Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Amryt Pharmaceuticals DAC, 45 Mespil Road, Dublin 4, Ireland
Myalepta is indicated as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients:
Treatment should be initiated and monitored by a healthcare professional experienced in the diagnosis and management of metabolic disorders.
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.
Table 1. Metreleptin recommended dose:
| Baseline weight | Starting daily dose (injection volume) | Dose adjustments (injection volume) | Maximum daily dose (injection volume) |
|---|---|---|---|
| Males and females ≤40 kg | 0.06 mg/kg (0.012 mL/kg) | 0.02 mg/kg (0.004 mL/kg) | 0.13 mg/kg (0.026 mL/kg) |
| Males >40 kg | 2.5 mg (0.5 mL) | 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) | 10 mg (2 mL) |
| Females >40 kg | 5 mg (1 mL) | 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) | 10 mg (2 mL) |
Based on clinical response (e.g. inadequate metabolic control) or other consideration (e.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.
A minimum clinical response is defined as at least:
and / or
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. Consider dose increase before stopping treatment.
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 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. Once insulin requirements have stabilised, dose adjustments of other anti-diabetic therapies may also be needed in some patients to minimise the risk of hypoglycaemia (see section 4.4 and 4.8).
When discontinuing Myalepta in patients with risk factors for pancreatitis (e.g. history of pancreatitis, severe hypertriglyceridaemia), tapering of the dose over a two-week period is recommended in conjunction with a low-fat diet. 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 (see section 4.4).
If a patient misses a dose, the dose should be administered as soon as the omission is noticed and the normal dosing schedule resumed the next day.
Clinical trials of metreleptin did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. In general, dose selection and modification for an elderly patient should be cautious, although no specific dose adjustment is recommended.
Metreleptin has not been studied in patients with impaired renal or hepatic function. No dose recommendations can be made.
The safety and efficacy of metreleptin in children aged 0 to 2 years with generalised LD and children aged 0 to 12 years with partial LD has not been established. Very limited data are available for children, especially less than 6 years, with generalised LD.
Subcutaneous use.
Healthcare professionals should provide patients and carers with training on the reconstitution of the product and proper subcutaneous injection technique, so as to avoid intramuscular injection in patients with minimal subcutaneous adipose tissue.
Patients and/or carers should prepare and administer the first dose of the medicinal product under the supervision of a qualified healthcare professional.
The injection should be administered at the same time every day. It can be administered any time of the day without regard to the timing of meals.
The reconstituted solution should be injected into the abdomen, thigh or upper arm tissue. It is recommended that patients should use a different injection site each day when injecting in the same region. Doses exceeding 1 mL can be administered as two injections (the total daily dose divided equally) to minimise potential injection site discomfort due to injection volume. When dividing doses due to volume, doses can be administered one after the other at different injection sites.
When small doses/volumes are prescribed (e.g. in children), the vials will remain almost completely filled with product after withdrawal of the required dose. Remaining reconstituted product should be discarded after use.
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and the information intended for patients in the package leaflet (section 7).
Table 2. Dose calculation:
| Weight and gender | Starting dose calculation |
|---|---|
| For males and females ≤40 kg once daily dose | Weight (kg) x 0.06 mg/kg = Individual patient daily starting dose in mg Weight (kg) x 0.012 mL/kg = Individual patient daily starting volume to inject in mL Example: 25 kg patient is initiated at 0.06 mg/kg of Myalepta. The individual patient dose = 1.5 mg 25 kg patient is initiated at 0.012 mL/kg = 0.3 mL of Myalepta solution to inject |
| For males >40 kg once daily dose | Individual patient once daily dose in mg = 2.5 mg Amount to inject once daily dose = 0.5 mL |
| For females >40 kg once daily dose | Individual patient once daily dose in mg = 5 mg Amount to inject once daily dose = 1 mL |
Table 3. Required syringe for Myalepta reconstitution with water for injection:
| Syringe | Needle gauge and length |
|---|---|
| Myalepta 3 mg powder for solution for injection | |
| 1.0 mL | 21 gauge 40 mm needle |
| Myalepta 5.8 mg powder for solution for injection | |
| 3.0 mL | 21 gauge 40 mm needle |
| Myalepta 11.3 mg powder for solution for injection | |
| 3.0 mL | 21 gauge 40 mm needle |
Table 4. Required administration syringe per Myalepta dose:
| Syringe | Needle gauge and length | Myalepta dose range to be administered |
|---|---|---|
| 0.3 mL U100 Insulin Syringe | 31 gauge 8 mm needle | For doses of: |
| 1.0 mL | 30 gauge 13 mm needle | For doses of: >1.5 mg – 5 mg / 0.3 – 1.0 mL volume daily |
| 2.5 mL | 30 gauge 13 mm needle | For doses of: >5 mg – 10 mg / >1.0 mL volume daily |
For patients weighing less than 40 kg, actual body weight at initiation of therapy should be used to calculate dose; of these, in patients weighing less than or equal to 25 kg, refer to Table 5 for the starting dose.
