Genotropin is contraindicated 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
• Prader-Willi syndrome in children who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment
• Active malignancy
• Hypersensitivity to somatropin or any of its excipients
• Active proliferative or severe non-proliferative diabetic retinopathy
• Pediatric patients with closed epiphyses

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 amounts 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. The potential benefit of treatment continuation with somatropin in patients having acute critical illnesses should be weighed against the potential risk.

Prader-Willi Syndrome in Children: Fatalities have been reported after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome 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 Prader-Willi syndrome 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 Prader-Willi syndrome 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 therapy. Children with certain rare genetic causes of short stature have an increased risk of developing malignancies. Monitor for development of neoplasms. Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi.

Impaired Glucose Tolerance and Diabetes Mellitus: Treatment may decrease insulin sensitivity, particularly at higher doses. New-onset Type 2 diabetes mellitus has been reported. Monitor glucose levels periodically, especially in those with risk factors for diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs may require adjustment when somatropin therapy is instituted.

Intracranial Hypertension (IH): has been reported in patients treated with somatropin, usually within the first 8 weeks of treatment initiation. Perform fundoscopic examination before initiating treatment and periodically thereafter. If papilledema is identified, evaluate the etiology, and treat the underlying cause before initiating somatropin. Temporarily discontinue Genotropin in patients with evidence of IH. If IH is confirmed, restart Genotropin at a lower dose after IH signs and symptoms have resolved. Patients with Turner syndrome and Prader-Willi syndrome may be at increased risk.

Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported. Inform patients and caregivers of the risk and that prompt medical attention should be sought if an allergic reaction occurs.

Fluid Retention: may occur in adults. Clinical manifestations are usually transient and dose dependent.

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 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: Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, particularly in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. Central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Monitor thyroid function periodically and appropriately initiate or adjust thyroid hormone replacement therapy.

Slipped Capital Femoral Epiphyses in Pediatric Patients: May occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth and lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Evaluate pediatric patients with the onset of a limp or complaints of hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly.

Progression of Preexisting Scoliosis in Pediatric Patients: can occur in patients who experience rapid growth. Monitor patients with a history of scoliosis for progression of scoliosis.

Otitis Media and Cardiovascular Disorders in Turner Syndrome: Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders and cardiovascular disorders. Somatropin treatment may increase the occurrence of otitis media in these patients.

Lipoatrophy: Tissue atrophy may result when somatropin is administered at the same site over a long period of time. Rotate injection sites to reduce this risk.

Laboratory Tests: Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and IGF-1 may increase during therapy.

Pancreatitis: Cases have been reported in children and adults receiving treatment. The risk may be greater in children compared with adults and girls who have Turner syndrome than other somatropin-treated children. Consider pancreatitis in patients who develop persistent severe abdominal pain.

ADVERSE REACTIONS

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

DRUG INTERACTIONS

11 β-Hydroxysteroid Dehydrogenase Type 1: Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations.

Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid replacement dosing in children receiving glucocorticoid treatment to avoid both hypoadrenalism and an inhibitory effect on growth.

Cytochrome P450-Metabolized Drugs: Genotropin may alter the clearance. Monitor carefully if used with Genotropin.

Oral Estrogen: Larger doses of Genotropin may be required.

Insulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required.

• growth failure due to an inadequate secretion of endogenous growth hormone.
• growth failure due to Prader-Willi syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing.
• growth failure in children born small for gestational age who fail to manifest catch-up growth by age 2 years.
• growth failure associated with Turner syndrome.
• idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) ≤ -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.

Genotropin is indicated for replacement of endogenous growth hormone in adults with either adult or childhood onset growth hormone deficiency.
GHD should be confirmed as appropriate.