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Ngenla 60 mg/1.2 ml. 100 IU

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Ngenla is indicated for the treatment of children and adolescents aged 3 years and older with growth failure due to insufficient secretion of growth hormone.

Quantity

Ngenla is indicated for the treatment of children and adolescents aged 3 years and older with growth failure due to insufficient secretion of growth hormone.

Treatment should be initiated and supervised by physicians qualified and experienced in the diagnosis and treatment of pediatric patients with growth hormone deficiency (GHD).

Posology

The recommended dose is 0.66 mg/kg body weight administered once weekly by subcutaneous injection.

Each pre-filled pen can be used to dial and deliver the dose prescribed by the physician. The dose may be rounded up or down based on the physician’s expertise in the individual patient’s needs.

When a dose greater than 30 mg is required (i.e. in a patient with a body weight > 45 kg), two injections should be administered.

Starting dose for patients switching from once-daily growth hormone medicinal products

For patients switching from once-daily growth hormone medicinal products, once-weekly somatrogon therapy can be initiated at a dose of 0.66 mg/kg/week on the day after the last once-daily injection.

Dose titration

The dose of somatrogon can be adjusted as needed based on growth velocity, adverse reactions, body weight and serum insulin-like growth factor 1 (IGF-1) concentrations.

When monitoring IGF-1 concentrations, samples should always be collected 4 days after the previous dose. Dose adjustments should be made to achieve a mean IGF-1 standard deviation score (SDS) within the normal range, i.e. between -2 and +2 (preferably close to 0 SDS).

In patients whose serum IGF-1 concentrations exceed the mean reference value for their age and sex by more than 2 SDS, the dose of somatrogon should be reduced by 15%. In some patients, more than one dose reduction may be necessary.

Assessment and discontinuation of treatment

Efficacy and safety of treatment should be assessed at approximately 6 to 12 monthly intervals and may include assessment of growth parameters, biochemistry (IGF-1, hormones, blood glucose levels) and pubertal status. Regular monitoring of serum IGF-1 SDS levels is recommended during the course of treatment. More frequent assessments should be made during puberty.

Treatment should be discontinued if there is evidence of epiphyseal closure (see section 4.3). Treatment should also be discontinued in patients who have fully or almost reached their final height, i.e. annual growth velocity < 2 cm/year or bone age

> 14 years in girls or > 16 years in boys.

Missed doses

Patients should adhere to the usual day of administration. If a dose is missed, somatrogon should be administered as soon as possible within 3 days of the missed dose and then the usual once-weekly dosing schedule should be resumed. If more than 3 days have passed, the missed dose should not be administered and the next dose should be administered on the normally scheduled day. In any case, patients may then resume their regular once-weekly dosing schedule.

Change of dosing day

If necessary, the day of weekly administration may be changed, provided that the time between the two doses is at least 3 days. Once a new dosing day has been selected, once-weekly treatment should be continued.

Special populations

Gender

The safety and efficacy of somatrogon in patients over 65 years of age have not been established. Data are not available.

Renal impairment

Somatrogon has not been studied in patients with renal impairment. No dosage recommendations can be made.

Hepatic impairment

Somatrogon has not been studied in patients with hepatic impairment. No dosage recommendations can be made.

Paediatric population

The safety and efficacy of somatrogon in neonates, infants and children under 3 years of age have not yet been established. Data are not available.

Method of administration

Somatrogon is administered by subcutaneous injection.

Somatrogon should be injected into the abdomen, thighs, buttocks or upper arms. The injection site should be rotated with each administration.

Injections into the upper arms and buttocks should be administered by the patient's caregiver.

The patient and caregiver should be trained to ensure that they understand the administration procedure and are able to administer it themselves.

If more than one injection is required to deliver the full dose, each injection should be administered at a different injection site.

Somatrogon should be administered once a week, on the same day of the week, at any time of day.

Ngenla 24 mg solution for injection in pre-filled pen

Prefilled

The pre-filled pen delivers doses from 0.2 mg to 12 mg of somatrogon in steps of 0.2 mg (0.01 ml).

