Myalepta

HOS-097903 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile A total of 148 patients with generalised and partial LD received metreleptin during clinical studies. Safety and efficacy data were analysed in a subgroup of partial LD patients with the following characteristics: 12 years of age and above with leptin levels < 12 ng/mL, TG ≥ 5.65 mmol/L and/or HbA1c ≥ 8%. The adverse reactions reported in generalised LD and this subgroup of partial LD patients are listed in Table 7. Additionally, adverse reactions from post-marketing sources are also presented. The most frequently occurring adverse reactions from the clinical studies were hypoglycaemia (14%) and weight decreased (17%). Tabulated list of adverse reactions Adverse reactions are classified by MedDRA System Organ Class and absolute frequency in Table 7. Frequencies are defined as 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 available data). Due to the number of patients with generalised and partial LD treated in clinical trials, it is not possible to detect with certainty, events which occur at a frequency of < 1%. Table 7 Adverse reactions reported with Myalepta in > 1 patient during clinical studies in generalised LD and the subgroup of partial LD patients and post-marketing experience System Organ Class Very common Common Frequency not known* Infections and infestations Influenza, Pneumonia Immune system disorders Anaphylactic reaction Metabolism and nutrition Hypoglycaemia Decreased appetite Diabetes mellitus, disorders Hyperphagia, Insulin resistance Nervous system disorders Headache Cardiac disorders Tachycardia Vascular disorders Deep vein thrombosis Respiratory, thoracic and Cough, Dyspnoea mediastinal disorders Pleural effusion Gastrointestinal disorders Abdominal pain, Abdominal pain upper,

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HOS-097899 · has-contraindication-information · PDF-Seite 7

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-097898 · has-indication-information · PDF-Seite 2

Myalepta is indicated as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients: • with confirmed congenital generalised LD (Berardinelli-Seip syndrome) or acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above 2 • with confirmed familial partial LD or acquired partial LD (Barraquer-Simons syndrome), in adults and children 12 years of age and above for whom standard treatments have failed to achieve adequate metabolic control.

HOS-097901 · has-interaction-information · PDF-Seite 9

No interaction studies have been performed in humans. Leptin is a cytokine and has the potential to alter the formation of cytochrome P450 (CYP450) enzymes. Since it cannot be excluded that metreleptin may reduce exposure to substrates of CYP3A through enzyme induction, the efficacy of hormonal contraceptives may be reduced if co-administered with metreleptin (see section 4.6). Therefore, an additional non-hormonal contraceptive method should be considered during treatment. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of metreleptin, in patients being treated with these types of agents, therapeutic monitoring of effect (e.g., warfarin), or drug concentrations (e.g. cyclosporin or theophylline) should be performed and the individual dose of the agent adjusted as needed. When starting therapy with Myalepta there is a risk of hypoglycaemia in patients who are on anti-diabetic medicinal products, in particular insulin or insulin secretagogues (see section 4.4).

HOS-097902 · has-pregnancy-information · PDF-Seite 9

Women of childbearing potential Female patients of childbearing potential should be advised to use adequate contraception, if necessary, during treatment with metreleptin. Concomitant administration of Myalepta with hormonal contraceptives may decrease hormonal contraceptives bioavailability (see section 4.5). Women should be counselled to use an alternative non-hormonal method of contraception when Myalepta is used with hormonal contraceptives. Pregnancy Myalepta is not recommended during pregnancy and in women of childbearing potential not using contraception. Abortions, stillbirths and preterm deliveries have been reported in women exposed to metreleptin during pregnancy, though there is currently no evidence to suggest a causal relationship with the treatment. Studies in animals have shown some evidence of reproductive toxicity (see section 5.3). Breast-feeding It is unknown whether metreleptin or its metabolites are excreted in human milk. Endogenous leptin is present in human milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Myalepta therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 9 Fertility There are data to suggest metreleptin may increase fertility, due to effects on LH, with the consequent potential for unplanned pregnancy (see section 4.4). Animal studies showed no adverse effects on male or female fertility (see section 5.3).

HOS-097900 · has-warning-information · PDF-Seite 7

Data from clinical trials do not support safety and efficacy in patients with HIV-related LD. Hypersensitivity reactions There have been reports of generalised hypersensitivity (e.g. anaphylaxis, urticaria or generalised rash) in patients using Myalepta (see section 4.8). Anaphylactic reactions may follow immediately after administration of the medicine. If an anaphylactic reaction or other serious allergic reaction occurs, administration should be permanently discontinued immediately and appropriate therapy initiated. Acute pancreatitis associated with discontinuation of Myalepta Non-compliance with, or abrupt discontinuation of, Myalepta may result in worsening hypertriglyceridaemia and associated pancreatitis, particularly in patients with risk factors for pancreatitis (e.g. history of pancreatitis, severe hypertriglyceridaemia) (see section 4.8). If a patient develops pancreatitis whilst being treated with metreleptin, it is advised that metreleptin be continued uninterrupted, as stopping treatment abruptly may exacerbate the condition. If metreleptin must be stopped for any reason, tapering of the dose over a two-week period is recommended in conjunction with a low fat diet, see section 4.2. During tapering, monitor triglyceride levels and consider initiating or adjusting the dose of lipid-lowering medicinal products as needed. Signs and/or symptoms consistent with pancreatitis should prompt an appropriate clinical evaluation. 7 Hypoglycaemia with concomitant use of insulin and other anti-diabetics There is a risk of hypoglycaemia in patients treated with Myalepta who are on anti-diabetic medicinal products, in particular insulin or insulin secretagogues (e.g. sulphonylureas). Large dose reductions of 50% or more of baseline insulin requirements may be needed in the first 2 weeks of treatment. Once insulin requirements have stabilised, dose adjustments of other anti-diabetics may also be needed in some patients to minimise the risk of hypoglycaemia. Blood glucose in patients on concomitant insulin therapy, especially those on high doses, or insulin secretagogues and combination treatment should be closely monitored. Patients and carers should be advised to be aware of the signs and symptoms of hypoglycaemia. In clinical studies, hypoglycaemia has been managed with food/drink intake and by modifying the dose of anti-diabetic medicinal product. In case of hypoglycaemic events of a non-severe

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