Adult growth hormone deficiency (AGHD)

Active Ingredient: Somapacitan

Indication for Somapacitan

Population group: only children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Curative procedure

Somapacitan is indicated for the replacement of endogenous growth hormone (GH) in children aged 3 years and above, and adolescents with growth failure due to growth hormone deficiency (paediatric GHD), and in adults with growth hormone deficiency (adult GHD).

For this indication, competent medicine agencies globally authorize below treatments:

1-4 mg once weekly

For:

Dosage regimens

Regimen A, in the case that patient age in years is < 60 :

Subcutaneous, 1.5 milligrams somapacitan, once weekly.

Regimen B, in the case that patient age in years is ≥ 60 :

Subcutaneous, 1 milligrams somapacitan, once weekly.

Regimen C, in the case that patient is female and there is estrogen receptor agonist :

Subcutaneous, 2 milligrams somapacitan, once weekly.

Detailed description

Table 1. Dose recommendation:

Adult GHDRecommended starting dose
Naïve patients
Adults (≥18 to <60 years)
Women on oral oestrogen therapy (irrespective of
age)
Elderly (60 years or older)

1.5 mg/week
2 mg/week

1 mg/week
Patients switching from daily GH medicinal
products

Adults (≥18 to <60 years)
Women on oral oestrogen therapy (irrespective of
age)
Elderly (60 years or older)


2 mg/week
4 mg/week

1.5 mg/week

Dose titration

The somapacitan dose must be individually adjusted for each patient. It is recommended to increase the dose gradually with 2-4 weeks intervals in steps from 0.5 mg to 1.5 mg based on the patients' clinical response and experience of adverse reactions up to a dose of 8 mg somapacitan per week. Serum insulin like growth factor-I (IGF-I) levels (drawn 3-4 days after dosing) can be used as guidance for the dose titration. The IGF-I standard deviation score (SDS) target should aim for the upper normal range not exceeding 2 SDS. IGF-I SDS levels in the target range are usually achieved within 8 weeks of dose titration. Longer dose titration may be necessary in some AGHD patients.

Elderly (60 years or older)

Generally, lower doses of somapacitan may be necessary in older patients.

Treatment evaluation

Using IGF-I SDS as a biomarker for dose titration, the aim is to reach IGF-I SDS levels within the age-adjusted upper reference range (IGF-I SDS upper reference range: 0 and +2) within 12 months of titration. If this target range cannot be achieved within this period, or the patient does not obtain the desired clinical response, other treatment options should be considered.

During somapacitan maintenance treatment, evaluation of efficacy and safety should be considered at approximately 6- to 12-month intervals and may be assessed by evaluating biochemistry (IGF-I-, glucose-, and lipid levels), body composition, and body mass index.

Switching from other growth hormone products

Patients switching from a weekly growth hormone to somapacitan are recommended to continue administration at their once weekly dosing day.

Patients switching from daily human growth hormone to once-weekly somapacitan should choose the preferred day for the weekly dose and inject the final dose of daily treatment the day before (or at least 8 hours before) injecting the first dose of once-weekly somapacitan. Patients should follow the instructions for the dose presented in Table 1.

Oral oestrogen therapy

Females on oral oestrogen-containing therapy may have reduced IGF-I levels and may require dose adjustment of growth hormone to achieve the treatment goal. In paediatric GHD doses above 0.16 mg/kg/week have not been studied and are not recommended.

Missed dose

Patients who miss a dose are advised to inject once-weekly somapacitan upon discovery as soon as possible, within 3 days after the missed dose, and then resume their usual once-weekly dosing schedule. If more than 3 days have passed, the dose should be skipped and the next dose should be administered on the regularly scheduled day. If two or more doses have been missed, the dose should be resumed on the regularly scheduled day.

Changing the dosing day

The day of weekly injection can be changed as long as the time between two doses is at least 4 days. After selecting a new dosing day, the once weekly dosing should be continued.

Flexibility in dosing time

On occasions when injection at the scheduled dosing day is not possible, once-weekly somapacitan can be administered up to 2 days before or 3 days after the scheduled weekly dosing day as long as the time between two doses is at least 4 days (96 hours). Once-weekly dosing for the next dose could be resumed at the regularly scheduled dosing day.

