Deferoxamine is a parenterally administered iron chelating agent used to treat transfusion related chronic iron overload. Deferoxamine rarely causes serum aminotransferase elevations during therapy and has not been convincingly linked to instances of clinically apparent liver injury.
Deferoxamine (de” fer ox’ a meen) is parenterally administered iron chelating agent that binds iron with a high affinity and zinc and copper to a lesser extent. In clinical trials in patients with transfusion related iron overload, deferoxamine therapy lowered both circulating and tissue (cardiac, liver) iron levels and these reductions were maintained with long term subcutaneous infusions. Deferoxamine was approved for use in the United States in 1968 and current indications are for patients with transfusion related chronic iron overload as well as for acute iron overdose or intoxication. Deferoxamine is available in vials of 500 and 2000 mg for intravenous, intramuscular or subcutaneous administration generically and under the brand name Desferal. The subcutaneous routine is used most often for chronic iron overload and the typical dose is 1000 to 2000 mg per day (20 to 40 mg/kg/day) for 5 to 7 days a week given by continuous infusion over 8 to 24 hours. Side effects include injection site pain and infection, hypersensitivity reactions, arthralgias, myalgias, fever, headache, nausea and abdominal pain. Rare, but potentially severe adverse events of deferoxamine therapy include hearing and visual loss, acute renal failure and severe hypersensitivity reactions.
In large clinical trials, elevations in serum aminotransferase levels were rare in patients receiving deferoxamine and instances of acute, clinically apparent liver injury were not reported. Patients with transfusion related iron overload often have concurrent chronic hepatitis B or C, and elevations of serum aminotransferase levels during chelation therapy may be due to natural fluctuations in the underlying chronic liver disease activity. Nevertheless, elevations in serum aminotransferase levels and “hepatic dysfunction” are listed as potential adverse events in product labels for deferoxamine. After an early report of hepatitis occurring in patient on hemodialysis receiving deferoxamine to reduce aluminum levels, there have been no further published instances of clinically apparent liver injury that have been convincingly linked to deferoxamine therapy.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
The mechanism of injury accounting for serum enzyme elevations during deferoxamine therapy is not known. Deferoxamine is metabolized by plasma enzymes and the chelate is excreted in the urine, giving it a reddish color.
Outcome and Management
Serum aminotransferase elevations above 5 times the upper limit of normal (if confirmed) should lead to dose reduction or temporary cessation. Deferoxamine has not been implicated in cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome. There does not appear to be cross reactivity in risk for hepatic injury between deferoxamine and other iron chelators including deferiprone and deferasirox, both of which are more likely to be associated with liver injury usually in the form of transient serum enzyme elevations that resolve with dose adjustment or discontinuation of therapy.
Drug Class: Hematological Agents; Chelating
Agents, Iron Chelators
Other Drugs in the Subclass, Iron Chelators: Deferasirox, Deferiprone
REPRESENTATIVE TRADE NAMES
Deferoxamine – Generic, Desferal®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 27 December 2017
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Taher A, Sheikh-Taha M, Koussa S, Inati A, Neeman R, Mourad F. Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients. Eur J Haematol 2001; 67: 30-4. PubMed Citation (Comparison of 16 patients on oral deferiprone and 40 on subcutaneous deferoxamine therapy for thalassemia major and iron overload, AST elevations [≥2 times ULN, but transient in all] occurred in in 13 [81%] on deferiprone, but apparently none on deferoxamine).
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Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. PubMed Citation (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, no case was attributed to deferoxamine or deferiprone, but 1 was due to deferasirox, a 54 year old woman with hemochromatosis who developed ALT elevations [rising from 25 to 305 U/L] without symptoms or jaundice a month after starting deferasirox that resolved rapidly with stopping and recurred upon restarting).
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iron chelators in young patients with haemoglobinopathies. Eur J Haematol 2017; 98: 198-217. PubMed Citation (Review of literature on safety of iron chelators in young patients reported "increased liver enzymes" in 4% of subjects on deferoxamine, 6% on deferprone and 20% on deferasirox; no mention of clinically apparent liver injury).
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