Deferiprone

(BAN, rINN)
Deferiprone Chemical formula
Synonyms: CP-20; Deferipron; Deferiprona; Défériprone; Deferiproni; Deferipronum; Dimethylhydroxypyridone; L1. 1,2-Dimethyl-3-hydroxypyrid-4-one; 3-Hydroxy-1,2-dimethyl-4-pyridone.
Cyrillic synonym: Деферипрон.

💊 Chemical information

Chemical formula: C7H9NO2 = 139.2.
CAS — 30652-11-0.
ATC — V03AC02.
ATC Vet — QV03AC02.

💊 Adverse Effects and Precautions

Deferiprone has been shown to cause neutropenia and should not be used in neutropenic patients; the neutrophil count should be monitored weekly and treatment should be stopped if neutropenia develops. Agranulocytosis has also occurred. Patients should be advised to seek immediate medical attention if symptoms indicative of infection such as fever, sore throat, or flu-like symptoms occur. Gastrointestinal disorders such as diarrhoea, nausea, vomiting, and abdominal pain are common during deferiprone treatment and may require a temporary reduction in dose. A reddish-brown discoloration of the urine is also common. Other adverse effects that have been reported include arthralgia and increased liver enzymes. Deferiprone may reduce plasma-zinc concentrations and zinc supplements may be required. Deferiprone is teratogenic in animals and should not be used during pregnancy. Women of child-bearing potential should be advised to use contraceptive measures during treatment with deferiprone. Caution is advised in patients with hepatic or renal impairment.

Effects on the blood.

Agranulocytosis, in some cases fatal, has been reported in association with deferiprone use.1,2
1. Henter J-I, Karlén J. Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. Blood 2007; 109: 5157–9
2. Anonymous. Deferiprone: agranulocytosis and neurological disorders. Prescrire Int 2007; 16: 72.

Overdosage.

Neurological disorders were reported by the manufacturer and the French pharmacovigilance authorities in 2 children aged 7 and 9 who had been treated with deferiprone doses at 2 ⁄ times the highest recommended dose of 100 mg/kg daily. The children were treated for 1 and 2 years, respectively, and developed nystagmus, gait disorders, ataxia, dystonia, and, in one case, psychomotor retardation. These disorders gradually improved after deferiprone was stopped.1
1. Agence française de sécurité sanitaire des produits de santé/Laboratoires Chiesi, France. Risque d’agranulocytoses fatales et de troubles neurologiques lors de l’utilisation de Ferriprox (défériprone) (issued 1st September, 2006). Available at: http:// agmed.sante.gouv.fr/htm/10/filltrpsc/lp060901.pdf (accessed 27/09/07)

💊 Interactions

Deferiprone chelates trivalent metal ions and could interact with aluminium-containing preparations; it should not be given with aluminium-containing antacids. Due to the risk of additive toxicity, use with drugs that may cause neutropenia or agranulocytosis is not recommended.

💊 Pharmacokinetics

Deferiprone is rapidly absorbed from the gastrointestinal tract with peak serum concentrations occurring 45 to 60 minutes after an oral dose; absorption may be slowed in the presence of food and peak serum concentrations may be reduced. Deferiprone is metabolised to an inactive glucuronide metabolite and is excreted primarily in the urine, mainly as the metabolite and the irondeferiprone complex, with a small amount of unchanged drug. The elimination half-life is about 2 to 3 hours.

💊 Uses and Administration

Deferiprone is an orally active iron chelator used in the treatment of iron overload in patients with thalassaemia for whom desferrioxamine is unsuitable or ineffective. It may be given by mouth in doses of 25 mg/kg three times daily. Doses above 100 mg/kg daily are not recommended. For use in children, see Administration in Children, below.
1. Barman Balfour JA, Foster RH. Deferiprone: a review of its clinical potential in iron overload in β-thalassaemia major and other transfusion-dependent diseases. Drugs 1999; 58: 553–78
2. Kontoghiorghes GJ, et al. Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Safety 2003; 26: 553–84
3. Hoffbrand AV. Deferiprone therapy for transfusional iron overload. Best Pract Res Clin Haematol 2005; 18: 299–317
4. Piga A, et al. Deferiprone: new insight. Ann N Y Acad Sci 2005; 1054: 169–74.

Administration in children.

UK licensed product information states that there are limited data on the use of deferiprone in children between 6 and 10 years of age, and no data on use in children below 6. Australian licensed product information states that limited data exist for children between the ages of 2 and 10 but that the effects of deferiprone on growth are unknown. Licensed doses in children are calculated by weight on the same basis as adults (see Uses and Administration, above).

Thalassaemia.

Patients with thalassaemia receiving regular blood transfusions commonly develop iron overload requiring use of iron chelators. Deferiprone was developed as an oral alternative to desferrioxamine, but its role has been controversial. See Thalassaemia under Uses of Desferrioxamine, for further information.

💊 Preparations

Proprietary Preparations

Arg.: Ferriprox; Austral.: Ferriprox; Belg.: Ferriprox; Braz.: Ferriprox; Cz.: Ferriprox; Denm.: Ferriprox; Fin.: Ferriprox; Fr.: Ferriprox; Ger.: Ferriprox; Gr.: Ferriprox; Kelfer; Hong Kong: Ferriprox; India: Kelfer; Irl.: Ferriprox†; Ital.: Ferriprox; Malaysia: Ferriprox; Kelfer; Neth.: Ferriprox; Port.: Ferriprox; Spain: Ferriprox; Swed.: Ferriprox; Switz.: Ferriprox; Turk.: Ferriprox; UK: Ferriprox.
Published October 25, 2018.