Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Ascendis Pharma Endocrinology Division A/S, Tuborg Boulevard 12, DK-2900 Hellerup, Denmark
Growth failure in children and adolescents aged from 3 years up to 18 years due to insufficient endogenous growth hormone secretion (growth hormone deficiency [GHD]).
Treatment should be initiated and monitored by physicians who are qualified and experienced in the diagnosis and management of paediatric patients with GHD.
The amount and concentration of lonapegsomatropin is always expressed in terms of mg somatropin referring to the content of the somatropin moiety and not including mPEG-linker in order to prevent medication errors when patients switch from daily somatropin therapy.
The posology and administration should be individualised for each patient.
The recommended starting dose of Skytrofa is 0.24 mg somatropin/kg body weight, given once weekly. The recommended starting dose strengths for such a dose by weight range can be found in Table 1.
Table 1. Recommended dose for patients by weight, when prescribed doses of 0.24 mg somatropin/kg/week:
| Average IGF-1 SDS range (drawn on post-dose day 4-5) | Recommended change in somatropin dose strength |
|---|---|
| > +4 | Reduce by 3 dose strengths |
| +3 to +4 | Reduce by 2 dose strengths |
| +2 to +3 | Reduce by 1 dose strength |
| -2 to +2 | No change |
| < -2 | Increase by 1 dose strength |
If prescribing a dose other than 0.24 mg somatropin/kg/week, calculate the total weekly dose (in mg somatropin) and select the appropriate dose strength as follows:
If changing therapy to once-weekly lonapegsomatropin from daily somatropin, there should be at least 8 hours between the final dose of once-daily somatropin and the first dose of lonapegsomatropin.
In children switching from daily somatropin, physicians may adjust the starting dose taking into consideration the current somatropin dose, individual clinical response, and clinical considerations specific to the patient.
For children switching from daily somatropin medicinal products at a weekly dose equal to or greater than 0.24 mg somatropin/kg body weight, the recommended starting dose of lonapegsomatropin is 0.24 mg somatropin/kg body weight (see Table 1).
For children switching from daily somatropin medicinal products at a weekly dose less than 0.24 mg somatropin/kg body weight, use the previously prescribed weekly dose as the recommended starting dose of lonapegsomatropin (see equation above).
The dose of lonapegsomatropin should be individually adjusted for each patient based on clinical response, adverse reactions, and/or serum insulin-like growth factor-1 (IGF-1) concentrations outside the targeted range. Available somatropin dose strengths can be found in section 1.
Average IGF-1 standard deviation score (SDS) levels (drawn 4-5 days after dosing) can be used as guidance for dose titration (see Table 2). It is necessary to wait a minimum of 2 weeks after initiation of lonapegsomatropin or after any dose change before assessing the resulting IGF-1 SDS levels. Dose adjustments should be targeted to achieve average IGF-1 SDS levels in the normal range, i.e. between -2 and +2 (preferably close to 0 SDS).
IGF-1 SDS levels may vary over time, and therefore routine monitoring of serum IGF-1 SDS levels throughout the course of treatment is recommended, especially during puberty.
Table 2. Recommended change in somatropin dose strength for average IGF-1 SDS categories:
Evaluation of efficacy and safety should be considered at approximately 6- to 12-month intervals and may be assessed by evaluating auxological parameters, biochemistry (IGF-1, hormones, glucose, and lipid levels), and pubertal status. More frequent evaluations should be considered during puberty.
Treatment should be discontinued in patients with annualised height velocity <2 cm/year, final height achievement, height velocity SDS < +1 after the first year of treatment, or in case bone age is >14 years (girls) or >16 years (boys) which corresponds to the closure of the epiphyseal growth plates.
Once the epiphyses are fused, patients should be clinically re-evaluated for the need for growth hormone treatment.
Females on oral oestrogen-containing therapy may require a higher dose of growth hormone to achieve the treatment goal (see section 4.4).
If a dose is missed, it should be administered as soon as possible and no more than 2 days after the missed dose. If more than 2 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
The day of weekly injection can be changed to a different day of the week. Lonapegsomatropin can be administered 2 days before or 2 days after the scheduled dosing day. It should be ensured that at least 5 days will pass between the last dose and the newly-established regular once weekly dosing day.
No information in patients with renal impairment is available and dose recommendations cannot be given.
No information in patients with hepatic impairment is available and dose recommendations cannot be given.
The safety and efficacy of lonapegsomatropin in children under 3 years of age has not been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made.
Each injection should be administered subcutaneously once-weekly in the abdomen, buttock or thigh. The site of administration should be varied to prevent lipoatrophy.
