This concerns a 9 year old girl who is on peritonealdialysis. She will now get desferoxamin to trea

Fråga: This concerns a 9 year old girl who is on peritonealdialysis. She will now get desferoxamin to treat aluminium deposition. She is on diazepam 10 mg daily as prophylaxis for epileptic fits. Is there any risk for interaction analogously to the report by Blake et al who argue that two patients on prochlorperazine developed 2-3 days´ unconsciousness when desferoxamin was given?

Sammanfattning: There are no clinical reports or theoretical support of an interaction between desferroxamine and diazepam.

Svar: Desferoxamine is an iron chelating agent used in the treatment of chronic iron intoxication (hemacromatosis, hemosiderosis or transfusional iron overload) and acute iron poisoning. It is also used to treat dialysis aluminium intoxication (1). Desferoxamine is excreted through the kidneys (2).

Administration of high doses of desferroxamine has been recently associated with visual and auditory neurotoxicity (3,4).

There are no reports in the literature concerning an interaction between desferroxamine and diazepam. A metabolic interaction is unlikely to occur since desferroxamine is metabolized by plasma enzymes while diazepam is oxidized by liver microsomes, in a cytochrome P-450 dependent reaction. Moreover, although desferroxamine may inhibit some Fe-dependent enzymatic reactions (5) it does not remove iron from cytochromes, i.e. cytochrome P-450, not affecting the function of the main system involved in drug metabolism. In this regard, we performed in our laboratory an experiment showing no effect of different desferroxamine concentrations on the hydroxylation of the tricyclic antidepressant desipramine in human liver microsomes.

Blake et al (6) have recently reported that concurrent administration of desferroxamine and prochlorperazine resulted in loss of consciosness in two patients. They fully recovered after 48-72 hours. On the basis of in vivo/in vitro studies the authors speculate that the two drugs act synergistically, probably resulting in enhanced fluxes of intra/extra-cellular iron/copper disturbing noradrenergic and serotominergic systems. It is impossible to predict if a similar interaction could occur between desferroxamine and diazepam, but it seems unlikely since diazepam is different in the chemical structure and in the mechanism of action from both desferroxamine and prochlorperazine. 1 Ackrill P, Ralston AJ, Day JP, Hodge KC: Successful removal of aluminium from patient with dialysis encephalopathy. Lancet 1980; II: 692-693 2 Goodman and Gilman, The pharmacological basis of therapeutics, 1985; 7th ed (utan källreferens) 3 Olivieri NF, Buncic JR, Chew E, Gallant T, Harrison RV, Keenan N, Logan W, Mitchell D, Ricci G, Skarf B, Taylor M, Freedman MH: Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med 1986; 314: 869-873 4 Drugline nr 05098 5 Kirkun G, Cederbaum AI: Stereochemical studies on the cytochrome P-450 and hydroxyl radical dependent pathways of 2-butanol oxidation by microsomes from chow-fed, phenobarbital-treated and ethanol-treated rats. Biochemistry 1984; 23: 5489-5494 6 Blake DR, Winyard P, Lunec J, Williams A, Good PA, Crewes SJ, Gutteridge JMC, Rowley D, Halliwell B, Cornish A, Hider RC: Cerebral and ocular toxicity induced by desferrioxamine. Q J Med 1985; New Series 56: 345-355