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https://www.readbyqxmd.com/read/28221265/acute-liver-failure-during-deferasirox-chelation-a-toxicity-worth-considering
#1
Nathan Menaker, Katharine Halligan, Natasha Shur, John Paige, Matthew Hickling, Anne Nepo, Lauren Weintraub
This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox.
February 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28221264/efficacy-and-safety-of-combined-oral-chelation-with-deferiprone-and-deferasirox-in-children-with-%C3%AE-thalassemia-major-an-experience-from-north-india
#2
Nupur Parakh, Jagdish Chandra, Sunita Sharma, Bhavna Dhingra, Rajesh Jain, DeoNath Mahto
OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years...
February 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28185140/cost-utility-analysis-of-three-iron-chelators-used-in-monotherapy-for-the-treatment-of-chronic-iron-overload-in-%C3%AE-thalassaemia-major-patients-an-italian-perspective
#3
Alessia Pepe, Giuseppe Rossi, Anthony Bentley, Maria Caterina Putti, Ludovica Frizziero, Domenico Giuseppe D'Ascola, Liana Cuccia, Anna Spasiano, Aldo Filosa, Vincenzo Caruso, Aishah Hanif, Antonella Meloni
PURPOSE: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. METHODS: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY...
February 10, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28142202/new-film-coated-tablet-formulation-of-deferasirox-is-well-tolerated-in-patients-with-thalassemia-or-lower-risk-mds-results-of-the-randomized-phase-ii-eclipse-study
#4
Ali T Taher, Raffaella Origa, Silverio Perrotta, Alexandra Kourakli, Giovan Battista Ruffo, Antonis Kattamis, Ai-Sim Goh, Annelore Cortoos, Vicky Huang, Marine Weill, Raquel Merino Herranz, John B Porter
Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes...
January 31, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28141745/deferasirox-iron-complex-formation-ratio-as-an-indicator-of-long-term-chelation-efficacy-in-%C3%AE-thalassemia-major
#5
Meng-Yao Lu, Ting-Hao Lin, Po-Hung Chiang, Pei-Hsin Kuo, Ning Wang, Wen-Hsin Wu, Kai-Hsin Lin, Tzu-Hua Wu
BACKGROUND: β-Thalassemia major patients with higher total drug levels (deferasirox [DEFR] plus its iron complex) do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values. METHODS: Patients' steady-state drug levels at trough (Ctrough) and 2 hours post-dose (C2h) were determined. Since iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours post-dose...
January 30, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28140713/deferasirox-has-strong-anti-leukemia-activity-but-may-antagonize-theanti-leukemia-effect-of-doxorubicin
#6
Yu-Chien Chang, Wen-Jyi Lo, Yu-Ting Huang, Chaio-Lin Lin, Chiu-Che Feng, Hsin-Ting Lin, Hsu-Chen Cheng, Su-Peng Yeh
Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28139717/deferasirox-induced-iron-depletion-promotes-bclxl-downregulation-and-death-of-proximal-tubular-cells
#7
Diego Martin-Sanchez, Angel Gallegos-Villalobos, Miguel Fontecha-Barriuso, Susana Carrasco, Maria Dolores Sanchez-Niño, Francisco J Lopez-Hernandez, Marta Ruiz-Ortega, Jesus Egido, Alberto Ortiz, Ana Belén Sanz
Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101313/a-young-adult-with-unintended-acute-intravenous-iron-intoxication-treated-with-oral-chelation-the-use-of-liver-ferriscan-for-diagnosing-and-monitoring-tissue-iron-load
#8
Mohamed Yassin, Ashraf T Soliman, Vincenzo De Sanctis, Abbas Moustafa, Sandra Abou Samaan, Abdulqadir Nashwan
Acute iron intoxication (FeI) in humans has not been adequately studied. The manifestation of FeI, defined as a serum iron concentration >300 μg/dL (55 μmol/L) within 12 hours of ingestion, include various symptoms appearing in progressive stages. Systemic toxicity is expected with an intake of 60 mg/kg. A 27-year-old female nurse presented with unintended acute intravenous iron intoxication (FeI) a week after self-injecting herself with 20 ampoules of IV iron (4,000 mg elemental iron, 60 mg/kg). She had stable vital signs and mild hepatic tenderness...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28008230/efficacy-and-safety-of-iron-chelation-therapy-with-deferoxamine-deferiprone-and-deferasirox-for-the-treatment-of-iron-loaded-patients-with-nontransfusion-dependent-thalassemia-syndromes
#9
COMMENT
Ali T Taher, John B Porter, Antonis Kattamis, Vip Viprakasit, M Domenica Cappellini
No abstract text is available yet for this article.
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27994488/an-unfortunate-case-of-acquired-hemochromatosis-a-case-report-review-of-the-clinical-presentation-diagnosis-management-and-prognosis
#10
Anam Tariq, Kevin Westra, Arben Santo
BACKGROUND: While blood transfusions are commonly used for prophylaxis and treatment for acute chest syndromes and strokes in sickle cell patients, accumulation of excess iron resulting in secondary hemochromatosis remains a rare disease. Chelation is the mainstay for preventing and treating iron overload to deter potential end-organ damages; it is rare when therapy fails. CASE REPORT: A 52-year-old African American woman with chronic anemia secondary to sickle cell anemia and history of multiple blood transfusions presented with elevated serum ferritin (8000 ng/mL) and bilirubin (16...
2016: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/27928480/a-review-on-iron-chelators-in-treatment-of-iron-overload-syndromes
#11
REVIEW
Naser Mobarra, Mehrnoosh Shanaki, Hassan Ehteram, Hajar Nasiri, Mehdi Sahmani, Mohsen Saeidi, Mehdi Goudarzi, Hoda Pourkarim, Mehdi Azad
Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality...
