Leitlinien & Arzneimittelsicherheit

HOS-155511 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile For the immediate-release formulation of cysteamine bitartrate, approximately 35% of patients can be expected to experience adverse reactions. These mainly involve the gastrointestinal and central nervous systems. When these reactions appear at the initiation of cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in improving tolerance. In clinical studies with healthy volunteers, the most frequent adverse reactions were very common GI symptoms (16%) and occurred primarily as single episodes that were mild or moderate in severity. The adverse reactions profile for healthy subjects was similar to the adverse reactions profile in patients relative to GI disorders (diarrhoea and abdominal pain). Tabulated list of adverse reactions The frequency of adverse reactions is defined using the following convention: 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) and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: Table 2: Adverse reactions MedDRA system organ class Frequency: adverse reaction Blood and lymphatic system disorders Uncommon: Leukopenia Immune system disorders Uncommon: Anaphylactic reaction Metabolism and nutrition disorders Very common: Anorexia Psychiatric disorders Uncommon: Nervousness, hallucination Common: Headache, encephalopathy Nervous system disorders Uncommon: Somnolence, convulsions Very common: Vomiting, nausea, diarrhoea Common: Abdominal pain, breath odour, dyspepsia, Gastrointestinal disorders gastroenteritis Uncommon: Gastrointestinal ulcer Common: Skin odour abnormal, rash Skin and subcutaneous tissue disorders Uncommon: Hair colour changes, skin striae, skin fragility (molluscoid pseudotumour on elbows) Musculoskeletal and connective tissue Uncommon: Joint hyperextension, leg pain, genu disorders val

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HOS-155507 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substance, any form of cysteamine (mercaptamine), or to any of the excipients listed in section 6.1. • Hypersensitivity to penicillamine. • Breast-feeding.

HOS-155506 · has-indication-information · PDF-Seite 2

PROCYSBI 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-155509 · has-interaction-information · PDF-Seite 6

It cannot be excluded that cysteamine is a clinically relevant inducer of CYP enzymes, inhibitor of P-gp and BCRP at the intestinal level and inhibitor of liver uptake transporters (OATP1B1, OATP1B3 and OCT1). Co-administration with electrolyte and mineral replacement Cysteamine can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi syndrome as well as vitamin D and thyroid hormone. Bicarbonate should be administered at least one hour before or one hour after PROCYSBI to avoid potential earlier release of cysteamine. Indomethacin and cysteamine have been used simultaneously in some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used with cysteamine. Co-administration of the proton pump inhibitor omeprazole and PROCYSBI in vivo showed no effects on cysteamine bitartrate exposure.

HOS-155510 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential Women of childbearing potential should be informed about the risk of teratogenicity and advised to use an adequate method of contraception during the course of treatment. A negative pregnancy test should be confirmed before starting treatment. Pregnancy There is no adequate data from the use of cysteamine 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, cysteamine bitartrate should not be used during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.4). If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered. Breast-feeding Cysteamine excretion in human milk is unknown. However, due to the results of animal studies in breast-feeding females and neonates (see section 5.3), breast-feeding is contra-indicated in women taking PROCYSBI (see section 4.3). Fertility Effects on fertility have been seen in animal studies (see section 5.3). Azoospermia has been reported in male cystinosis patients.

HOS-155508 · has-warning-information · PDF-Seite 4

The use of doses higher than 1.95 g/m2/day is not recommended (see section 4.2). 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. 4 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 (see section 4.6). Intact capsules of PROCYSBI should not be administered to children under the age of approximately 6 years due to risk of aspiration (see section 4.2). Dermatological There have been reports of serious skin lesions in patients treated with high doses of immediate- release cysteamine bitartrate or other cysteamine salts that have responded to cysteamine dose reduction. Physicians should routinely monitor the skin and bones of patients receiving cysteamine. If skin or bone abnormalities appear, the dose of cysteamine should be reduced or stopped. Treatment may be restarted at a lower dose under close supervision, and then slowly titrated to the appropriate therapeutic dose (see sections 4.2). If a severe skin rash develops such as erythema multiforme bullosa or toxic epidermal necrolysis, cysteamine should not be re-administered (see sections 4.8). Gastrointestinal GI ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. Physicians should remain alert for signs of ulceration and bleeding and should inform patients and/or guardians about the signs and symptoms of serious GI toxicity and what steps to take if they occur. GI tract symptoms including nausea, vomiting, anorexia and abdominal pain have been associated with cysteamine. Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) was first described in cystic fibrosis patients who were given high doses of pancreatic enzymes in the form of tablets with an enteric coating of methacrylic acid - ethyl acrylate copolymer (1:1), one of the excipients in PROCYSBI. As a precaution, unusual abdominal symptoms or changes in abdominal symptoms should be medically assessed to exclude the possibility of fibrosing colonopathy. Central Nervous System (CNS) CNS symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with cysteamine. If CNS symptoms develop, the patient should be carefully evaluated and the

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