Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.3 · PDF-Seite 7

HOS-136638 · Präparat HOS-097896

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

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Wechselwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.5 · PDF-Seite 9

HOS-136639 · Präparat HOS-097896

No interaction studies have been performed in humans.

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Wechselwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.5 · PDF-Seite 9

HOS-136640 · Präparat HOS-097896

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).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): theophylline (HOS-085910) leptin (HOS-136641) warfarin (HOS-085950)

Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136642 · Präparat HOS-097896

Summary of the safety profile

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136643 · Präparat HOS-097896

A total of 148 patients with generalised and partial LD received metreleptin during clinical studies.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136644 · Präparat HOS-097896

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%.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136645 · Präparat HOS-097896

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%).

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136646 · Präparat HOS-097896

Tabulated list of adverse reactions

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136647 · Präparat HOS-097896

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%.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10

HOS-136648 · Präparat HOS-097896

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, Nausea Diarrhoea, Pancreatitis, Vomiting Skin and subcutaneous tissue Alopecia Pruritus, Rash, Urticaria disorders Musculoskeletal and Arthralgia, Myalgia connective tissue disorders Reproductive system and Menorrhagia breast disorders

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 10–11

HOS-136649 · Präparat HOS-097896

10  System Organ Class Very common Common Frequency not known* General disorders and Fatigue, Injection Fat tissue increased, administration site conditions site bruising, Injection site Injection site haemorrhage, Injection erythema, Injection site pain, Injection site site reaction pruritus, Injection site swelling, Malaise, Peripheral swelling Investigations Weight Neutralising Blood glucose abnormal, decreased antibodies Blood triglycerides increased, Drug specific antibody present, Glycosylated haemoglobin increased, Weight increased *Global post marketing experience

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11

HOS-136650 · Präparat HOS-097896

Description of selected adverse reactions

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11

HOS-136651 · Präparat HOS-097896

Acute pancreatitis associated with discontinuation of metreleptin In clinical studies, 6 patients (4 with generalised LD and 2 with partial LD), experienced treatment-emergent pancreatitis. All patients had a history of pancreatitis and hypertriglyceridaemia. Abrupt interruption and/or non-compliance with metreleptin dosing was suspected to have contributed to the occurrence of pancreatitis in 2 patients. The mechanism for pancreatitis in these patients was presumed to be return of hypertriglyceridaemia and therefore increased risk of pancreatitis in the setting of discontinuation of effective therapy for hypertriglyceridaemia.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11

HOS-136652 · Präparat HOS-097896

Hypoglycaemia Metreleptin may decrease insulin resistance in diabetic patients, resulting in hypoglycaemia in patients with LD and co-existing diabetes. Hypoglycaemia, deemed as related to metreleptin treatment, occurred in 14.2% of patients studied. All reports of hypoglycaemia in patients with generalised LD and in the subgroup of partial LD patients, have been mild in nature with no pattern of onset or clinical sequelae. Generally the majority of events could be managed by food intake with only relatively few modifications of anti-diabetic medicinal product dose occurring.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11

HOS-136653 · Präparat HOS-097896

T-cell lymphoma Three cases of T-cell lymphoma have been reported while using metreleptin in clinical studies. All three patients had acquired generalised LD. Two of these patients were diagnosed with peripheral T-cell lymphoma while receiving the medicinal product. Both had immunodeficiency and significant haematological abnormalities including severe bone marrow abnormalities before the start of treatment. A separate case of anaplastic large cell lymphoma was reported in a paediatric patient receiving the medicinal product who did not have haematological abnormalities before treatment.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11

HOS-136654 · Präparat HOS-097896

Immunogenicity In clinical trials (Studies NIH 991265/20010769 and FHA101), the rate of ADAs for generalised LD and the partial LD patients studied and with data available were 88% (65 out of 74 patients). A blocking activity of the reaction between metreleptin and a recombinant leptin receptor has been observed in vitro in the blood of the majority of an extended set of patients (98 out of 102 patients or 96%) but the impact on the efficacy of metreleptin could not be clearly established. Serious and/or severe infections that were temporally associated with > 80% blocking activity against metreleptin occurred in 5 generalised LD patients. These events included 1 episode in 1 patient of serious and severe appendicitis, 2 episodes in patients of serious and severe pneumonia, a single episode of serious and severe sepsis and non-serious severe gingivitis in 1 patient and 6 episodes of serious and severe sepsis or bacteraemia and 1 episode of non-serious severe ear infection in 1 patient. One serious and severe infection of appendicitis was temporally associated with blocking activity against metreleptin in a patient with partial LD who was not in the subgroup of partial LD patients. Though temporally associated, it is not possible to unequivocally confirm or deny a direct relation to

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 11–12

HOS-136655 · Präparat HOS-097896

11 metreleptin treatment based on the currently available body of evidence. LD patients with a blocking activity against metreleptin and concurrent infections responded to standard of care treatment (see section 4.4).

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 12

HOS-136656 · Präparat HOS-097896

Injection site reactions Injection site reactions were reported in 3.4% of patients with LD treated with metreleptin. All events reported in clinical studies in patients with LD have been mild or moderate in severity and none have led to treatment discontinuation. Most events occurred during the initial 1-2 months of initiation of treatment.

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 12

HOS-136657 · Präparat HOS-097896

Paediatric population

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Nebenwirkungen · Myalepta

Myalepta 3 mg powder for solution for injection. Myalepta 5.8 mg powder for solution for injection. Myalepta 11.3 mg powder for solution for injection. · Abschnitt 4.8 · PDF-Seite 12

HOS-136658 · Präparat HOS-097896

Across two completed clinical studies (NIH 991265/20010769 and FHA101), there were 52 paediatric patients (4 in the subgroup of partial LD patients and 48 with generalised LD) enrolled and exposed to metreleptin. Limited clinical data exists in children less than 2 years old for generalised LD patients and less than 12 years old in partial LD patients.

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