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Blood, 15 January 2008, Vol. 111, No. 2, pp. 483-484.
Oral iron chelation: new drug, old rulesHARVARD MEDICAL SCHOOL
The dose and schedule of an iron chelator, whether given parenterally or orally, is variable and depends on the rate of iron loading.
A cardinal rule of iron chelation therapy was established by Modell and her colleagues in the 1970s and reiterated in the 1990s.1,2 The dose and the schedule of deferoxamine must be adjusted to the rate of iron loading. If the rate of iron loading is increased by, let us say, an increased rate of hemolysis induced by the treatment of hepatitis C, the dose and frequency of the chelator must be increased pari passu. Cohen et al have shown this to be the case with respect to deferasirox. There might have been reason to hope that deferasirox would permit the physician and insurer to avoid the rule and save money. After all, deferasirox has a very long plasma half-life,3 whereas deferoxamine rapidly disappears from the circulation. Deferasirox is a member of a class of drugs that removes iron almost exclusively through the liver and gastrointestinal (GI) tract. A single dose can induce increased iron excretion for days, as the excreted unbound drug is repeatedly reabsorbed and travels through the enterohepatic circulation. In contrast, although deferoxamine removes iron through the stools and the urine, the effect of a single dose is very time-limited because it is not absorbed or, better, reabsorbed from the GI tract. One might also have hoped that the long half-life of deferasirox would protect the patient from the toxic effects of accelerating iron overload, because the circu-lating drug snaps up nontransferring bound iron and presumably protects the heart even though the hepatic iron load is increasing.3,4 Despite the above aspirations, clinical experience and the results of the studies of Cohen et al have already shown that the Modell rule has not been nullified. Iron load must be regularly monitored during treatment of chronic transfusion-dependent anemia, and chelator dose adjusted accordingly. Fortunately, new technology has made iron-load assessment much more practical. The so-called gold standard, the liver biopsy, is a bit tarnished because its accuracy is weakened by hepatic fibrosis. The superconducting quantum interference device (SQUID) is largely unavailable, terribly unwieldy, and poorly reproducible from machine to machine. But magnetic resonance imaging (MRI) methods have markedly improved, and are reproducible if each patient serves as his or her own control.5 Although the old rules have not changed, the advent of an oral iron chelator has made a huge difference for patients who require chronic transfusions. This is surely a boon for patients and for physicians, nurses, and parents who have struggled to achieve compliance with an unpleasant subcutaneous treatment regimen.
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests.
REFERENCES
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