Deferiprone Lipomed · 4.4 Special warnings and precautions for use · 1

HOS-287321 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most common adverse reactions reported during therapy with deferiprone in clinical trials were nausea, vomiting, abdominal pain, and chromaturia, which were reported in more than 10% of patients. The most serious adverse reaction reported in clinical trials with deferiprone was agranulocytosis, defined as an absolute neutrophil count less than 0.5 x 109/l, which occurred in approximately 1% of patients. Less severe episodes of neutropenia were reported in approximately 5% of patients. 6 Tabulated list of adverse reactions The adverse reactions are listed below by system organ class (SOC) and by frequency, with the following frequency grouping: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. System organ class Very common Common Frequency not known Blood and lymphatic system Agranulocytosis disorders Neutropenia Immune system disorders Hypersensitivity reactions Metabolism and nutrition Increased appetite disorders Nervous system disorders Headache Gastrointestinal disorders Vomiting Diarrhoea Nausea Abdominal pain Skin and subcutaneous tissue Rash disorders Urticaria Musculoskeletal and Arthralgia connective tissue disorders Renal and urinary disorders Chromaturia General disorders and Fatigue administration site conditions Investigations Increased liver enzymes Description of selected adverse reactions The most serious adverse reactio

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HOS-287317 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • History of recurrent episodes of neutropenia. • History of agranulocytosis. • Pregnancy (see section 4.6). • Breast-feeding (see section 4.6). • Due to the unknown mechanism of deferiprone-induced neutropenia, patients must not take medicinal products known to be associated with neutropenia or those that can cause agranulocytosis (see section 4.5). 3

HOS-287316 · has-indication-information · PDF-Seite 2

Deferiprone Lipomed monotherapy is indicated for the treatment of iron overload in patients with thalassaemia major when current chelation therapy is contraindicated or inadequate. Deferiprone Lipomed in combination with another chelator (see section 4.4) is indicated in patients with thalassaemia major when monotherapy with any iron chelator is ineffective, or when prevention or treatment of life-threatening consequences of iron overload (mainly cardiac overload) justifies rapid or intensive correction (see section 4.2).

HOS-287319 · has-interaction-information · PDF-Seite 5

Due to the unknown mechanism of deferiprone-induced neutropenia, patients must not take medicinal products known to be associated with neutropenia or those that can cause agranulocytosis (see section 4.3). 5 Since deferiprone binds to metallic cations, the potential exists for interactions between deferiprone and trivalent cation-dependent medicinal products such as aluminium-based antacids. Therefore, it is not recommended to concomitantly ingest aluminium-based antacids and deferiprone. The safety of concurrent use of deferiprone and vitamin C has not been formally studied. Based on the reported adverse interaction that can occur between deferoxamine and vitamin C, caution should be used when administering deferiprone and vitamin C concurrently.

HOS-287320 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential/contraception in men and women Due to the genotoxic potential of deferiprone (see section 5.3), women of childbearing potential are recommended to use effective contraceptive measures and avoid becoming pregnant while being treated with Deferiprone Lipomed and for 6 months following the completion of treatment. Men are recommended to use effective contraceptive measures and to not father a child while receiving Deferiprone Lipomed and for 3 months following completion of treatment. Pregnancy There are no adequate data from the use of deferiprone in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Pregnant women must be advised to immediately stop taking deferiprone (see section 4.3). Breast-feeding It is not known whether deferiprone is excreted in human milk. No prenatal and postnatal reproductive studies have been conducted in animals. Deferiprone must not be used by breast-feeding mothers. If treatment is unavoidable, breast-feeding must be stopped (see section 4.3). Fertility No effects on fertility or early embryonic development were noted in animals (see section 5.3).

HOS-287318 · has-warning-information · PDF-Seite 4

Neutropenia/Agranulocytosis Deferiprone has been shown to cause neutropenia, including agranulocytosis (see section 4.8 ‘Description of selected adverse reactions’). The patient’s absolute neutrophil count (ANC) should be monitored every week during the first year of therapy. For patients whose deferiprone has not been interrupted during the first year of therapy due to any decrease in the neutrophil count, the frequency of ANC monitoring may be extended to the patient’s blood transfusion interval (every 2 – 4 weeks) after one year of deferiprone therapy. The change from weekly ANC monitoring, to monitoring at the time of transfusion visits after 12 months of deferiprone therapy should be considered on an individual patient basis, according to the physician’s assessment of the patient’s understanding of the risk minimization measures required during therapy (see section 4.4 below). In clinical trials, weekly monitoring of the neutrophil count has been effective in identifying cases of neutropenia and agranulocytosis. Agranulocytosis and neutropenia usually resolve upon discontinuation of deferiprone, but fatal cases of agranulocytosis have been reported. If the patient develops an infection while on deferiprone, therapy should be immediately interrupted, and an ANC obtained without delay. The neutrophil count should then be monitored more frequently. Patients should be aware to contact their physician if they experience any symptoms indicative of infection (such as fever, sore throat and flu-like symptoms). Immediately interrupt deferiprone if the patient experiences infection. Suggested management of cases of neutropenia is outlined below. It is recommended that such a management protocol be in place prior to initiating any patient on deferiprone treatment. Treatment with deferiprone should not be initiated if the patient is neutropenic. The risk of agranulocytosis and neutropenia is higher if the baseline ANC is less than 1.5 x 109/l. For neutropenia events (ANC < 1.5 x 109/l and > 0.5 x 109/l) Instruct the patient to immediately discontinue deferiprone and all other medicinal products with a potential to cause neutropenia. The patient should be advised to limit contact with other individuals in order to reduce the risk of infection. Obtain a complete blood cell (CBC) count, with a white blood cell (WBC) count, corrected for the presence of nucleated red blood cells, a neutrophil count, and a platelet count immediately upon diagnosing the event a

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