Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The commonly reported adverse reactions after treatment with somatrogon are injection site reactions (ISRs) (25.1%), headache (10.7% ) and pyrexia (10.2%).

Tabulated list of adverse reactions

Safety data are derived from the phase 2, multi-centre safety and dose-finding study, and the pivotal phase 3, multi-centre non-inferiority study in paediatric patients with GHD (see section 5.1). The data reflect exposure of 265 patients to somatrogon administered once weekly (0.66 mg/kg/week).

Table 1 presents the adverse reactions for somatrogon within the system organ class (SOC). The adverse reactions listed in the table below are presented by SOC and frequency categories, 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) or frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 1. Adverse reactions
System organ class               Very            Common           Uncommon        Rare       Very    Frequency common                                                        rare    not known Blood and lymphatic                              Anaemia system disorders                               Eosinophilia
Endocrine disorders                           Hypothyroidism         Adrenal insufficiency
Nervous system                Headache disorders
Eye disorders                                  Conjunctivitis allergic
Skin and subcutaneous                                                Rash tissue disorders                                                  generalised Musculoskeletal and                              Arthralgia connective tissue                             Pain in extremity disorders
General disorders and        Injection site administration site            reactionsa conditions                      Pyrexia

System organ class                    Very                 Common               Uncommon             Rare         Very      Frequency common                                                                        rare      not known a Injection site reactions include the following: injection site pain, erythema, pruritus, swelling, induration, bruising, haemorrhage, warmth, hypertrophy, inflammation, deformation, urticaria.

Description of selected adverse reactions

Injection site reaction
In the phase 3 clinical study, reporting of ISRs was actively solicited during the course of the study. In the majority of cases, local ISRs tended to be transient, occurred mainly in the first 6 months of treatment and were mild in severity; ISRs had a mean onset on the day of the injection and a mean duration of < 1 day. Among them, injection site pain, erythema, pruritus, swelling, induration, bruising, hypertrophy, inflammation and warmth were reported in 43.1% of patients treated with somatrogon compared to 25.2% of patients administered daily injections of somatropin.

In the long-term OLE of the clinical phase 3 study, local ISRs were similar in nature and severity, and reported early in subjects switching from somatropin to somatrogon treatment. ISRs were reported in 18.3% of patients originally treated with somatrogon in the main study and continuing treatment in the OLE portion of the study, and likewise, 37% were reported among patients originally treated with somatropin that were switched in the OLE portion of the study to treatment with somatrogon.

Immunogenicity
In the pivotal safety and efficacy study, among 109 subjects treated with somatrogon, 84 (77.1%) tested positive for anti-drug antibodies (ADAs). There were no clinical or safety effects observed with the formation of antibodies.

Other adverse drug reactions for somatropin may be considered class effects, such as:
•     Neoplasms benign and malignant: (see section 4.4).
•     Metabolism and nutrition disorders: diabetes mellitus type 2 (see section 4.4).
•     Nervous system disorders: benign intracranial hypertension (see section 4.4), paraesthesia.
•     Musculoskeletal, connective tissue, and bone disorders: myalgia.
•     Reproductive system and breast disorders: gynaecomastia.
•     Skin and subcutaneous tissue disorders: skin rash, urticaria and pruritus.
•     General disorders and administration site conditions: peripheral oedema, facial oedema.
•     Gastrointestinal disorders: pancreatitis (see section 4.4).

Metacresol
This medicinal product contains metacresol which may contribute to painful injections (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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/