: 0344-5704 , 1432-0843
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458488-8
    SSG: 15,3
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  • 2
    In: Chemotherapy, S. Karger AG, Vol. 64, No. 4 ( 2019), p. 210-214
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Pegylated asparaginase may induce prolonged hypertriglyceridemia. To date, there is no standard management of this complication. Here, we present a case report of pegylated asparaginase-induced hypertriglyceridemia and hepatotoxicity successfully treated with continuous intravenous infusion of insulin and heparin. 〈 b 〉 〈 i 〉 Case Presentation: 〈 /i 〉 〈 /b 〉 A 51-year-old male patient with lymphoid blast crisis of chronic myelogenous leukemia was treated with pegylated asparaginase. The patient developed severe hypertriglyceridemia. Supportive therapy with low-fat diet, fibric acids, and omega-3 fatty acids was not successful, and later, the patient developed high-grade hepatotoxicity. Like hypertriglyceridemia-induced pancreatitis, continuous intravenous infusion of insulin and heparin was initiated. The level of triglyceride and cholesterol decreased rapidly within 4 days. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In case of severe pegylated asparaginase-induced hypertriglyceridemia, continuous intravenous infusion of insulin and heparin can reduce rapidly and safely the triglyceride level. Controlled trials are needed to address this important issue.
    Type of Medium: Online Resource
    ISSN: 0009-3157 , 1421-9794
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 1482111-4
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  • 3
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 78, No. 4 ( 2014-10), p. 908-917
    Abstract: Vitamin‐K antagonists (VKA) and non‐vitamin‐K dependent oral anticoagulants ( NOAC ) have been approved for anticoagulation in venous thromboembolism ( VTE ) and atrial fibrillation and patients previously treated with VKA are switched to NOAC therapy. Safety data for this switching are urgently needed. Methods Using data from a large regional prospective registry of daily care NOAC patients, we evaluated the safety of switching anticoagulation from VKA to dabigatran or rivaroxaban. Switching procedures and cardiovascular and bleeding events occurring within 30 days after switching were centrally adjudicated. Results Between 1 O ctober 2011 and 18 J une 2013, 2231 patients were enrolled. Of these, 716 patients were switched from VKA to NOAC . Only 410 of the 546 evaluable patients (75.1%) had a recorded INR measurement within the 10 days preceding or following the end of VKA treatment (mean INR 2.4). As of day 30, major bleeding complications were rare (0.3%; 95% CI 0.0, 1.0) with an overall bleeding rate of 12.2% (95% CI 9.8, 14.8). Major cardiovascular events occurred in 0.8% (95% CI 0.3, 1.8). There was no significant difference in outcome event rates between the subgroups of patients with or without INR testing. Conclusion In daily care, only 75% of VKA patients have an INR measurement documented before NOAC are started. On average, NOAC are started within 2 to 5 days after the last intake of VKA . However, at 30 days follow‐up cardiovascular events or major bleedings were rare both in patients with and without INR testing. However, switching procedures need to be further evaluated in larger cohorts of patients.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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