Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient

2020 ◽  
pp. 107815522095387 ◽  
Author(s):  
Irene Krämer ◽  
Jelena Rosentreter ◽  
Marius Fried ◽  
Michael Kühn
Keyword(s):  
Renal Failure ◽  
Significant Interaction ◽  
Rescue Therapy ◽  
Pharmacokinetic Interaction ◽  
Serum Levels ◽  
Calcium Folinate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Medicinal Products ◽  
Dose Methotrexate

Introduction Pharmacokinetic interaction of high-dose methotrexate (MTX) and other concomitantly administered renally secreted medicinal products may lead to insufficient methotrexate serum level decrease and significant MTX toxicity. Case report We report the case of an 18-year-old male patient treated with high-dose MTX for an osteosarcoma and with high-dose piperacillin-tazobactam at the same time. MTX serum levels were severely elevated 24 hours after the MTX infusion and did not decrease in accordance with the specific calcium folinate rescue protocol. The patient experienced renal failure accompanied by neurological symptoms, most consistent with MTX-related renal and CNS toxicity. Management and outcome: After discontinuation of piperacillin-tazobactam, intensified calcium folinate rescue therapy, and IV hydration, the MTX serum levels decreased appropriately, and toxicity symptoms resolved. Discussion Severe MTX-related toxicity, caused by drug-drug interaction, suggests that the concomitant use of high-dose MTX and high-dose piperacillin-tazobactam should be avoided generally.

Pharmacokinetic Interaction Between High-Dose Methotrexate and Oxacillin

2002 ◽  
Vol 24 (4) ◽  
pp. 570-572 ◽  
Author(s):  
Karine Titier ◽  
Fabrice Lagrange ◽  
Fabienne Péhourcq ◽  
Nicholas Moore ◽  
Mathieu Molimard
Keyword(s):  
Pharmacokinetic Interaction ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

2008 ◽  
Vol 50 (1) ◽  
pp. 154-156 ◽  
Author(s):  
Rita Turello ◽  
Katharina Rentsch ◽  
Ermindo Di Paolo ◽  
Maja Beck Popovic
Keyword(s):  
Renal Failure ◽  
Mthfr C677t ◽  
High Dose ◽  
High Dose Methotrexate ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Dose Methotrexate

Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure

2001 ◽  
Vol 47 (6) ◽  
pp. 537-540 ◽  
Author(s):  
Desirée van den Bongard ◽  
Ron Mathôt ◽  
Willem Boogerd ◽  
Jan Schornagel ◽  
Marcel Soesan ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Outpatient administration of high-dose methotrexate for osteosarcoma treatment in Brazil

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10038-10038 ◽  
Author(s):  
C. R. Macedo ◽  
A. M. Cappellano ◽  
D. T. Noguchi ◽  
A. P. Martinho ◽  
C. G. Dias ◽  
...  
Keyword(s):  
Adverse Events ◽  
Patient Adherence ◽  
Elevated Serum ◽  
Serum Levels ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Serious Adverse Events ◽  
Early Introduction ◽  
Dose Methotrexate ◽  
Metronomic Treatment

10038 Background: We describe the experience with outpatient administration of high dose methotrexate (HDMTX) and leucovorin rescue for osteosarcoma treatment at Instituto de Oncologia Pediátrica. Methods: HDMTX (12g/m2) is administered as part of the Brazilian Osteosarcoma Treatment Group Protocol in an ambulatory basis. Daily MTX serum levels and fluid controls follows until the serum level is <0,2 μ/L. Families were oriented to measure urinary pH and volume, PO intake and to adjust leucovorin dose as needed. To achieve treatment adherence, a family education program was developed. Concomitantly to HD chemotherapy, low dose oral cyclophosphamide and MTX (metronomic treatment) were provided to metastatic (M) patients. This is a retrospective analysis of the HDMTX courses administered between 2006 and 2008. Results: Out of 341 HDMTX infusions, administered to 42 patients, 42.5% had abnormal serum levels at hour 24, 8.8% at hour 48 and 33.2% at hour 72. After required interventions, 2.9% (n = 8) had serum levels >0.2 μ/L at hour 72 leading to delayed excretion. Of these, 7 had also creatinine elevation and main adverse events were mucositis, reversible transaminasis elevation and one sepsis. In the overall analysis, other toxicities included mucositis grade II (20%), nefrotoxicity (5.6%) and neutropenia grades III and IV (25.4%). Serious adverse events of seizure, allergic reaction, and Steven Johnson's Syndrome lead to suspension of future HDMTX administration in 4 patients (01 metastatic). The main differences found between M and non-M patients were 16.8% versus 8.7% of leucopenia grade IV and 12.1% versus 6.6% of anemia grades III and IV. Conclusions: Similar to other authors’ experience, outpatient administration of HDMTX lead to elevated serum levels in 42.5% of the infusions, demonstrating the importance of a well trained staff and early introduction of supportive therapies to avoid associated toxicities. To a developing country, this approach helps lowering treatment costs and infection risks and increases patient adherence to treatment, with acceptable toxicities, even with the introduction of metronomic treatment. No significant financial relationships to disclose.

scholarly journals Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy

2017 ◽  
Vol 5 ◽  
pp. 2050313X1770505 ◽  
Author(s):  
James Harms ◽  
Ayaz Khawaja ◽  
Maria Taylor ◽  
Xiaosi Han ◽  
Michal Mrug
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Rescue Therapy ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Renal Function Recovery ◽  
Function Recovery ◽  
Lethal Complications

Objectives: This case report describes two cases of high-dose methotrexate–induced nephrotoxicity: death in the case of conventional supportive care and successful renal function recovery in a patient treated with glucarpidase and continuous dialysis. Methods: High dose methotrexate is widely used for management of adult and pediatric malignancies. However, high-dose methotrexate–induced renal nephrotoxicity may cause severe, even lethal complications. Here we present examples of such outcomes. Results: We present one case of lethal high-dose methotrexate nephrotoxicity in a patient treated with conventional rescue therapy. We contrast this outcome with another patient with high-dose methotrexate–induced anuric acute kidney injury, who has recovered renal function following therapy with glucarpidase and continuous dialysis. Conclusions: This is only the second reported case of high-dose methotrexate–induced anuric acute kidney injury, and the only one with a reported clinical outcome. This first report of recovery from high-dose methotrexate–induced anuric acute kidney injury after glucarpidase administration supports available evidence pointing to the effectiveness of this therapy.

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