ADVERSE REACTIONS
As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. GH antibody binding 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 observed. In clinical studies of pediatric patients that were treated with Nutropin® [somatropin (rDNA origin) for injection] for the first time, 0/107 growth hormone–deficient (GHD) patients, 0/125 CRI patients, and 0/112 Turner syndrome, and 0/117 ISS patients screened for antibody production developed antibodies with binding capacities ≥ 2 mg/L at six months. In a clinical study of patients that were treated with Nutropin AQ for the first time, 0/38 GHD patients screened for antibody production for up to 15 months developed antibodies with binding capacities ≥ 2 mg/L.
Additional short‑term immunologic and renal function studies were carried out in a group of patients with CRI after approximately one year of treatment to detect other potential adverse effects of antibodies to GH. Testing included measurements of C1q, C3, C4, rheumatoid factor, creatinine, creatinine clearance, and BUN. No adverse effects of GH antibodies were noted.
In addition to an evaluation of compliance with the prescribed treatment program and thyroid status, testing for antibodies to GH should be carried out in any patient who fails to respond to therapy.
In a post marketing surveillance study, the National Cooperative Growth Study, the pattern of adverse events in over 8000 patients with idiopathic short stature was consistent with the known safety profile of GH, and no new safety signals attributable to GH were identified. The frequency of protocol-defined targeted adverse events is described in the table, below.
Protocol-Defined Targeted Adverse Events in the ISS NCGS Cohort | Reported Events | NCGS
(N=8018) |
|---|
| AVN=avascular necrosis;SCFE=slipped captial femoral epiphysis. |
| Data obtained with several rhGH products (Nutropin, Nutropin AQ, Nutropin Depot and Protropin). |
| Any Adverse event | |
| Overall | 103 (1.3%) |
| Targeted Adverse event | |
| Overall | 103 (1.3%) |
| Injection-site reaction | 28 (0.3%) |
| New onset or progression of scoliosis | 16 (0.2%) |
| Gynecomastia | 12 (0.1%) |
| Any new onset or recurring tumor (benign) | 12 (0.1%) |
| Arthralgia or arthritis | 10 (0.1%) |
| Diabetes mellitus | 5 (0.1%) |
| Edema | 5 (0.1%) |
| Cancer, neoplasm (new onset or recurrence) | 4(0.0%) |
| Fracture | 4(0.0%) |
| Intracranial hypertension | 4(0.0%) |
| Abnormal bone or other growth | 3(0.0%) |
| Central Nervous system tumor | 2(0.0%) |
| New or recurrent SCFE or AVN | 2(0.0%) |
| Carpal tunnel syndrome | 1(0.0%) |
Injection site discomfort has been reported. This is more commonly observed in children switched from another GH product to Nutropin AQ. Experience with Nutropin AQ in adults is limited.
Leukemia has been reported in a small number of GHD patients treated with GH. It is uncertain whether this increased risk is related to the pathology of GH deficiency itself, GH therapy, or other associated treatments such as radiation therapy for intracranial tumors. On the basis of current evidence, experts cannot conclude that GH therapy is responsible for these occurrences. The risk to GHD, CRI, or Turner syndrome patients, if any, remains to be established.
Other adverse drug reactions that have been reported in GH-treated patients include the following:
- 1)Metabolic: mild, transient peripheral edema. In GHD adults, edema or peripheral edema was reported in 41% of GH‑treated patients and 25% of placebo-treated patients;
- 2)Musculoskeletal: arthralgias; carpal tunnel syndrome. In GHD adults, arthralgias and other joint disorders were reported in 27% of GH‑treated patients and 15% of placebo‑treated patients;
- 3)Skin: rare increased growth of pre‑existing nevi; patients should be monitored for malignant transformation; and
- 4)Endocrine: gynecomastia. Rare pancreatitis.
|