October 1, 2016: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/27893351/management-of-iron-overload-in-myelodysplastic-syndromes-combined-deferasirox-and-deferoxamine-in-a-patient-with-liver-disease
#12
Claudio Cerchione, Giuseppe Cerciello, Simona Avilia, Roberta Della Pepa, Novella Pugliese, Marco Picardi, Lucio Catalano, Fabrizio Pane
No abstract text is available yet for this article.
October 24, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/27893170/safety-profiles-of-iron-chelators-in-young-patients-with-haemoglobinopathies
#13
REVIEW
Sebastian Botzenhardt, Niya Li, Esther W Chan, Chor Wing Sing, Ian C K Wong, Antje Neubert
BACKGROUND: This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies. METHODS: Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms...
March 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/27881236/deferasirox-pharmacokinetics-evaluation-in-a-woman-with-hereditary-haemochromatosis-and-heterozygous-%C3%AE-thalassaemia
#14
Sarah Allegra, Silvia De Francia, Filomena Longo, Davide Massano, Jessica Cusato, Arianna Arduino, Elisa Pirro, Antonio Piga, Antonio D'Avolio
We present the deferasirox pharmacokinetics evaluation of a female patient on iron chelation, for the interesting findings from her genetic background (hereditary haemochromatosis and heterozygous β-thalassaemia) and clinical history (ileostomy; iron overload from transfusions). Drug plasma concentrations were measured by an HPLC-UV validated method, before and after ileum resection. Area under deferasirox concentration curve over 24h (AUC) values were determined by the mixed log-linear rule, using Kinetica software...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27879229/the-incidence-of-ototoxicity-in-patients-using-iron-chelators
#15
Serhan Derin, Fatih Mehmet Azık, Yaşar Topal, Hatice Topal, Volkan Karakuş, Petek Uzay Çetinkaya, Murat Şahan, Tansel Erdem Azık, Can Naci Kocabaş
OBJECTIVE: In this study, we aimed to detect the incidences of ototoxicity in patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to obtain more objective data. MATERIALS AND METHODS: Fifty-five transfusion-dependent patients were evaluated in this study. The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin and hemoglobin levels, the type of iron chelator, and the duration of therapy of all the patients were recorded...
November 23, 2016: Journal of International Advanced Otology
https://www.readbyqxmd.com/read/27859648/limitations-of-serum-ferritin-to-predict-liver-iron-concentration-responses-to-deferasirox-therapy-in-patients-with-transfusion-dependent-thalassaemia
#16
MULTICENTER STUDY
John B Porter, Mohsen Elalfy, Ali Taher, Yesim Aydinok, Szu-Hee Lee, Pranee Sutcharitchan, Ali El-Ali, Jackie Han, Amal El-Beshlawy
BACKGROUND: In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. OBJECTIVES AND METHODS: This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox...
March 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/27833388/effects-of-an-oral-iron-chelator-deferasirox-on-advanced-hepatocellular-carcinoma
#17
Issei Saeki, Naoki Yamamoto, Takahiro Yamasaki, Taro Takami, Masaki Maeda, Koichi Fujisawa, Takuya Iwamoto, Toshihiko Matsumoto, Isao Hidaka, Tsuyoshi Ishikawa, Koichi Uchida, Kenji Tani, Isao Sakaida
AIM: To evaluate the inhibitory effects of deferasirox (DFX) against hepatocellular carcinoma (HCC) through basic and clinical studies. METHODS: In the basic study, the effect of DFX was investigated in three hepatoma cell lines (HepG2, Hep3B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day...
October 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27809710/the-questioning-for-routine-monthly-monitoring-of-proteinuria-in-patients-with-%C3%AE-thalassemia-on-deferasirox-chelation
#18
Turan Bayhan, Şule Ünal, Ozan Ünlü, Hakan Küçüker, Anıl Doğukan Tutal, Erdem Karabulut, Fatma Gümrük
BACKGROUND: Iron chelation therapy is one of the mainstays of the management of the patients with β-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. METHODS: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox...
November 3, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27771776/multidisciplinary-evaluation-at-baseline-and-during-treatment-improves-the-rate-of-compliance-and-efficacy-of-deferasirox-in-elderly-myelodysplastic-patients
#19
Lisette Del Corso, Lucia Biale, Emanuele Luigi Parodi, Rodolfo Russo, Rosa Filiberti, Eleonora Arboscello
BACKGROUND: Deferasirox (DFX) is used to reduce iron levels in patients with myelodysplastic syndrome (MDS) who develop iron overload after chronic red blood cell infusions. However, DFX can be associated with renal and gastrointestinal toxicities, which may cause treatment interruption or discontinuation. This study aimed to determine the effectiveness and safety of DFX in patients with MDS. METHODS: This multicenter, retrospective, observational study was conducted at two hospitals in Italy...
October 22, 2016: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27697722/determination-of-deferasirox-in-human-plasma-by-short-end-injection-and-sweeping-with-a-field-amplified-sample-stacking-and-micellar-electrokinetic-chromatography
#20
Hung-Ju Lin, Kun-Pin Hsieh, Shyh-Shin Chiou, Hwang-Shang Kou, Shou-Mei Wu
A field-amplified sample stacking-sweeping micellar electrokinetic chromatography with short-end injection was established for determination of deferasirox (DFX) in plasma. DFX was extracted from plasma and reconstituted with deionized water (lower conductivity solution). Capillary (effective length, 10cm) was filled with background electrolyte (40mM phosphate buffer, pH 4.5, containing 20% methanol). After sample loading from outlet end at 5psi for 15s, separation was carried out by applying high voltage at 15kV for 10min...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
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