Auditory and Visual Toxicity During Deferoxamine Therapy in Transfusion-Dependent Patients

Abstract

Deferoxamine is a chelating agent that has extended the life expectancy of patients with thalassemia. In the 1980s, many investigators reported otologic and visual toxicity caused by deferoxamine. In July 1999 and 2 years later, the authors performed audiologic and ophthalmologic assessments in 30 transfusion-dependent patients receiving deferoxamine therapy (40-50 mg/kg per dose, subcutaneously for 8-10 hours, 4-7 days per week). In 1999, six patients (20%) had deferoxamine-related hearing impairment (>25 dB), all at high frequencies. Because the authors believed the benefits of chelation therapy outweighed the risk of ototoxicity, the dose of deferoxamine was not reduced. Two years later, the hearing impairment had not progressed in any of the patients. There was no association between ototoxicity and ferritin level. No patients had abnormalities of visual acuity or funduscopy in either 1999 or 2001. Based on this experience, deferoxamine at doses lower than 50 mg/kg/d was safe for the eyes and slightly toxic to the ears. The ototoxicity probably relates to individual susceptibility. Regular monitoring of auditory function and close follow-up of abnormal findings are recommended. According to this limited experience, reducing the dose or withdrawing deferoxamine might not be necessary if the hearing loss is stable in the face of ferritin levels above 2,000 ng/mL. Because of the relatively small patient numbers, more data are needed to confirm these conclusions.

The Incidence of Ototoxicity in Patients Using Iron Chelators

“…Although the "safe" dosage of DFO is accepted to be below 50 mg/kg/d [3,12] , we observed a high rate of DFO-related ototoxicity (31.9%). Thus, we believe that no dose of DFO should be considered totally safe.…”

“…DFO may cause growth retardation, sensorineural ototoxicity, ocular toxicity, and bone deformities [3,[10][11][12] . Although the exact mechanism has not been explained, ototoxicity in thalassemia patients has been attributed to DFO [3,6] ; this may occur through direct toxic effects on the cochlea and reduction of trace elements such as Zn, Cu, and Mn [9,11] .…”

“…The reported incidence of DFO-related ototoxicity varies from 3.8%-57% [3,5,6,13] . DFO-related ototoxicity was observed in 31.9% of patients given the drug in our study.…”

“…Deferoxamine (DFO; Desferal 500 mg; Novartis, Stein, Switzerland) was the first and, until recently, the preferred iron-chelating drug [1,2] . However, there have been several reports of DFO ototoxicity [1][2][3][4][5][6] , especially with long-term use and at higher doses. In recent years, deferiprone (Ferriprox 500 mg; Ontario, Canada) and deferasirox (Exjade 500 mg; Novartis, Stein, Switzerland) have largely replaced DFO due to their ease of use, as they can be taken orally.…”

Iron Overload and Iron Chelation Therapy in Pediatric Patients

“…24,25 The prolonged and burdensome administration, coupled with the adverse effects, can become a cause of low compliance, particularly in adolescent patients. Poor compliance has significant implications for the outcome of chelation therapy and survival in iron-overloaded pediatric patients, as many of these patients will require iron chelation therapy for the duration of their lives.…”