Deferiprone, a bidentate iron chelator cleared predominantly via the kidney, was approved by the FDA in 2011 as a second-line oral chelator for patients with transfusional iron overload due to thalassemia. Compared to deferasirox, deferiprone appears to be relatively more efficient in decreasing cardiac iron but less efficient in decreasing hepatic iron. Because neutropenia has occurred in 5–10% of patients, with agranulocytosis in approximately 1%, regular hematologic monitoring is recommended.
Magnetic resonance imaging has been increasingly used to evaluate cardiac and hepatic iron burden and to guide iron chelation therapy. Regimens that combine iron-chelating agents have been used in cases when monotherapy has yielded suboptimal results.
Ferric hexacyanoferrate (insoluble Prussian blue) is a hydrated crystalline compound in which Fe2+ and Fe3+ atoms are coordinated with cyanide groups in a cubic lattice structure. Although used as a dark blue commercial pigment for nearly 300 years, it was only three decades ago that its potential usefulness as a pharmaceutical chelator was recognized. Primarily by ion exchange, and secondarily by mechanical trapping or adsorption, the compound has high affinity for certain univalent cations, particularly cesium and thallium. Used as an oral drug, insoluble Prussian blue undergoes minimal gastrointestinal absorption (<1%). Because the complexes it forms with cesium or thallium are nonabsorbable, oral administration of the chelator diminishes intestinal absorption or interrupts enterohepatic and enteroenteric circulation of these cations, thereby accelerating their elimination in the feces. In clinical case series, the use of Prussian blue has been associated with a decline in the biologic half-life (ie, in vivo retention) of radioactive cesium and thallium.
In 2003, the FDA approved Prussian blue for the treatment of contamination with radioactive cesium (137Cs) and intoxication with thallium salts. Approval was prompted by concern over potential widespread human contamination with radioactive cesium caused by terrorist use of a radioactive dispersal device (“dirty bomb”). The drug is part of the Strategic National Stockpile of pharmaceuticals and medical material maintained by the CDC (https://www.cdc.gov/phpr/stockpile/). (Note: Although soluble forms of Prussian blue, such as potassium ferric hexacyanoferrate, may have better utility in thallium poisoning, only the insoluble form is currently available as a pharmaceutical.)
After exposure to 137Cs or thallium salts, the approved adult dosage of Prussian blue is 3 g orally three times a day; the corresponding pediatric dosage (2–12 years of age) is 1 g orally three times a day. Serial monitoring of urine and fecal radioactivity (137Cs) and urinary thallium concentrations can guide the recommended duration of therapy. Adjunctive supportive care for possible acute radiation illness (137Cs) or systemic thallium toxicity should be instituted as needed.
Prussian blue has not been associated with significant adverse effects. Constipation, which may occur in some cases, should be treated with laxatives or increased dietary fiber.
GENERIC NAME AVAILABLE AS Deferasirox Exjade, Jadenu Deferiprone Ferriprox
Deferoxamine Generic, Desferal
Penicillamine Cuprimine, Depen
Succimer Chemet, Succicaptal (in Europe)
Advisory Committee on Childhood Lead Poisoning Prevention of the Centers for Disease Control and Prevention. Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention. CDC: Atlanta, GA. 2012. http:// www.cdc.gov/nceh/lead/ACCLPP/Final_Document_030712.pdf.