Nutropin AQ^®

(somatropin) injection for subcutaneous use

Indications & Important Safety Information

INDICATIONS

Nutropin therapy is indicated for the treatment of pediatric patients who have short stature or growth failure as a result of:

• Growth hormone deficiency (GHD)
• Idiopathic short stature (ISS), defined by height standard deviation score ≤ -2.25, associated with growth rates unlikely to result in normal adult height, in whom other causes of short stature have been excluded
• Turner syndrome (TS)
• Chronic kidney disease (CKD) up to the time of renal transplantation

Nutropin therapy is indicated for the replacement of endogenous GH in adults with GH deficiency, either:

• Adult-onset, as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
• Childhood-onset. Patients treated for GH deficiency in childhood who have closed epiphyses should be reevaluated

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• Acute Critical Illness: Somatropin should not be used to treat patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure.
• Prader-Willi Syndrome (PWS) in Children: Somatropin is contraindicated in patients with PWS who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death after initiation of somatropin treatment in such patients. Nutropin AQ is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS.
• Active Malignancy: Somatropin is contraindicated in patients with any evidence of active malignancy. Growth hormone deficiency may be an early sign of a pituitary tumor or other intracranial tumor; the presence of such a tumor should be excluded before initiation of somatropin treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor.
• Hypersensitivity: Nutropin AQ is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products.
• Diabetic Retinopathy: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed Epiphysis: Somatropin should not be used for growth promotion in pediatric patients with closed epiphysis.

WARNINGS AND PRECAUTIONS

• Acute Critical Illness: Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic doses of somatropin. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established.
• Prader-Willi Syndrome (PWS) in Children: There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with PWS who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with PWS should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with PWS treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively.
• Neoplasms: 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 has been reported. Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor. Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi. Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, these patients should be carefully monitored for development of neoplasms, if treatment with somatropin is initiated.
• Glucose Intolerance and Diabetes Mellitus: Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New-onset type 2 diabetes mellitus has been reported. As a result, blood glucose concentrations should be monitored periodically in all patients taking somatropin, especially in those with risk factors for diabetes mellitus. Patients with pre-existing type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin treatment. The doses of antihyperglycemic drugs (i.e. insulin or oral/injectable agents) may require adjustment when somatropin therapy is instituted in these patients.
• Intracranial Hypertension (IH): Funduscopic examination is recommended at the initiation of and periodically during therapy as intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting have been reported in a small number of patients treated with somatropin. If papilledema is observed by funduscopy during treatment with somatropin, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with TS, CKD, and PWS may be at increased risk for the development of IH.
• Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reaction and angioedema have been reported with postmarketing use of somatropin products. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs.
• Fluid Retention: Transient and dose-dependent fluid retention during somatropin replacement in adults may occur.
• Hypoadrenalism: Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment.
• Hypothyroidism: Patients treated with somatropin should have periodic thyroid function tests, and thyroid hormone replacement therapy should be initiated or appropriately adjusted in cases of unmasked or worsening hypothyroidism.
• Slipped Capital Femoral Epiphysis in Pediatric Patients (SCFE): SCFE may occur more frequently in patients with endocrine disorders and in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.
• Progression of Preexisting Scoliosis in Pediatric Patients:Progression of scoliosis can occur in patients who experience rapid growth. Somatropin has not been shown to increase the occurrence of scoliosis. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy.
• Otitis Media and Cardiovascular Disorders in Patients with Turner Syndrome: Patients with TS should be evaluated carefully for otitis media and other ear disorders as somatropin treatment may increase the occurrence of otitis media in these susceptible patients. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (eg, hypertension, aortic aneurysm or dissection, stroke) as they are at increased risk for these conditions.
• Osteodystrophy in Pediatric Patients with Chronic Kidney Disease: Children with growth failure secondary to CKD should be examined periodically for evidence of progression of renal osteodystrophy. SCFE or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy. X-rays of the hip should be obtained prior to initiating somatropin therapy in CKD patients and physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in these patients.
• Lipoatrophy: When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site.
• Laboratory Tests: Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone and IGF-I may increase during somatropin therapy.
• Pancreatitis: Cases of pancreatitis have been reported rarely in children and adults receiving somatropin. Pancreatitis should be considered in any somatropin-treated patient, especially a child, who develops persistent, severe abdominal pain. Girls who have TS may be at greater risk than other somatropin-treated children.

DRUG INTERACTIONS

• Somatropin inhibits 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD-1) in adipose/hepatic tissue and may significantly impact the metabolism of cortisol and cortisone. As a consequence, in patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked, requiring glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment.
• Glucocorticoid replacement therapy should be carefully adjusted in children with concomitant GH and glucocorticoid deficiency to avoid both hypoadrenalism and an inhibitory effect on growth. Concomitant glucocorticoid therapy may inhibit the growth promoting effect of Nutropin AQ.
• Careful monitoring is advisable when somatropin is administered in combination with other drugs metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine), hormone replacement therapy, insulin and/or other hypoglycemic agents.

USE IN SPECIFIC POPULATIONS

• Pregnancy/Nursing Mothers: Somatropin should be used during pregnancy only if clearly needed and with caution in nursing mothers because it is not known whether somatropin is excreted in human milk.
• Geriatric Use: Clinical studies of somatropin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger patients. Elderly patients may be more sensitive to the action of somatropin and may be more prone to adverse reactions.

ADVERSE REACTIONS

• Common adverse reactions reported in adult and pediatric patients taking somatropin include injection site reactions. Additional common adverse reactions in adults include edema, arthralgia, and carpal tunnel syndrome

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see accompanying Nutropin full Prescribing Information for additional Important Safety Information.