Case 40
Atul B. Mehta, Keith Gomez in Clinical Haematology, 2017
Iron chelation therapy is usually administered in the form of parenteral desferrioxamine (DFO, typically given by subcutaneous infusion over 12 hours, five nights each week, with oral vitamin C). Side effects of DFO include sensory changes (hearing loss, visual defects), and bone and cartilage abnormalities. The necessity of parenteral administration contributes toward poor compliance. Deferasirox is a once-daily oral iron chelator which can cause renal and gastrointestinal (GI) disturbances but is generally well tolerated. Deferiprone is an oral iron chelator which seems to be particularly effective at removing cardiac iron. Side effects include agranulocytosis (1%), arthralgia and GI disturbances. Cardiac iron is best measured by magnetic resonance imaging (MRI). Haemopoietic stem cell or umbilical cord stem cell transplantation is curative for selected patients.
Iron-chelating effect of Caesalpinia sappan extract under conditions of iron overload
Robert Hofstra, Noriyuki Koibuchi, Suthat Fucharoen in Advances in Biomolecular Medicine, 2017
In this study, Deferiprone showed the same ability to sappan wood extract administration at variation doses in lowering levels of hepatic iron in rats, which indicates that the Deferiprone chelates iron effectively in rats, both in plasma and tissue. Deferiprone has a function of iron chelation because it can penetrate the cell membrane, act as intracellular iron chelator, and can bind to free iron in plasma. In patients with thalassemia, Deferiprone is the first option because it is more practical, comfortable, and cheaper (Hoffbrand et al., 2012).
Neoliberalist approaches to healthcare and the transnational pharmaceutical corporations
Théodore H MacDonald in Removing the Barriers to Global Health Equity, 2018
Deferiprone helps clear iron from the blood which builds up in patients with thalassaemia and can prove fatal. At first the trial went well and Dr Olivieri published promising results in the New England Journal of Medicine. Then she noticed worrying liver changes in some of her patients. She raised her concerns with the company and tried to find a way of adapting the trial. But she was unprepared for the response of the company, whose potential million-dollar drug she was now questioning.
An evaluation of deferiprone as twice-a-day tablets or in combination therapy for the treatment of transfusional iron overload in thalassemia syndromes
Published in Expert Review of Hematology, 2023
Richa Shah, Aashaka Shah, Sherif M. Badawy
Deferiprone has been FDA approved for use in patients with transfusional iron overload since 2011 in the form of three times daily tablets or oral solution. More recently, it has gained FDA approval for use as twice-daily tablets. Compared to other iron chelators, such as DFO and DFX, DFP has shown similar efficacy in decreasing systemic iron overload. DFP decreases serum ferritin and liver and myocardial iron content, as well as increases urinary iron excretion. DFP has also been shown to have higher medication adherence and an increased ability to decrease cardiac iron stores compared to other iron chelators. Common side effects of DFP include neutropenia, gastrointestinal disturbances, joint pain, and an increase in liver enzymes. Although not as common, agranulocytosis is a serious potential side effect that patients should be monitored for while receiving DFP treatment. However, studies have shown that agranulocytosis is reversible with cessation of the medication. Overall, deferiprone is an effective treatment for transfusional iron overload. Dual chelation regimens involving DFP, as well DFP’s recent approval for twice-daily usage, are anticipated to increase the use and reach of DFP in the coming years.
Emerging therapies in Friedreich’s Ataxia
Published in Expert Review of Neurotherapeutics, 2020
Theresa A. Zesiewicz, Joshua Hancock, Shaila D. Ghanekar, Sheng-Han Kuo, Carlos A. Dohse, Joshua Vega
FRDA causes a marked reduction of frataxin, leading to oxidative damage and subsequent neurodegeneration [54]. An important role of frataxin is to assist in the formation of mitochondrial iron-sulfur (Fe-S) clusters (ISC) [55], which are vital to cellular respiration and energy production [56]. Iron accumulation has been found in the cell models and FRDA patient tissues; therefore, iron chelators might be an appealing strategy for FRDA. Deferiprone is an orally administered iron chelator with good permeability that has been tested as a treatment of FRDA. One double-blind, placebo-controlled study randomized 72 FRDA patients to receive deferiprone 20, 40, or 60 mg/kg/day or placebo for 6 months [57]. Deferiprone was generally well tolerated at the lowest dose of 20 mg/kg/day, but two patients experienced worsening ataxia taking the highest dose of 60 mg/kg/day. An additional patient experienced reversible neutropenia while taking 20 mg/kg/day. There were no significant changes in the FARS in the 20 mg/kg/day group, and worsening was observed in those patients who received 40 mg/kg/day. However, patients in all dose groups had a decrease in cardiac hypertrophy [57]. The future of iron chelators as a treatment for FRDA remains unclear at present.
Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform
Published in Expert Review of Hematology, 2018
Peter Valent, Reinhard Stauder, Igor Theurl, Klaus Geissler, Thamer Sliwa, Wolfgang R. Sperr, Peter Bettelheim, Heinz Sill, Michael Pfeilstöcker
With regard to the drug of choice, more and more data suggest that deferasirox is an effective and relatively safe agent. Therefore, our expert group is of the opinion that deferasirox should be considered as first-line standard therapy in all patients. Other alternative chelators (desferoxamine and deferiprone) are also available and should be administered in case of intolerance against deferasirox, with recognition of potential side effects. Whereas the major side effect of deferiprone is neutropenia, the most frequent adverse events seen during deferasirox therapy are gastrointestinal events and abnormal kidney function. However, these side effects are dose-dependent and can be largely prevented in most patients by a step-wise dose escalation and by avoiding unnecessary high doses of the drug.
Related Knowledge Centers
- Chelation
- Cirrhosis
- Hematology
- Iron
- Pharmaceutical Industry
- Medication
- Thalassemia
- Accelerated Approval