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 (N=60) Placebo (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.

OVERDOSAGE
Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia.  Moreover, overdose with somatropin is likely to cause fluid retention.

Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess human growth hormone.

DOSAGE AND ADMINISTRATION
Pediatric Growth Hormone Deficiency (GHD)

Saizen® [somatropin (rDNA origin) for injection] dosage and administration schedule should be ind