Lonapegsomatropin

Concomitant treatment with glucocorticoids inhibits the growth-promoting effects of lonapegsomatropin. Patients with adrenocorticotropic hormone (ACTH) deficiency should have their glucocorticoid replacement therapy carefully adjusted to avoid any inhibitory effect on growth, and patients treated with glucocorticoids should have their growth monitored carefully to assess the potential impact of glucocorticoid treatment on growth.

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

Drug-drug interaction studies have not been performed with lonapegsomatropin. Data from interaction studies with somatropin performed in growth hormone deficient children and adults, and healthy elderly men, suggest that somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes, especially CYP3A and CYP1A2. The clearance of compounds metabolised by CYP 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) and CYP1A2 (e.g. theophylline) may be increased and could result in lower exposure of these compounds. The clinical significance of this is unknown.

In patients with diabetes mellitus requiring therapy with a medicinal product (e.g, anti-hyperglycaemic medicinal products), the dose of insulin and/or oral hypoglycaemic medicinal product may require adjustment when lonapegsomatropin therapy is initiated.

Because growth hormone increases the extrathyroidal conversion of T4 to T3, adjustment of thyroid hormone replacement therapy may be necessary.

Oral oestrogen influences the IGF-1 response to growth hormone. If a female patient taking lonapegsomatropin begins oral oestrogen containing therapy, the dose of lonapegsomatropin may need to be increased to maintain the serum IGF-1 levels within the normal age appropriate range. Conversely, if a female patient on lonapegsomatropin discontinues oral oestrogen containing therapy, the dose of lonapegsomatropin may need to be reduced to avoid excess of growth hormone and/or adverse reactions.

In patients with endocrine disorders, including GHD, slipped epiphyses of the hip may occur more frequently than in the general population. Children with persistent hip/knee pain and/or limping during treatment with lonapegsomatropin should be examined clinically.

Lonapegsomatropin has not been studied in patients with Prader-Willi syndrome. Lonapegsomatropin is not indicated for the long-term treatment of paediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome unless they also have a diagnosis of GHD. There have been reports of sudden death after initiating therapy with growth hormone in patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnoea, or unidentified respiratory infection.

There are no or limited amount of data from the use of lonapegsomatropin in pregnant women; published studies with short-acting somatropin use in pregnant women over several decades have not identified any drug-associated risk of major birth defects, miscarriages, or adverse maternal or foetal outcomes.

Animal studies are insufficient with respect to reproductive toxicity. Lonapegsomatropin is not recommended during pregnancy and in women of childbearing potential not using contraception.

There are no data on the presence of lonapegsomatropin in human milk or effect on the breastfed newborns/infants. As lonapegsomatropin is not orally absorbed, it is unlikely to adversely affect the breastfed newborns/infants.

Lonapegsomatropin can be used during breastfeeding on strict indication.

Fertility

There are no clinical data on the effect of lonapegsomatropin on fertility. Animal studies are insufficient with respect to fertility.

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

Summary of safety profile

The most frequently reported adverse reactions in clinical trials with lonapegsomatropin were headache (11.1%), arthralgia (4.6%), secondary hypothyroidism (2.6%), and injection site reactions (1.6%). In general, these reactions tended to be transient and severity was mild to moderate.

Tabulated list of adverse reactions

The table below shows adverse reactions which occurred during lonapegsomatropin treatment. The adverse reactions are ranked under headings of MedDRA system organ class and frequency using the following terminology: 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), and frequency not known (cannot be estimated from the available data).

Frequency of adverse reactions in clinical trials:

^a Injection site reactions include hyperaemia, injection site atrophy, injection site pain, injection site urticaria, and localised oedema. The injection site reactions observed with lonapegsomatropin were generally mild and transient.

Description of selected adverse reactions

Immunogenicity

Patients may develop antibodies to lonapegsomatropin. The proportion of patients testing positive for detectable binding antibodies at any time during treatment was low (6.3%) and no patients had neutralising antibodies. No apparent correlation of anti-lonapegsomatropin binding antibodies to adverse events or loss of efficacy was observed. In case of an otherwise unexplained lack of response to lonapegsomatropin treatment, testing for antibodies to lonapegsomatropin should be considered.

Adverse reactions related to growth hormone pharmacological class

In addition to the above-mentioned adverse drug reactions, those presented below have been reported with other growth hormone-containing products. Frequencies of these adverse events cannot be estimated from the available data (unless otherwise indicated).

Neoplasms benign, malignant and unspecified (including cysts and polyps): leukaemia.

Metabolism and nutrition disorders: diabetes mellitus type 2.

Nervous system disorders: benign intracranial hypertension, paraesthesia.

Musculoskeletal and connective tissue disorders: myalgia.

Reproductive system and breast disorders: gynaecomastia (frequency: uncommon).

Skin and subcutaneous tissue disorders: skin rash, urticaria and pruritus.

General disorders and administration site conditions: peripheral oedema, facial oedema.