Myalepta

Treatment should be initiated and monitored by a healthcare professional experienced in the diagnosis and management of metabolic disorders. Posology The recommended daily dose of metreleptin is based on body weight as provided in Table 1.

In order to ensure patients and carers understand the correct dose to be injected, the prescriber should prescribe the appropriate dose both in milligrams and the volume in millilitres. In order to avoid medication errors including overdose, dose calculation and dose adjustment guidelines below should be followed.

A review of the patient’s self-administration technique is recommended every 6 months whilst using Myalepta. Actual body weight at initiation of treatment should always be used when calculating the dose. g. g. tolerability issues, excessive weight loss especially in paediatric patients), the dose may be decreased, or increased to the maximum dose listed in Table 1.

The maximum tolerated dose may be less than the maximum daily dose, outlined in Table 1, as evidenced by excessive weight loss, even if metabolic response is incomplete. 5% HbA1c reduction and/or 25% reduction in insulin requirements and/or • 15% reduction in triglycerides (TGs) If clinical response is not seen after 6 months of treatment the physician should ensure that the patient is compliant with the administration technique, is receiving the correct dose and is adherent to diet.

A dose increase before stopping treatment should be considered. Metreleptin dose increases in adults and children based on incomplete clinical response can be considered after a minimum of 6 months of treatment, allowing for lowering concomitant insulin, oral anti-diabetic and/or lipid lowering medication.

Reductions in HbA1c and TG may not be seen in children as metabolic abnormalities may not be present at the start of treatment. It is anticipated that most children will require increasing per kg dose, especially as they reach puberty.

Increasing abnormalities of TG and HbA1c may be seen which may 4 require a dose increase. Dose adjustments in children without metabolic abnormalities should primarily be made according to weight change. Dose increases should not be made more frequently than every 4 weeks.

Dose decreases based on weight loss may be made weekly. There is a risk of hypoglycaemia in patients treated with Myalepta who are on anti-diabetic therapy. Large dose reductions of 50% or more of baseline insulin requirements may be needed in the initial phases of treatment.

Summary of the safety profile A total of 148 patients with generalised and partial LD received metreleptin during clinical studies. 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 disorders Hypoglycaemia Decreased appetite Diabetes mellitus, Hyperphagia, Insulin resistance Nervous system disorders Headache Cardiac disorders Tachycardia Vascular disorders Deep vein thrombosis Respiratory, thoracic and mediastinal disorders Cough, Dyspnoea Pleural effusion Gastrointestinal disorders Abdominal pain, Nausea Abdominal pain upper, Diarrhoea, Pancreatitis, Vomiting Skin and subcutaneous tissue disorders Alopecia Pruritus, Rash, Urticaria Musculoskeletal and connective tissue disorders Arthralgia, Myalgia Reproductive system and breast disorders Menorrhagia 11 System Organ Class Very common Common Frequency not known* General disorders and administration site conditions Fatigue, Injection site bruising, Injection site erythema, Injection site reaction Fat tissue increased, Injection site haemorrhage, Injection site pain, Injection site pruritus, Injection site swelling, Malaise, Peripheral swelling Investigations Weight decreased Neutralising antibodies Blood glucose abnormal, Blood triglycerides increased, Drug specific antibody present, Glycosylated haemoglobin increased, Weight increased *Global post marketing experience Description of selected adverse reactions 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.

Data from clinical trials do not support safety and efficacy in patients with HIV-related LD. g. 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.

g. 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. 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. 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 nature, food intake management may be considered as an alternative to dose-adjustment of anti-diabetics according to the treating physician’s opinion.

Rotation of injection sites is recommended in patients co-administering insulin (or other subcutaneous medicinal products) and Myalepta. 8) have been reported while using metreleptin in clinical studies. A causal relationship between the medicinal product treatment and the development and/or progression of lymphoma has not been established.

1.