Cystagon · 4.3 Contraindications · 2

HOS-083277 · has-adverse-reaction-information · PDF-Seite 4

Approximately 35% of patients can be expected to experience adverse reactions. These mainly involve the gastrointestinal and central nervous systems. When these effects appear at the initiation of cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in improving tolerance. Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriouness Investigations Common: Liver function tests abnormal Blood and lymphatic system disorders Uncommon: Leukopenia Nervous system disorders Common: Headache, encephalopathy Uncommon: Somnolence, convulsions Gastrointestinal disorders Very common: Vomiting, nausea, diarrhoea Common: Abdominal pain, breath odour, dyspepsia, gastroenteritis Uncommon: Gastrointestinal ulcer Renal and urinary disorders Uncommon: Nephrotic syndrome Skin and subcutaneous tissue disorders Common: Skin odour abnormal, rash Uncommon: Hair colour changes, skin striae, skin fragility (molluscoid pseudotumor on elbows) Musculoskeletal and connective tissue Uncommon: Joint hyperextension, leg pain, genu disorders valgum, osteopenia, compression fracture, scoliosis. Metabolism and nutrition disorders Very common: Anorexia General disorders and administration site Very common: Lethargy, pyrexia conditions Common: Asthenia Immune system disorders Uncommon: Anaphylactic reaction Psychiatric disorders Uncommon: Nervousness, hallucination 4 Cases of nephrotic syndrome have been reported within 6 months of starting therapy with progressive recovery after treatment discontinuation. In some cases, histology showed a membranous glomerulonephritis of the renal allograft and hypersensitivity interstitial nephritis. Cases of Ehlers-Danlos like syndrom

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083283 · has-adverse-reaction-information · PDF-Seite 11

Approximately 35% of patients can be expected to experience adverse reactions. These mainly involve the gastrointestinal and central nervous systems. When these effects appear at the initiation of cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in improving tolerance. Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriouness Investigations Common: Liver function tests abnormal Blood and lymphatic system disorders Uncommon: Leukopenia Nervous system disorders Common: Headache, encephalopathy Uncommon: Somnolence, convulsions Gastrointestinal disorders Very common: Vomiting, nausea, diarrhoea Common: Abdominal pain, breath odour, dyspepsia, gastroenteritis Uncommon: Gastrointestinal ulcer Renal and urinary disorders Uncommon: Nephrotic syndrome Skin and subcutaneous tissue disorders Common: Skin odour abnormal, rash Uncommon: Hair colour changes, skin striae, skin fragility (molluscoid pseudotumor on elbows) Musculoskeletal and connective tissue Uncommon: Joint hyperextension, leg pain, genu disorders valgum, osteopenia, compression fracture, scoliosis. Metabolism and nutrition disorders Very common: Anorexia General disorders and administration site Very common: Lethargy, pyrexia conditions Common: Asthenia Immune system disorders Uncommon: Anaphylactic reaction Psychiatric disorders Uncommon: Nervousness, hallucination 11 Cases of nephrotic syndrome have been reported within 6 months of starting therapy with progressive recovery after treatment discontinuation. In some cases, histology showed a membranous glomerulonephritis of the renal allograft and hypersensitivity interstitial nephritis. Cases of Ehlers-Danlos like syndro

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083279 · has-contraindication-information · PDF-Seite 10

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 The use of CYSTAGON is contra-indicated during breast-feeding. CYSTAGON should not be used during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.6 and section 5.3), as it is teratogenic in animals. CYSTAGON is contraindicated in patients who have developed hypersensitivity to penicillamine.

HOS-083273 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 The use of CYSTAGON is contra-indicated during breast-feeding. CYSTAGON should not be used during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.6 and section 5.3 as it is teratogenic in animals. CYSTAGON is contraindicated in patients who have developed hypersensitivity to penicillamine.

HOS-083272 · has-indication-information · PDF-Seite 2

CYSTAGON is indicated for the treatment of proven nephropathic cystinosis. Cysteamine reduces cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis patients and, when treatment is started early, it delays the development of renal failure.

HOS-083278 · has-indication-information · PDF-Seite 9

CYSTAGON is indicated for the treatment of proven nephropathic cystinosis. Cysteamine reduces cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis patients and, when treatment is started early, it delays the development of renal failure.