Lonapegsomatropin is intended to be administered after reconstitution of the powder for solution for injection with the enclosed solvent. Lonapegsomatropin should be administered by means of the GH Auto-Injector. The patient and caregiver should receive training to ensure understanding of the administration procedure by means of the device in order to be allowed to (self)-inject lonapegsomatropin.
The reconstituted solution should be colourless and clear to opalescent and free or practically free of visible particles (see section 6.6).
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and the instructions included at the end of the package leaflet.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia. Long-term overdose could result in signs and symptoms of gigantism.
Treatment is symptomatic and supportive. There is no antidote for somatropin overdose. It is recommended to monitor thyroid function following an overdose.
3 years when stored in a refrigerator (2°C-8°C).
Alternatively, Lonapegsomatropin Ascendis Pharma may be stored at temperatures ≤30°C for up to 6 months. Within the 6 months, the medicinal product can be returned to refrigeration (2°C-8°C).
Record the date on the carton when the medicinal product was first removed from the refrigerator. Discard the medicinal product when 6 months have passed.
Chemical and physical in-use stability has been demonstrated for reconstituted product stored for 4 hours at temperatures ≤30°C.
From a microbiological point of view, the product should be used immediately after reconstitution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not exceed 4 hours at temperatures ≤30°C.
Store in refrigerator (2°C-8°C). Do not freeze.
Store in the original package in order to protect from light.
For alternative storage conditions at temperatures ≤30°C, see section 6.3.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Glass cartridge (Type I glass) with two chambers separated by a rubber stopper (bromobutyl). The cartridge is closed by a rubber stopper (bromobutyl) in one end and by a rubber closure disc (bromobutyl) in the other end. The cartridge is mounted in a plastic needle adaptor.
Each pack contains 4 single-use dual-chamber cartridges packed in individual blisters and 6 disposable injection needles 0.25 mm x 4 mm (31G x 5/32"). Each dual-chamber cartridge has a specific label with assigned two-colour coding ribbons that is only used by the Auto-Injector to select the correct reconstitution settings. Strength colours are indicated on the carton and blister foil and should be used to differentiate the individual strengths.
Skytrofa 3 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 3 mg of somatropin as powder in the first chamber and 0.279 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is yellow/green. The strength colour on the carton and blister is light apricot.
Skytrofa 3.6 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 3.6 mg of somatropin as powder in the first chamber and 0.329 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is yellow/cyan. The strength colour on the carton and blister is cyan.
Skytrofa 4.3 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 4.3 mg of somatropin as powder in the first chamber and 0.388 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is yellow/pink. The strength colour on the carton and blister is dark grey.
Skytrofa 5.2 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 5.2 mg of somatropin as powder in the first chamber and 0.464 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is green/pink. The strength colour on the carton and blister is yellow.
Skytrofa 6.3 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 6.3 mg of somatropin as powder in the first chamber and 0.285 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is cyan/yellow. The strength colour on the carton and blister is orange.
Skytrofa 7.6 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 7.6 mg of somatropin as powder in the first chamber and 0.338 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is cyan/pink. The strength colour on the carton and blister is dark purple.
Skytrofa 9.1 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 9.1 mg of somatropin as powder in the first chamber and 0.4 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is pink/yellow. The strength colour on the carton and blister is golden brown.
Skytrofa 11 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 11 mg of somatropin as powder in the first chamber and 0.479 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is pink/green. The strength colour on the carton and blister is dark blue.
Skytrofa 13.3 mg powder and solvent for solution for injection in cartridge:
Each dual-chamber cartridge contains 13.3 mg of somatropin as powder in the first chamber and 0.574 mL of solvent in the second chamber. The cartridge two-colour label (bottom/top) is pink/cyan. The strength colour on the carton and blister is dark red.
If refrigerated, keep at room temperature for 15 minutes before use.
Each Skytrofa dual-chamber cartridge containing the powder and solvent for solution for injection is for single-use only and must only be used with the supplied injection needles and the GH Auto-Injector. The GH Auto-Injector is not included in this pack. The powder for solution for injection must be reconstituted with the enclosed solvent by a GH Auto-Injector after attaching the needle to the dual-chamber cartridge.
The reconstituted solution should be colourless and clear to opalescent and free or practically free of visible particles. The solution may occasionally contain air bubbles. If the solution contains particles, it must not be injected.
Following reconstitution, Skytrofa is administered subcutaneously (automatically dosed) by the GH Auto-Injector.
Skytrofa is dosed as a full single-dose (total use).
Read the instructions for use for preparing Skytrofa provided at the end of the package leaflet and the instructions for use provided with the GH Auto-Injector before use.
The patient should be advised to discard the cartridge and injection needle after each injection. Any unused medicinal product or waste material should be disposed in accordance with local requirements.
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