SOGROYA Solution for injection Ref.[27982] Active ingredients: Somapacitan

Traceability

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

Adrenocortical insufficiency

Introduction of growth hormone treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. In patients treated with growth hormone, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of growth hormone treatment. It is necessary to monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or for the need of increased doses of glucocorticoid, see section 4.5.

Glucose metabolism impairment

Treatment with growth hormone may decrease insulin sensitivity, particularly at higher doses in susceptible patients and consequently hyperglycaemia may occur in subjects with inadequate insulin secretory capacity. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during growth hormone treatment. Therefore, glucose levels should be monitored periodically in all patients treated with growth hormone, especially in those with risk factors for diabetes mellitus, such as obesity, or a family history of diabetes mellitus. Patients with pre-existing type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during growth hormone therapy. The doses of antihyperglycaemic medicinal products may require adjustment when growth hormone therapy is instituted in these patients.

Neoplasms

There is no evidence for increased risk of new primary cancers in adults treated with growth hormone. In patients in complete remission from malignant diseases or who have been treated for benign tumours, growth hormone therapy has not been associated with an increased relapse rate.

Patients who have achieved complete remission of malignant diseases or who have been treated for benign tumours should be followed closely for relapse after commencement of growth hormone therapy. Growth hormone treatment should be interrupted in case of any development or reoccurrence of malignant or benign tumour.

An overall slight increase in second neoplasms has been observed in childhood cancer survivors treated with growth hormone, with the most frequent being intracranial tumours. The dominant risk factor for secondary neoplasms seems to be prior exposure to radiation.

Benign intracranial hypertension

In the event of severe or recurrent headache, visual symptoms, nausea, and/or vomiting, a fundoscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension should be considered and if appropriate the growth hormone treatment should be discontinued. At present there is insufficient evidence to guide clinical decision making in patients with resolved intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.

Thyroid function

Growth hormone increases the extrathyroidal conversion of T4 to T3 and may as such unmask incipient hypothyroidism. As hypothyroidism interferes with the response to growth hormone therapy, patients should have their thyroid function tested regularly and should receive replacement therapy with thyroid hormone when indicated, see sections 4.5 and 4.8.

Use with oral oestrogen

Oral oestrogen influences the IGF-I response to growth hormone including somapacitan. Women taking any form of oral oestrogen (hormone therapy or contraception) should consider changing the route of oestrogen administration (e.g. transdermal-, vaginal hormone products) or use another form of contraception. If a woman on oral oestrogen is starting somapacitan therapy, higher starting doses and a longer titration period may be required (see section 4.2).

If a woman taking somapacitan begins oral oestrogen therapy, the dose of somapacitan may need to be increased to maintain the serum IGF-I levels within the normal age-appropriate range. Conversely, if a woman on somapacitan discontinues oral oestrogen therapy, the dose of somapacitan may need to be reduced to avoid excess of somapacitan and/or undesirable effects, see sections 4.2 and 4.5.

Lipohypertrophy

When somapacitan is administered at the same site over a long period of time, lipohypertrophy may occur. The injection site should be rotated to reduce the risk, see sections 4.2 and 4.8.

Antibodies

Although no antibodies were observed after treatment with somapacitan, antibodies could be expected as observed with other therapeutic proteins. Testing for presence of anti-somapacitan antibodies should be carried out in patients who fail to respond to therapy.

Acute critical illness

The effect of growth hormone on recovery was studied in two placebo controlled trials involving 522 critical ill adult patients suffering from complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. Mortality was higher in patients treated with 5.3 or 8 mg growth hormone daily compared to patients receiving placebo, 42% vs 19%. Based on this information, these types of patients should not be treated with somapacitan. As there is no information available on the safety of growth hormone substitution therapy in acutely critical ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved.

Growth hormone deficiency in adults is a lifelong disease and needs to be treated accordingly, however, experience in patients older than 60 years and in patients with more than five years of treatment in adult growth hormone deficiency is still limited.

Paediatric population

Somapacitan should not be administered to patients below 18 years since safety and efficacy of somapacitan in children and adolescents below 18 years have not yet been established.

Sodium

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

Cytochrome P450 metabolised drugs

Data from an interaction study performed in growth hormone deficient adults suggests that growth hormone administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes. The clearance of compounds metabolised by cytochrome P450 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine) may be especially increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.

Glucocorticoids

Growth hormone decreases the conversion of cortisone to cortisol and may unmask previously undiscovered central hypoadrenalism or render low glucocorticoid replacement doses ineffective, see section 4.4.

Oral oestrogens

In women on oral oestrogen therapy, a higher dose of somapacitan may be required to achieve the treatment goal, see sections 4.2 and 4.4.

Antihyperglycaemic products

Antihyperglycaemic treatment including insulin may require dose adjustment in case of somapacitan co-administration since somapacitan may decrease insulin sensitivity, see sections 4.4 and 4.8.

Other

The metabolic effects of somapacitan can also be influenced by concomitant therapy with other hormones, e.g. testosterone and thyroid hormones, see section 4.4.

Pregnancy

There are no data from the use of somapacitan in pregnant women.

Studies in animal have shown reproductive toxicity, see section 5.3.

Sogroya is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is unknown whether somapacitan/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of somapacitan in milk, see section 5.3.

A risk to the breastfed newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Sogroya therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

There is no clinical experience with somapacitan use and its potential effect on fertility. No adverse effects were observed on male and female fertility in rats, see section 5.3.

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

Summary of safety profile

The commonly reported and serious adverse reactions after treatment with somapacitan are headache (12%), peripheral oedema (4%) and adrenocortical insufficiency (3%).

Tabulated list of adverse reactions

The adverse reactions listed below are based on the compiled safety data from three completed phase 3 trials in patients with AGHD.

The adverse reactions are listed by MedDRA system organ class and frequency category 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).

Table 2. Adverse reactions:

^* In general, these adverse reactions were non-serious, mild or moderate severity and transient.

Description of selected adverse reactions

Peripheral oedema

Peripheral oedema was commonly observed (4%). Growth hormone deficient patients are characterised by extracellular volume deficit. When treatment with growth hormone products is initiated, this deficit is corrected. Fluid retention with peripheral oedema may occur. The symptoms are usually transient, dose dependent and may require transient dose reduction.

Adrenocortical insufficiency

Adrenocortical insufficiency was commonly observed (3%), see section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.