Table 5. Conversion table for the 0.3 mL U100 insulin syringe:
| Weight of child | Dose of Myalepta | Actual amount of solution* | Rounded amount of solution | ‘Unit’ measurement volume in 0.3 mL syringe to inject |
|---|---|---|---|---|
| 9 kg | 0.54 mg | 0.108 mL | 0.10 mL | 10 |
| 10 kg | 0.60 mg | 0.120 mL | 0.12 mL | 12 |
| 11 kg | 0.66 mg | 0.132 mL | 0.13 mL | 13 |
| 12 kg | 0.72 mg | 0.144 mL | 0.14 mL | 14 |
| 13 kg | 0.78 mg | 0.156 mL | 0.15 mL | 15 |
| 14 kg | 0.84 mg | 0.168 mL | 0.16 mL | 16 |
| 15 kg | 0.90 mg | 0.180 mL | 0.18 mL | 18 |
| 16 kg | 0.96 mg | 0.192 mL | 0.19 mL | 19 |
| 17 kg | 1.02 mg | 0.204 mL | 0.20 mL | 20 |
| 18 kg | 1.08 mg | 0.216 mL | 0.21 mL | 21 |
| 19 kg | 1.14 mg | 0.228 mL | 0.22 mL | 22 |
| 20 kg | 1.20 mg | 0.240 mL | 0.24 mL | 24 |
| 21 kg | 1.26 mg | 0.252 mL | 0.25 mL | 25 |
| 22 kg | 1.32 mg | 0.264 mL | 0.26 mL | 26 |
| 23 kg | 1.38 mg | 0.276 mL | 0.27 mL | 27 |
| 24 kg | 1.44 mg | 0.288 mL | 0.28 mL | 28 |
| 25 kg | 1.50 mg | 0.300 mL | 0.30 mL | 30 |
* Note: Initial and dose increments should be rounded down to the nearest 0.01 mL
The once daily dose of Myalepta can be increased by increments as shown in Table 6 to a maximum daily dose.
Table 6. Dose adjustment calculation:
| Adjust dose as follows (if necessary) | Action |
|---|---|
| Males and females ≤40 kg | Weight (kg) x 0.02 mg/kg = amount of dose adjustment in mg Example: A 15 kg patient is initiated at 0.06 mg/kg of Myalepta. The individual patient dose = 0.9 mg. A dose increment of 0.02 mg/kg increases the daily dose to 0.08 mg/kg = 1.2 mg. Total daily volume to be injected is total dose in mg/5, in this case it is 1.2 mg/5 = 0.24 mL which equals 24 units on the 0.3 mL insulin syringe. |
| Both males and females >40 kg | For all patients weighing more than 40 kg an incremental adjustment increase in daily dose would be 1.25 mg or 0.25 mL injection volume. Total daily volume to be injected is total dose in mg/5. Example: A male patient is initiated at 2.5 mg of Myalepta daily. A dose increment of 1.25 mg increases the daily dose to 3.75 mg. Total daily volume to be injected is 3.75 mg/5 = 0.75 mL. The maximum daily dose in males and females is 10 mg or 2 mL injection volume |
In one post-marketing case, an infant was exposed to a 10-fold overdose of metreleptin for 8 months. In this case, prolonged overdose was associated with severe anorexia causing vitamin and zinc deficiencies, iron deficiency anaemia, protein calorie malnutrition, and poor weight gain, which resolved following supportive treatment and dose adjustment.
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions and supportive treatment initiated.
3 years.
Following reconstitution with water for injections, the medicinal product must be used immediately and cannot be stored for future use.
Store in a refrigerator (2°C-8°C). Keep the vial in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Myalepta 3 mg powder for solution for injection: Type I glass vial (3 mL) with a chlorobutyl rubber stopper and an aluminium seal/red plastic flip-off cap.
Myalepta 5.8 mg powder for solution for injection: Type I glass vial (3 mL) with a chlorobutyl rubber stopper and an aluminium seal/blue plastic flip-off cap.
Myalepta 11.3 mg powder for solution for injection: Type I glass vial (5 mL) with a bromobutyl rubber stopper and an aluminium seal/white plastic flip-off cap.
Pack sizes of 1 or 30 vials.
Not all pack sizes may be marketed.
The patient will receive a carton containing 1 or 30 vials of Myalepta, depending on the pack size, which should be stored in a refrigerator until the day of use.
The patient will also receive separately the solvent for reconstitution (i.e. water for injection), the syringes/needles for reconstitution, the syringes/needles for administration, the cleansing alcohol swabs, and a sharps disposal container.
Myalepta reconstituted with water for injection is for single use only and should be administered immediately. Unused reconstituted solution cannot be stored for later use. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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