Indications and Usage

Norditropin^® [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients with:

• Growth failure due to inadequate secretion of endogenous growth hormone (GH).
• Short stature associated with Noonan or Turner syndrome.
• Short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years.

Norditropin^® is also indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:

• Adult Onset: Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma.
• Childhood Onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Important Safety Information

Contraindications

Somatropin is contraindicated in:

• Acute critical illness: Patients with acute critical illness due to complications following open heart or abdominal surgery or multiple accidental trauma, or those with acute respiratory failure.
• Prader-Willi Syndrome in children: Patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment.
• Active malignancy: Patients with active malignancy. Discontinue somatropin if there is evidence of recurrent activity.
• Diabetic retinopathy: Patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed epiphysis: Children with closed epiphyses.
• Hypersensitivity: Patients with known hypersensitivity to somatropin or any of its excipients.

Warnings and Precautions

• Acute critical illness: Increased mortality in patients due to complications following open heart or abdominal surgery or multiple accidental trauma, or those with respiratory failure has been reported. The potential benefit should be weighed against the potential risk.
• Prader-Willi Syndrome in children: Fatalities have been reported after initiating treatment with somatropin with one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Evaluate patients for signs of upper airway obstruction and sleep apnea before initiation of treatment.
• Neoplasms: Monitor patients with preexisting tumors for progression or recurrence. In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm, in particular meningiomas, has been reported. Children with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients carefully for increased growth, or potential malignant changes, of preexisting nevi.
• Impaired glucose tolerance and diabetes mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. New-onset type 2 diabetes mellitus has been reported. Monitor glucose levels in all patients, and doses of concurrent antihyperglycemic drugs may require adjustment.
• Intracranial hypertension: Intracranial hypertension has been reported in a small number of patients, usually within the first 8 weeks of somatropin treatment. Funduscopic examination should be performed before initiating treatment and periodically.
• Fluid retention: In adults, fluid retention, usually transient and dose-dependent, may occur frequently.
• Hypothyroidism: Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen. Periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted when indicated.
• Slipped capital femoral epiphysis in pediatric patients: May occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth.
• Progression of preexisting scoliosis in pediatric patients: Progression of scoliosis can occur in patients who experience rapid growth. Patients with a history of scoliosis should be monitored for progression.
• Otitis media and cardiovascular disorders in Turner syndrome: Somatropin therapy may increase the occurrence of otitis media in patients with Turner syndrome. Patients with Turner syndrome should also be monitored for cardiovascular disorders.
• Pancreatitis: Rare cases of pancreatitis have been reported. Pancreatitis should be considered in any patient who develops persistent severe abdominal pain.

Adverse Reactions

• Other common somatropin-related adverse reactions include injection site reactions/rashes, lipoatrophy, and headaches.

Drug Interactions

• Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1: Patients may require initiation of glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance doses.
• Glucocorticoid replacement: Should be carefully adjusted in children to avoid either hypoadrenalism or an inhibitory glucocorticoid effect on growth.
• Cytochrome P450-metabolized drugs: Monitor carefully if used with somatropin. Limited published data suggest somatropin may alter clearance of these compounds.
• Oral estrogen: Larger doses of somatropin may be required.
• Insulin and/or oral/injectable hypoglycemic agents: May require adjustment when somatropin therapy is initiated.

Use in Specific Populations

• Pregnancy and Nursing Mothers: Pregnancy Category C. It is not known whether Norditropin^® can cause fetal harm, can affect reproductive capacity, or whether it is excreted in human milk.
• Geriatric Use: The safety and effectiveness in patients aged 65 and over has not been evaluated in clinical studies.