Somapacitan

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.

No information regarding the use of somapacitan in patients with severe hepatic impairment is available. Caution should be exercised if treating these patients with somapacitan.

Antihyperglycaemic treatment including insulin may require dose adjustment in case of somapacitan co-administration since somapacitan may decrease insulin sensitivity.

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.

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.

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

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

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.

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

Studies in animal have shown reproductive toxicity.

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

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

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 somapacitan 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.

Somapacitan 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).

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%).