The ototoxicity of deferoxamine mesylate

Kanno, Hidetaka; Yamanobe, Syu; Rybak, Leonard P.

doi:10.1016/0196-0709(95)90093-4

Cited by 18 publications

(10 citation statements)

References 19 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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The Incidence of Ototoxicity in Patients Using Iron Chelators

Derin

Azık²,

Topal³

et al. 2017

Int Adv Otol

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[7] .In this study, we aimed to identify the frequency of ototoxicity associated with the iron-chelating agents deferiprone, deferasirox, and DFO in transfusion-dependent patients. Ototoxicity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale, and correlations of ototoxicity with duration of therapy, ferritin, and pre-transfusion (pre-tx) Hb levels were assessed. MATERIALS and METHODS PatientsThis cross-sectional study included 55 transfusion-dependent patients who were referred to our Thalassemia Center between 2013 and 2015. The study protocol was approved by Ethics Committee of Muğla Sıtkı Koçman University, Medical School. 136The Incidence of Ototoxicity in Patients Using Iron Chelators OBJECTIVE: In this study, we aimed to detect the incidences of ototoxicity in patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to obtain more objective data. MATERIALS and METHODS:Fifty-five transfusion-dependent patients were evaluated in this study. The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin and hemoglobin levels, the type of iron chelator, and the duration of therapy of all the patients were recorded. RESULTS:Ototoxicity was observed in 15 patients (31.9 %), all of whom were taking DFO. The median age was 19.5 (6-43) in patients without ototoxicity and 29 (16-50) in those with ototoxicity; this difference was statistically significant (p<0.05). The median ferritin and pre-tx Hb levels were 1391 ng/mL and 9.06 mg/dL, respectively, in patients with ototoxicity and 986.7 ng/mL and 9.24 mg/dL, respectively, in those without ototoxicity; these differences were not significant (p>0.05). Ototoxicity was not observed in the eight patients who used only deferasirox and deferiprone. CONCLUSION:The ototoxicity incidence with DFO at doses below 50 mg/kg/day was 27.3%. Deferiprone and deferasirox were not associated with ototoxic effects in patients taking these drugs.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Incidence of Ototoxicity in Patients Using Iron Chelators

Derin

Azık²,

Topal³

et al. 2017

Int Adv Otol

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“…Neither deferoxamine nor 2,3-dihydroxybenzoic acid, the initially successful antioxidants [Song et al, 1997[Song et al, , 1998], fit these criteria. Deferoxamine, although well-established in clinical practice (Desferral TM ) has ototoxic potential in high doses, in both animals and patients [Kanno et al, 1995]. Dihydroxybenzoic acid, although found to be non-toxic in a year-long clinical study [Peterson et al, 1979], is not an approved drug today.…”

Section: Discussionmentioning

confidence: 99%

Aminoglycoside Antibiotics

Forge

Schacht²

2000

Audiol Neurotol

592

504

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In the 50 years since their discovery, the aminoglycoside antibiotics have seen unprecedented use. Discovered in the 1940s, they were the long-sought remedy for tuberculosis and other serious bacterial infections. The side effects of renal and auditory toxicity, however, led to a decline of their use in most countries in the 1970s and 1980s. Nevertheless, today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. This review first summarizes the history, chemistry, antibacterial actions and acute side effects of the drugs. It then details the pathophysiology of aminoglycoside ototoxicity including experimental and clinical observations, risk factors and incidence. Pharmacokinetics, cellular actions and our current understanding of the underlying molecular mechanisms of ototoxicity are discussed at length. The review concludes with recent advances towards therapeutic intervention to prevent aminoglycoside ototoxicity.

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“…The use of deferoxamine, however, raises certain questions regarding its safety in combination with ototoxic agents, since there are a number of reports of sensorineural hearing loss associated with the chronic use of deferoxamine in the treatment of thalassemia 23‐25 . The incidence rate of cochlear damage in a review of these reports varies from 3.8% to 57% 26 . Animal studies have suggested that high doses of deferoxamine(600 mg/kg for 6 weeks) are associated with elevated hearing thresholds, but studies at lower doses have failed to demonstrate an ototoxic effect 26‐28 .…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Neomycin Ototoxicity by Iron Chelation

1998

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Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.

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The ototoxicity of deferoxamine mesylate

Cited by 18 publications

References 19 publications

The Incidence of Ototoxicity in Patients Using Iron Chelators

The Incidence of Ototoxicity in Patients Using Iron Chelators

Aminoglycoside Antibiotics

Attenuation of Neomycin Ototoxicity by Iron Chelation

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