Acute kidney injury, agranulocytosis, drug-induced liver injury, and posterior reversible encephalopathy syndrome caused by high-dose methotrexate—possible role of low activity ABC and SLC drug transporters

2018 ◽  
Vol 74 (9) ◽  
pp. 1191-1192 ◽  
Author(s):  
L. Bielen ◽  
I. Kralj ◽  
Ela Ćurčić ◽  
M. Vodanović ◽  
A. Boban ◽  
...  
2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.


2020 ◽  
pp. 107815522092745
Author(s):  
Stephanie F Matta ◽  
Leslie A Gieselman ◽  
Robert S Mancini

Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol ( p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10034-10034
Author(s):  
Andrew J. Bukowinski ◽  
Tomoyuki Mizuno ◽  
Tsuyoshi Fukuda ◽  
A.a. Vinks ◽  
Stuart Goldstein ◽  
...  

2014 ◽  
Vol 15 (22) ◽  
pp. 9823-9829 ◽  
Author(s):  
Worawut Choeyprasert ◽  
Samart Pakakasama ◽  
Nongnuch Sirachainan ◽  
Duantida Songdej ◽  
Ampaiwan Chuansumrit ◽  
...  

Chemotherapy ◽  
2018 ◽  
Vol 63 (2) ◽  
pp. 100-106 ◽  
Author(s):  
Dao-Hai Cheng ◽  
Hua Lu ◽  
Tao-Tao Liu ◽  
Xiao-Qin Zou ◽  
Hui-Mei Pang

Aims: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. Methods: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016. The clinical data were compared between the groups of children with development of AKI and those without. Risk factors were identified by multiple logistic regression analysis, and the diagnostic performance of plasma MTX concentration was evaluated by receiver operating characteristic (ROC) curve analysis. Results: AKI was observed in 88 patients (26.2%) and 104 courses (7.8%). Binary logistic regression revealed that age (OR 1.349; p = 0.005), first HDMTX course (OR 1.767; p = 0.013), MTX dose per body surface area (BSA; OR 1.944; p = 0.015), and baseline serum total protein (OR 0.929; p = 0.021) significantly correlated with AKI. The area under the ROC for 48-h plasma MTX concentration was 0.890 (95% CI 0.850–0.930), and sensitivity and specificity values of the cut-off value were 78.8 and 90.4%, respectively. Conclusion: Increasing age, higher MTX dose per BSA, lower baseline serum protein, and first HDMTX course were significant risk factors for developing HDMTX-induced AKI in childhood ALL. The threshold of 48-h MTX plasma concentration is valuable for the prediction of HDMTX-induced AKI.


2020 ◽  
Vol 38 (4) ◽  
pp. 584-588
Author(s):  
Irina Amitai ◽  
Uri Rozovski ◽  
Reem El‐Saleh ◽  
Shai Shimony ◽  
Daniel Shepshelovich ◽  
...  

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