Ferriprox · 4.1 Therapeutic indications · 1

HOS-083940 · has-adverse-reaction-information · PDF-Seite 20

Summary of the safety profile The most common adverse reactions reported during therapy with deferiprone in clinical studies were nausea, vomiting, abdominal pain, and chromaturia, which were reported in more than 10% of patients. The most serious adverse reaction reported in clinical studies with deferiprone was agranulocytosis, defined as an absolute neutrophil count less than 0.5x109/l, which occurred in approximately 1% of patients. Less severe episodes of neutropenia were reported in approximately 5% of patients. Tabulated list of adverse reactions Adverse reaction frequencies: very common (≥ 1/10), common (≥ 1/100 to < 1/10), not known (cannot be estimated from the available data). Table 2: List of adverse reactions System organ class Very common Common Frequency not (≥ 1/10) (≥ 1/100 to < 1/10) known Blood and lymphatic system Neutropenia disorders Agranulocytosis Immune system disorders Hypersensitivity reactions Metabolism and nutrition Increased appetite disorders Nervous system disorders Headache Gastrointestinal disorders Nausea Diarrhoea Abdominal pain Vomiting 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 reaction reported in clinical studies with deferiprone is agranulocytosis (neutrophils < 0.5x109/l), with an incidence of 1.1% (0.6 cases per 100 patient-years of treatment) (see section 4.4). Data from pooled clinical studies in patients with systemic iron overload showed that 63% of the episodes of agranulocytosis occu

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HOS-083934 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most common adverse reactions reported during therapy with deferiprone in clinical studies were nausea, vomiting, abdominal pain, and chromaturia, which were reported in more than 10% of patients. The most serious adverse reaction reported in clinical studies with deferiprone was agranulocytosis, defined as an absolute neutrophil count less than 0.5x109/l, which occurred in approximately 1% of patients. Less severe episodes of neutropenia were reported in approximately 5% of patients. Tabulated list of adverse reactions Adverse reaction frequencies: very common (≥ 1/10), common (≥ 1/100 to < 1/10), not known (cannot be estimated from the available data). Table 2: List of adverse reactions System organ class Very common Common Frequency not (≥ 1/10) (≥ 1/100 to < 1/10) known Blood and lymphatic system Neutropenia disorders Agranulocytosis Immune system disorders Hypersensitivity reactions Metabolism and nutrition Increased appetite disorders Nervous system disorders Headache Gastrointestinal disorders Nausea Diarrhoea Abdominal pain Vomiting 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 7 Description of selected adverse reactions The most serious adverse reaction reported in clinical studies with deferiprone is agranulocytosis (neutrophils < 0.5x109/l), with an incidence of 1.1% (0.6 cases per 100 patient-years of treatment) (see section 4.4). Data from pooled clinical studies in patients with systemic iron overl

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HOS-083936 · has-contraindication-information · PDF-Seite 17

- 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).

HOS-083930 · has-contraindication-information · PDF-Seite 4

- 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).

HOS-083935 · has-indication-information · PDF-Seite 15

Ferriprox monotherapy is indicated for the treatment of iron overload in patients with thalassaemia major when current chelation therapy is contraindicated or inadequate. Ferriprox 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-083929 · has-indication-information · PDF-Seite 2

Ferriprox monotherapy is indicated for the treatment of iron overload in patients with thalassaemia major when current chelation therapy is contraindicated or inadequate. Ferriprox 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-083938 · has-interaction-information · PDF-Seite 19

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). 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-083932 · has-interaction-information · PDF-Seite 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 4.3). 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-083939 · has-pregnancy-information · PDF-Seite 19

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 use effective contraceptive measures and avoid becoming pregnant while being treated with Ferriprox 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 Ferriprox 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-083933 · 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 Ferriprox 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 Ferriprox 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). 6 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-083937 · has-warning-information · PDF-Seite 17

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 Ferriprox 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 Ferriprox 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 studies, weekly monitoring of the neutrophil count has been effective in identifying cases of neutropenia and agranulocytosis. Agranulocytosis and neutropenia usually resolve upon discontinuation of Ferriprox, 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 be then 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 1.5x109/l. For neutropenia events (ANC < 1.5x109/l and > 0.5x109/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 and then repe

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HOS-083931 · 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 Ferriprox 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 Ferriprox 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 studies, weekly monitoring of the neutrophil count has been effective in identifying cases of neutropenia and agranulocytosis. Agranulocytosis and neutropenia usually resolve upon discontinuation of Ferriprox, 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 be then 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. 4 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 1.5x109/l. For neutropenia events (ANC < 1.5x109/l and > 0.5x109/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 co

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