Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Patients with growth hormone deficiency are characterized by extracellular volume deficit. When treatment with somatropin is started this deficit is rapidly corrected. In adult patients adverse effects related to fluid retention, such as oedema peripheral, face oedema, musculoskeletal stiffness, arthralgia, myalgia and paraesthesia are common. In general these adverse effects are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose-reduction.

The incidence of these adverse effects is related to the administered dose, the age of patients, and possibly inversely related to the age of patients at the onset of growth hormone deficiency. In children such adverse effects are uncommon.

Genotropin has given rise to the formation of antibodies in approximately 1 % of the patients. The binding capacity of these antibodies has been low and no clinical changes have been associated with their formation, see section 4.4.

Tabulated list of adverse reactions
Table 1 shows the adverse reactions ranked under headings of System Organ Class and frequency for children and adults, 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); not known (cannot be estimated from the available data)

Table 1: Tabulated list of adverse reactions
System organ        Very         Common          Uncommon        Rare        Very rare     Not class               common       (≥1/100 to      (≥1/1,000 to    (≥1/10,00   (<1/10,000)   known (≥1/10)      <1/10)          <1/100)         0 to                      (cannot <1/1000)                  be estimated from available data)
Neoplasms                                        (Children) benign,                                          Leukaemia† malignant, and unspecified
(including cysts and polyps)
Metabolism and                                                                             (Adults nutrition                                                                                  and disorders                                                                                  Children) Type 2 diabetes mellitus




Table 1: Tabulated list of adverse reactions
System organ        Very          Common            Uncommon           Rare          Very rare      Not class               common        (≥1/100 to        (≥1/1,000 to       (≥1/10,00     (<1/10,000)    known (≥1/10)       <1/10)            <1/100)            0 to                         (cannot <1/1000)                     be estimated from available data)
Nervous system                    (Adults)          (Children)                                      (Adults) disorders                         Paraesthesia*     Benign                                          Benign intracranial                                    intracrania
(Adults)          hypertension                                    l
Carpal tunnel                                                     hypertensi syndrome          (Children)                                      on
Paraesthesia*                                   (Adults and
Children)
Headache
Skin and                                            (Children)                                      (Adults) subcutaneous                                        Rash**,                                         Rash**, tissue disorders                                    Pruritus**,                                     Pruritus**, Urticaria**                                     Urticaria*
*
Musculoskeletal     (Adults)      (Adults)          (Children)                                      (Children) and connective      Arthralgia    Myalgia*          Myalgia*                                        Musculosk tissue disorders    *                                                                               eletal (Adults)                                                          stiffness* Musculoskelet al stiffness*

(Children)
Arthralgia*

Reproductive                                        (Adults and system and                                          Children) breast disorders                                    Gynaecomastia
General             (Adults)      (Children)        (Children)                                      (Adults disorders and       Oedema        Injection-site    Oedema                                          and administration      peripheral    reaction$         peripheral*                                     Children) site conditions     *                                                                               Face oedema*

(Adults)
Injection-s ite reaction$

Investigations                                                                                         (Adults and
Children)
Blood cortisol decreased‡
* In general, these adverse effects are mild to moderate, arise within the first months of treatment, and subside spontaneously or with dose-reduction. The incidence of these adverse effects is related to the administered dose, the age of the patients, and possibly inversely related to the age of the patients at the onset of growth hormone deficiency.
** Adverse Drug Reactions (ADR) identified post-marketing.
$ Transient injection site reactions in children have been reported.
‡ Clinical significance is unknown
† Reported in growth hormone deficient children treated with somatropin, but the incidence appears to be similar to that in children without growth hormone deficiency.




Reduced serum cortisol levels
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increased hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of GENOTROPIN therapy.

Prader-Willi syndrome

In the post-marketing experience rare cases of sudden death have been reported in patients affected by Prader-Willi syndrome treated with somatropin, although no causal relationship has been demonstrated.

Leukaemia
Cases of leukaemia have been reported in children with a GH deficiency, some of whom were treated with somatropin and included in the post-marketing experience. However, there is no evidence of an increased risk of leukaemia without predisposition factors, such as radiation to the brain or head.

Slipped capital femoral epiphysis and Legg-Calve-Perthes disease

Slipped capital femoral epiphysis and Legg-Calve-Perthes disease have been reported in children treated with GH. Slipped capital femoral epiphysis occurs more frequently in case of endocrine disorders and Legg-Calve-Perthes is more frequent in case of short stature. But, it is unknown if these 2 pathologies are more frequent or not while treated with somatropin. Their diagnosis should be considered in a child with a discomfort or pain in the hip or knee.


Other adverse drug reactions
Other adverse drug reactions may be considered somatropin class effects, such as possible hyperglycaemia caused by decreased insulin sensitivity, decreased free thyroxin level and benign intra-cranial hypertension.

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/