ADVERSE REACTIONS SECTION
Growth Hormone Deficient Pediatric Patients
As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. Anti-growth hormone (GH) antibody capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been described. In clinical studies with Saizen® involving 280 patients (204 naive and 76 transfer patients), one patient at 6 months of therapy developed anti-GH antibodies with binding capacities exceeding 2 mg/L. Despite the high binding capacity, these antibodies were not growth attenuating. The patient was subsequently shown to have a hGH-N gene defect. Thus, genetic analysis should be undertaken in any patient in whom anti-GH antibodies with high binding capacities occur. No antibodies against proteins of the host cells were detected in the sera of patients treated up to five years.
Any patient with well-documented growth hormone deficiency who fails to respond to therapy should be tested for antibodies to human growth hormone and for thyroid status.
In clinical studies in which Saizen® was administered to growth hormone deficient children, the following events were infrequently seen: local reactions at the injection site (such as pain, numbness, redness and swelling), hypothyroidism, hypoglycemia, seizures, exacerbation of preexisting psoriasis and disturbances in fluid balance.
Leukemia has been reported in a small number of growth hormone deficient patients treated with growth hormone. It is uncertain whether this increased risk is related to the pathology of growth hormone deficiency itself, growth hormone therapy, or other associated treatments such as radiation therapy for intracranial tumors. So far, epidemiological data fail to confirm the hypothesis of a relationship between growth hormone therapy and leukemia.
Growth Hormone Deficient Adult Patients
During the 6 month placebo-controlled study, adverse events were reported in 56 patients (93.3%) in the somatropin-treated group and 42 patients (76.4%) in the placebo-treated group. Adverse events with an incidence of ≥5% in Saizen®-treated patients which were more frequent in Saizen®-treated patients compared with placebo-treated patients are listed in Table 2. Arthralgia, myalgia, peripheral edema, other types of edema, carpal tunnel syndrome, paraesthesia and hypoaesthesia were common in the somatropin-treated patients and reported more frequently than in the placebo group. These types of adverse events are thought to be related to the fluid accumulating effects of somatropin. During the placebo-controlled portion of the study, approximately 10% of patients without preexisting diabetes mellitus or impaired glucose tolerance treated with somatropin manifested mild, but persistent, abnormalities of glucose tolerance, compared with none in the placebo group. During the open label phase of the study, approximately 10% of patients treated with somatropin required a small upward adjustment of thyroid hormone replacement therapy for preexisting central hypothyroidism and 1 patient was newly diagnosed with central hypothyroidism. In addition, during the open label phase of the study, when all patients were being treated with somatropin, two patients with preexisting central hypoadrenalism required upward titration of hydrocortisone maintenance therapy which was considered to be suboptimal (unrelated to intercurrent stress, surgery or disease), and 1 patient was diagnosed de novo with central adrenal insufficiency after six months of somatropin treatment. Anti-GH antibodies were not detected.
Table 2 - Adverse Events with ≥5% Overall Incidence in Saizen®-Treated Patients Which Were More Frequent in Saizen®-Treated Patients Compared with Placebo-Treated Patients During a 6 Month Study | Adverse Event | Saizen-Treated | Placebo |
| (N=60) | (N=55) |
| N = number of patients |
| Arthralgia | 14(23.3%) | 7(12.7%) |
| Headache | 11(18.3%) | 8(14.5%) |
| Influenza-like symptoms | 9(15.0%) | 3(5.5%) |
| Edema peripheral | 9(15.0%) | 2(3.7) |
| Back pain | 6(10.0%) | 5(9.1%) |
| Myalgia | 5(8.3%) | 2(3.6%) |
| Rhinitis | 5(8.3%) | 2(3.6%) |
| Dizziness | 4(6.7%) | 3(5.5%) |
| Upper respiratory tract infection | 4(6.7%) | 2(3.6%) |
| Paraesthesia | 4(6.7%) | 1(1.8%) |
| Hypoaesthesia | 4(6.7%) | 0 |
| Edema dependent | 3(5.0%) | 2(3.6%) |
| Nausea | 3(5.0%) | 2(3.6%) |
| Skeletal Pain | 3(5.0%) | 1(1.8%) |
| Carpal tunnel syndrome | 3(5.0%) | 1(1.8%) |
| Edema generalized | 3(5.0%) | 0 |
| Chest pain | 3(5.0%) | 0 |
| Depression | 3(5.0%) | 0 |
| Hypothyroidism | 3(5.0%) | 0 |
| Insomnia | 3(5.0%) | 0 |
The adverse event pattern observed during the open label phase of the study was similar to the one presented above.
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