Dosage considerations

Somapacitan is to be administered once-weekly at any time of the day.

Somapacitan is to be injected subcutaneously in the abdomen, thighs, buttocks or upper arms without dose adjustment.

The injection site should be rotated every week to prevent local lipoatrophy.

0.16 mg/kg/week

For:

Dosage regimens

In the case that patient age in years is ≥ 3 :

Subcutaneous, 0.16 milligrams somapacitan per kilogram of body weight, once weekly.

Detailed description

Table 1. Dose recommendation:

Paediatric GHDRecommended starting dose
Treatment-naïve paediatric patients and paediatric
patients switching from other GH medicinal
products
0.16 mg/kg/week

Dose titration

Somapacitan dose may be individualised and adjusted based on growth velocity, adverse reactions, body weight and serum insulin-like growth factor I (IGF-I) concentrations.

Average IGF-I standard deviation score (SDS) levels (drawn 4 days after dosing) can guide dose titration. Dose adjustments should be targeted to achieve average IGF-I SDS levels in the normal range, i.e. between -2 and +2 (preferably close to 0 SDS).

If the IGF-I (SDS) is >2, it should be reassessed after a subsequent somapacitan administration. If the value remains >2, reducing the dose by 0.04 mg/kg/week is recommended. More than one dose reduction may be required in some patients.

In patients who have had the dose reduced but are not growing well, the dose may be gradually increased as tolerated up to a maximum dose of 0.16 mg/kg/week. Dose increments should not exceed 0.02 mg/kg per week.

Treatment evaluation

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-I, hormones, glucose, and lipid levels) and pubertal status. More frequent evaluations should be considered during puberty.

Treatment should be discontinued in patients having achieved final height or near final height, i.e. an annualised height velocity <2 cm/year and a bone age >14 years in girls or >16 years in 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.

When GHD persists after growth completion, growth hormone treatment should be continued to achieve full somatic adult development including lean body mass and bone mineral accrual (for guidance on dosing see recommended dose for adults (Table 1)).

Switching from other growth hormone products

Patients switching from a weekly growth hormone to somapacitan are recommended to continue administration at their once weekly dosing day.

Patients switching from daily human growth hormone to once-weekly somapacitan should choose the preferred day for the weekly dose and inject the final dose of daily treatment the day before (or at least 8 hours before) injecting the first dose of once-weekly somapacitan. Patients should follow the instructions for the dose presented in Table 1.

Oral oestrogen therapy

Females on oral oestrogen-containing therapy may have reduced IGF-I levels and may require dose adjustment of growth hormone to achieve the treatment goal. In paediatric GHD doses above 0.16 mg/kg/week have not been studied and are not recommended.

Missed dose

Patients who miss a dose are advised to inject once-weekly somapacitan upon discovery as soon as possible, within 3 days after the missed dose, and then resume their usual once-weekly dosing schedule. If more than 3 days have passed, the dose should be skipped and the next dose should be administered on the regularly scheduled day. If two or more doses have been missed, the dose should be resumed on the regularly scheduled day.

Changing the dosing day

The day of weekly injection can be changed as long as the time between two doses is at least 4 days. After selecting a new dosing day, the once weekly dosing should be continued.

Flexibility in dosing time

On occasions when injection at the scheduled dosing day is not possible, once-weekly somapacitan can be administered up to 2 days before or 3 days after the scheduled weekly dosing day as long as the time between two doses is at least 4 days (96 hours). Once-weekly dosing for the next dose could be resumed at the regularly scheduled dosing day.

Dosage considerations

Somapacitan is to be administered once-weekly at any time of the day.

Somapacitan is to be injected subcutaneously in the abdomen, thighs, buttocks or upper arms without dose adjustment.

The injection site should be rotated every week to prevent local lipoatrophy.

Active ingredient

Somapacitan

Somapacitan is a long-acting recombinant human growth hormone derivative. The mechanism of action of somapacitan is either directly via the GH-receptor and/or indirectly via IGF-I produced in tissues throughout the body, but predominantly by the liver. When growth hormone deficiency is treated with somapacitan a normalisation of body composition (i.e., decreased body fat mass, increased lean body mass) and of metabolic action is achieved.

Read more about Somapacitan

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