HOS-083281 · has-interaction-information · PDF-Seite 10

No interaction studies have been performed Interactions with other medicines have not been studied. CYSTAGON can be administered with electrolyte and mineral replacements necessary for management of the Fanconi syndrome as well as vitamin D and thyroid hormones. Indomethacin and CYSTAGON have been used simultaneously in some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used with cysteamine. 10

HOS-083275 · has-interaction-information · PDF-Seite 3

No interaction studies have been performed CYSTAGON can be administered with electrolyte and mineral replacements necessary for management of the Fanconi syndrome as well as vitamin D and thyroid hormones. Indomethacin and CYSTAGON have been used simultaneously in some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used with cysteamine. 3

HOS-083276 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are no adequate data from the use of cysteamine bitartrate in pregnant women. Studies in animals have shown reproductive toxicity, including teratogenesis (see section 5.3). The potential risk for humans is unknown. The effect on pregnancy of untreated cystinosis is also unknown. Therefore, CYSTAGON should not be used during pregnancy, particularly during the first trimester, unless clearly necessary. If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered and the patient must be advised of the possible teratogenic risk of cysteamine. Breast-feeding CYSTAGON excretion in human's milk is unknown. However, due to the results of animal studies in breast-feeding mothers and neonates (see section 5.3), breast-feeding is contraindicated in women taking CYSTAGON.

HOS-083282 · has-pregnancy-information · PDF-Seite 11

Pregnancy There are no adequate data from the use of cysteamine bitartrate in pregnant women. Studies in animals have shown reproductive toxicity, including teratogenesis (see section 5.3). The potential risk for humans is unknown. The effect on pregnancy of untreated cystinosis is also unknown. Therefore, CYSTAGON should not be used during pregnancy, particularly during the first trimester, unless clearly necessary. If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered and the patient must be advised of the possible teratogenic risk of cysteamine. Breast-feeding CYSTAGON excretion in human's milk is unknown. However, due to the results of animal studies in breast-feeding mothers and neonates (see section 5.3), breast-feeding is contra-indicated in women taking CYSTAGON.

HOS-083274 · has-warning-information · PDF-Seite 3

CYSTAGON therapy must be initiated promptly after confirmation of the diagnosis of nephropathic cystinosis to achieve maximum benefit. Nephropathic cystinosis must have been diagnosed by both clinical signs and biochemical investigations (leucocyte cystine measurements). Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in children treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. These skin lesions were associated with vascular proliferation, skin striae and bone lesions. It is therefore recommended to monitor regularly skin and to consider X-ray examinations of the bone as necessary. Self-examination of the skin by the patient or the parents should also be advised. If any similar skin or bone abnormalities appear, it is recommended to decrease the dose of CYSTAGON. The use of doses higher than 1.95g/m2/day is not recommended (see sections 4.2 and 4.8). Monitoring of blood cell count is recommended on a regular basis. Oral cysteamine has not been shown to prevent eye deposition of cystine crystals. Therefore, where cysteamine ophthalmic solution is used for that purpose, its usage should continue. In contrast to phosphocysteamine, CYSTAGON does not contain phosphate. Most patients will already be receiving phosphate supplements and the dose of these may need to be altered when CYSTAGON is substituted for phosphocysteamine. Intact CYSTAGON hard capsules should not be administered to children under the age of approximately 6 years due to risk of aspiration (see section 4.2). Do not swallow the desiccant canister found in the bottle

HOS-083280 · has-warning-information · PDF-Seite 10

CYSTAGON therapy must be initiated promptly after confirmation of the diagnosis of nephropathic cystinosis to achieve maximum benefit. Nephropathic cystinosis must have been diagnosed by both clinical signs and biochemical investigations (leucocyte cystine measurements). Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in children treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. These skin lesions were associated with vascular proliferation, skin striae and bone lesions. It is therefore recommended to monitor regularly skin and to consider X-ray examinations of the bone as necessary. Self-examination of the skin by the patient or the parents should also be advised. If any similar skin or bone abnormalities appear, it is recommended to decrease the dose of CYSTAGON. The use of doses higher than 1.95g/m2/day is not recommended (see sections 4.2 and 4.8). Monitoring of blood cell count is recommended on a regular basis. Oral cysteamine has not been shown to prevent eye deposition of cystine crystals. Therefore, where cysteamine ophthalmic solution is used for that purpose, its usage should continue. In contrast to phosphocysteamine, CYSTAGON does not contain phosphate. Most patients will already be receiving phosphate supplements and the dose of these may need to be altered when CYSTAGON is substituted for phosphocysteamine. Intact CYSTAGON hard capsules should not be administered to children under the age of approximately 6 years due to risk of aspiration (see section 4.2). Do not swallow the desiccant canister found in the bottle.