title: Safety profile of the oral iron chelator deferiprone: a multicentre study.
abstract: In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA, USA; Istituto di Clinica e Biologia Dell'Eta'Evolutiva, Cagliari, Italy. cohen@email.chop.edu
authors.forename: A R
authors.initials: AR
authors.lastname: Cohen
authors.forename: R
authors.initials: R
authors.lastname: Galanello
authors.forename: A
authors.initials: A
authors.lastname: Piga
authors.forename: A
authors.initials: A
authors.lastname: Dipalma
authors.forename: C
authors.initials: C
authors.lastname: Vullo
authors.forename: F
authors.initials: F
authors.lastname: Tricta
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced; D000410:Alanine Transaminase / Q000378:metabolism; D000077543:Deferiprone; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects*; D007592:Joint Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D011446:Prospective Studies; D011728:Pyridones / Q000009:adverse effects*; D016896:Treatment Outcome; D015032:Zinc / Q000378:metabolism; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000652:urine
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D000410:Alanine Transaminase; D015032:Zinc