Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Growth hormone deficient patients are characterised by extracellular volume deficit. When treatment with somatropin is initiated, this deficit is corrected. Fluid retention with peripheral oedema may occur especially in adults. Carpal tunnel syndrome is uncommon, but may be seen in adults. The symptoms are usually transient, dose dependent and may require transient dose reduction.
Mild arthralgia, muscle pain and paresthesia may also occur but are usually self-limiting.

Adverse reactions in children are uncommon or rare.


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Clinical trial experience:

System organ             Very common   Common              Uncommon            Rare classes                  (≥ 1/10)      (≥ 1/100 to         (≥ 1/1,000 to       (≥ 1/10,000 to < 1/10)             < 1/100)            < 1/1,000)

Metabolism and                                             In adults nutrition disorders                                        Diabetes mellitus type 2
Nervous system                         In adults           In adults carpal disorders                              headache and        tunnel paraesthesia        syndrome. In children headache
Skin and                                                    In adults          In children rash subcutaneous                                               pruritus tissue disorders
Musculoskeletal,                       In adults           In adults muscle    In children connective tissue                      arthralgia, joint   stiffness           arthralgia and disorders                              stiffness and                           myalgia myalgia
Reproductive                                               In adults and system and breast                                          children disorders                                                  Gynecomastia 
General disorders        In adults                         In adults and       In children and administration       peripheral                        children            peripheral site conditions          oedema (see                       injection site      oedema text above)                       pain. In children injection site reaction

In children with Turner syndrome increased growth of hands and feet has been reported during somatropin therapy.

A tendency for increased incidence of otitis media in Turner syndrome patients treated with high doses of Norditropin has been observed in one open-label randomised clinical trial.
However, the increase in ear infections did not result in more ear operations/tube insertions compared to the lower dose group in the trial.

Clinical Trials in Children with Noonan Syndrome

Norditropin was studied in 21 pediatric patients, 3 years to 14 years of age at doses of 0.033 mg/kg/day and 0.066 mg/kg/day. After the two-year study, patients continued Norditropin treatment until final height was achieved; randomized dose groups were not maintained.
Adverse reactions were later collected retrospectively from 18 pediatric patients; total follow- up was 11 years. An additional 6 pediatric patients were not randomized, but followed the protocol and are included in this assessment of adverse reactions.
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The most frequent adverse reactions were upper respiratory infection, gastroenteritis, ear infection, and influenza. Cardiac disorders was the system organ class with the second most adverse reactions reported. Scoliosis was reported in 1 and 4 pediatric patients receiving doses of 0.033 mg/kg/day and 0.066 mg/kg/day respectively. The following additional adverse reactions also occurred once: insulin resistance and panic reaction for the 0.033 mg/kg/day dose group; injection site pruritus, bone development abnormal, depression, and self-injurious ideation in the 0.066 mg/kg/day dose group. Headache occurred in 2 cases in the 0.066 mg/kg/day dose group.

Post-marketing experience:

In addition to the above mentioned adverse drug reactions, those presented below have been spontaneously reported and are by an overall judgement considered possibly related to Norditropin treatment. Frequencies of these adverse events cannot be estimated from the available data:

- Neoplasms benign and malignant (including cysts and polyps): Leukaemia has been reported in a small number of growth hormone deficiency patients (see section 4.4) - Immune system disorders: Hypersensitivity (see section 4.3). Formation of antibodies directed against somatropin. The titres and binding capacities of these antibodies have been very low and have not interfered with the growth response to Norditropin administration
- Endocrine disorders: Hypothyroidism. Decrease in serum thyroxin levels (see section 4.4)
- Metabolism and nutrition disorders: Hyperglycaemia (see section 4.4) - Nervous system disorders: Benign intracranial hypertension (see section 4.4) - Musculoskeletal and connective tissue disorders: Legg-Calvé-Perthes disease. Legg- Calvé-Perthes disease may occur more frequently in patients with short stature - Investigations: Increase in blood alkaline phosphatase level.

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