Ngenla 60 mg solution for injection in pre-filled pen

The pre-filled pen delivers doses from 0.5 mg to 30 mg of somatrogon in steps of 0.5 mg (0.01 ml).

For instructions on the medicinal product before administration, see section 6.6 and at the end of the leaflet.

Contraindications

Hypersensitivity to somatrogon (see section 4.4) or to any of the excipients listed in section 6.1.

Somatrogon should not be used when there is evidence of tumour activity based on experience with once-daily growth hormone containing medicinal products. Intracranial tumours must be inactive and anti-tumour treatment must be completed before starting growth hormone (GH) therapy. Treatment should be discontinued if there is evidence of tumour growth (see section 4.4).

Somatrogon should not be used to stimulate growth in children with closed epiphyses.

Patients with acute critical illness, suffering from complications following open heart surgery, abdominal surgery, accidental polytrauma, acute respiratory failure or similar conditions should not be treated with somatrogon (for patients receiving replacement therapy, see section 4.4).

Warnings

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Hypersensitivity

Serious systemic hypersensitivity reactions (e.g. anaphylaxis, angioedema) have been reported with once-daily growth hormone containing medicinal products. If a serious hypersensitivity reaction occurs, somatrogon should be discontinued immediately; patients should be treated promptly according to standard of care and monitored until signs and symptoms resolve (see section 4.3).

Hypoadrenalism

Based on published data, patients receiving once-daily growth hormone therapy who have or are at risk of developing a deficiency of one or more pituitary hormones may be at risk of decreased serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients on glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require increased maintenance or loading doses after initiation of somatrogon therapy (see section 4.5). Patients should be monitored for decreased serum cortisol levels and/or the need for increased glucocorticoid dosage in those with known hypoadrenalism (see section 4.5).

Thyroid dysfunction

Growth hormone increases the extrathyroidal conversion of T4 to T3 and may unmask incipient hypothyroidism. Patients with pre-existing hypothyroidism should be treated as necessary before initiating somatrogon treatment, as indicated by clinical judgment. Since hypothyroidism affects the response to growth hormone therapy, patients should have their thyroid function tested regularly and receive thyroid hormone replacement therapy when indicated (see sections 4.5 and 4.8).

Prader-Willi syndrome

Somatrogon has not been studied in patients with Prader-Willi syndrome. Somatrogon is not indicated for the long-term treatment of paediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome, unless they are also diagnosed with GD. Sudden death has been reported after initiation of growth hormone therapy in paediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction, sleep apnoea or unspecified respiratory infection.

Impaired glucose metabolism

Treatment with growth hormone-containing medicinal products may reduce insulin sensitivity and induce hyperglycaemia. Additional monitoring should be considered in patients treated with somatrogon who have glucose intolerance or additional risk factors for diabetes. In patients treated with somatrogon who have diabetes mellitus, dose adjustment of antihyperglycaemic medicinal products may be necessary (see section 4.5).

Neoplasm

In patients with a previous malignancy, particular attention should be paid to signs and symptoms of relapse. Patients with existing tumors or growth hormone deficiency secondary to an intracranial lesion should be monitored regularly for progression or recurrence of the underlying disease. An increased risk of a second neoplasm has been reported in patients who have survived childhood cancer and who have been treated with somatropin after their first neoplasm. The second neoplasms are most commonly intracranial tumors, particularly meningiomas, in patients treated with somatropin.

with radiotherapy to the head for a first neoplasm.

Benign intracranial hypertension

Intracranial hypertension (IH) with papilloedema, ataxia, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with growth hormone-containing medicinal products. Fundoscopic examination is recommended at the start of treatment and as clinically indicated. Somatrogon should be temporarily discontinued in patients with clinical or fundoscopic evidence of IH. There are currently insufficient data to provide specific advice on the continuation of growth hormone treatment in patients with resolved IH. If somatrogon treatment is restarted, monitoring for signs and symptoms of IH is necessary.

