Symptoms following overdosage of desferrioxamine (Desferal). Is there a specific antidote?/nBackgro

Fråga: Symptoms following overdosage of desferrioxamine (Desferal). Is there a specific antidote?

Background: An 18-year-old man with a transfusion-dependent thalassemia major has been treated with desferrioxamine subcutaneously for many years. The last two months treatment has been given intravenously because the patient has refused administration the other way. Recently, after the second infusion (6000 mg during 24 hours) the patient developed nausea, a sensation of numbness and muscular cramp in the legs, a transient blurred vision and anxiety. Blood level of ferritin was 4000 ug/l (reference value 20-320 ug/l).

Communication with The Swedish Poison Information centre revealed no information.

Sammanfattning: The recommendation of desferroxiamine administered intravenously is a maximum dosage of 6000 mg in 24 hours, as in this patient. Circulatory, CNS, and gastrointestinal side-effects are regarded as symptoms following high doses of desferroxiamine. It is likely that the present symptoms are related to the fact that the maximum recommended dose has now been given intravenously. Signs and symptoms of overdosage may be eliminated by reducing the dose. Although, no antidote could be used in case of intoxication, desferroxiamine is readily dialyzable.

Svar: Questions concerning the use of desferrioxamine in the treatment of iron overload or poisoning have previously been dealt with in Drugline (1-5). Desferrioxamine chelates iron by forming a stable complex that prevents iron from entering into further chemical reactions (6). Desferrioxamine is eliminated both by metabolism and renal excretion (1).

Administration of high doses of desferrioxamine has been associated with visual and auditory neurotoxicity (3). Tachycardia, hypotension, and gastrointestinal symptoms have occasionally developed following overdosage. Blurred vision, cataracts, impaired peripheral colour and night vision, and retinal pigmentary abnormalities have been reported among visual disturbances (6). The auditory side effects reported have been tinnitus and hearing loss (6). In most cases, both visual and auditory neurotoxicity are reversible after drug withdrawal (3,6). According to a study, induction of neurotoxicity by subcutaneous desferroxiamine is dose-dependent and cannot be attributed to accumulation of the drug caused by slower clearance rates (7). Both symptomatic and asymptomatic patients had the same clearance rates (7). Signs and symptoms of overdosage may be eliminated by reducing the dosage of desferroxiamine (6). A study in patients with chronic renal failure on haemodialysis has shown a decrease of desferroxiamine in blood plasma concentration representing the transfer to the dialysis fluid (8).

No specific antidote could be found in the literature. However, it is recommended that an initial dose of 1000 mg should be administered intravenously at a rate not to exceed 15 mg/kg per hour. This may be followed by 500 mg every 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4-12 hours. The total amount administered should not exceed 6000 mg in 24 hours (6). 1 Drugline nr 11808 (year 1995)

2 Drugline nr 05128 (year 1986)
3 Drugline nr 05098 (year 1986)
4 Drugline nr 04497 (year 1985)
5 Drugline nr 03350 (year 1982)
6 Physicians Desk Reference (PDR)

7 Bentur Y, Koren G, Tesoro A, Carley H, Olivieri N, Freedman MH: Comparison of deferoxamine pharmacokinetics between asymptomatic thalassemic children and those exhibiting severe neurotoxicity. Clin Pharmacol Ther 1990; 47: 478-482 8 Allain P, Chaleil D, Mauras Y, Beaudeau G, Varin MC, Poignet JL, Ciancioni C, Ang KS, Cam G, Simon P: Pharmacokinetics of desferrioxamine and of its iron and aluminium chelates in patients on haemodialysis. Clin Chim Acta 1987; 170: 331-338