Acute critical illness

In critically ill adult patients suffering from complications following open heart surgery, abdominal surgery, accidental polytrauma or acute respiratory failure, mortality was higher in patients treated with 5.3 mg or 8 mg somatropin daily (i.e. 37.1 - 56 mg/week) compared to patients receiving placebo, 42% versus 19%. Based on these data, such patients should not be treated with somatrogon. As there are no safety data available on the use of growth hormone as replacement therapy in patients with acute critical illness, the benefits of continuing somatrogon treatment in this situation should be carefully weighed against the possible risks. In all patients who develop other or similar acute critical conditions, the benefits of somatrogon treatment should be weighed against the possible risks.

Pancreatitis

Although rare in patients treated with growth hormone-containing medicinal products, pancreatitis should be considered in patients treated with somatrogon who develop severe abdominal pain during treatment.

Scoliosis

Since somatrogon increases growth velocity, signs of development or progression of scoliosis should be monitored during treatment.

Epiphyseal disorders

Epiphyseal disorders, including slipped capital femoral epiphysis, may occur more frequently in patients with endocrine disorders or in patients with rapid growth. All pediatric patients who develop lameness or complain of hip or knee pain during treatment should be carefully evaluated.

Oral estrogen therapy

Oral estrogen affects the response of IGF-1 to growth hormone. If a patient taking somatrogon starts or stops oral estrogen therapy, IGF-1 levels should be monitored to determine whether the dose of growth hormone needs to be adjusted to maintain serum IGF-1 levels within the normal range (see section 4.2). In patients on oral estrogen therapy, a higher dose of somatrogon may be required to achieve the therapeutic goal (see section 4.5).

Excipients

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodium-free.

Metacresol

Myositis is a very rare adverse event that may be related to the preservative metacresol. In case of myalgia or disproportionate pain at the injection site, myositis should be considered and, if confirmed, alternative growth hormone medicinal products that do not contain metacresol should be used.

Thyroid medicinal products

Treatment with growth hormone administered once daily may unmask previously undiagnosed or subclinical central hypothyroidism. Initiation or adjustment of thyroxine replacement therapy may be necessary (see section 4.4).

Oral estrogen therapy

Patients on oral estrogen-containing therapy may require a higher dose of somatrogon to achieve the therapeutic goal (see section 4.4).

Products metabolized by cytochrome P450

Drug-drug interaction studies have not been conducted with somatrogon.

Somatrogon has been shown to induce CYP3A4 mRNA expression in vitro. The clinical significance of this is unknown. Studies with other human growth hormone (hGH) receptor agonists conducted in growth hormone deficient children and adults and healthy elderly men suggest that administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes, particularly CYP3A. The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine) may be increased and may result in lower exposure to these compounds.

Pregnancy

Pregnancy

There are no data from the use of somatrogon in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see

section 5.3). Ngenla is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breastfeeding

It is not known whether somatrogon/metabolites are excreted in human milk. A risk to the newborn/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from somatrogon therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

The risk of infertility in women or men of reproductive potential has not been studied in humans. In a study in rats, male and female fertility was not affected (see section 5.3).

Driving

Ngenla has no or negligible influence on the ability to drive and use machines.

Adverse reactions

Summary of the safety profile

The most commonly reported adverse reactions following treatment with somatrogon were injection site reactions (ISR) (25.1%), headache (10.7%) and pyrexia (10.2%).

Tabulated list of adverse reactions

Safety data were obtained from a multicentre phase 2 safety and dose-finding study and a pivotal multicentre phase 3 efficacy and safety non-inferiority study in paediatric patients with DRD (see section 5.1).

The data reflect exposure to somatrogon in 265 patients treated with somatrogon administered once weekly (0.66 mg/kg/week).

Table 1 presents adverse reactions to somatrogon by system organ class (SOC). The adverse reactions listed in the table below are presented by SOC and frequency category, defined using the following convention: 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 (frequency cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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