Selected Important Safety Information

Who should not use Norditropin^®?
Do not use Norditropin^® if:

• you have a critical illness caused by certain types of heart or stomach surgery, trauma or breathing (respiratory) problems.
• you are a child with Prader-Willi syndrome who is severely obese or has breathing problems including sleep apnea.
• you have cancer or other tumors.
• your healthcare provider tells you that you have certain types of eye problems caused by diabetes.
• you are a child with closed bone growth plates (epiphyses).
• you are allergic to Norditropin® or any of the ingredients in Norditropin^®.

Indications and Usage

What is Norditropin^® (somatropin [rDNA origin] injection)?

Norditropin^® is a prescription medicine that contains human growth hormone and is used to treat:

• children who are not growing because of low or no growth hormone.
• children who are short (in stature) and who have Noonan syndrome or Turner syndrome.
• children who are short (in stature) because they were born small (small for gestational age-SGA) and have not caught-up in growth by age 2 to 4 years.
• adults who did not make enough growth hormone when they were children or when they became adults.

Important Safety Information

Who should not use Norditropin^®?
Do not use Norditropin^® if:

• you have a critical illness caused by certain types of heart or stomach surgery, trauma or breathing (respiratory) problems.
• you are a child with Prader-Willi syndrome who is severely obese or has breathing problems including sleep apnea.
• you have cancer or other tumors.
• your healthcare provider tells you that you have certain types of eye problems caused by diabetes.
• you are a child with closed bone growth plates (epiphyses).
• you are allergic to Norditropin® or any of the ingredients in Norditropin^®.

What should I tell my health care provider before I start Norditropin^®?
Tell your healthcare provider about all of your medical conditions, including if you:

• have diabetes, had cancer or any tumor, or have any other medical conditions.
• are pregnant or breastfeeding, or plan to become pregnant or breastfeed.
• take any prescription and non-prescription medicines, vitamins or herbal supplements. Norditropin^® may affect how other medicines work, and other medicines may affect how Norditropin^® works.

Tell your healthcare provider about all the medicines you take,

including prescription and over-the-counter medicines, vitamins, and herbal supplements. Norditropin^® may affect how other medicines work, and other medicines may affect how Norditropin^® works.

How should I use Norditropin^®?

• Do not share your Norditropin^® pen and needles with another person. You may give another person an infection or get an infection from them.

What are the possible side effects of Norditropin^®?
Norditropin^® can cause serious side effects, including:

• high risk of death in people who have critical illnesses because of heart or stomach surgery, trauma or serious breathing (respiratory) problems.
• high risk of death in children with Prader-Willi syndrome who are severely obese or have breathing problems including sleep apnea.
• return of tumor or cancerous growths.
• high blood sugar (hyperglycemia).
• increase in pressure in the skull (intracranial hypertension). If you have headaches, eye problems, nausea or vomiting, swollen hands and feet due to fluid retention contact your health care provider right away.
• serious allergic reactions. Get medical help right away if you have the following symptoms: swelling of your face, lips, mouth or tongue, trouble breathing, wheezing, severe itching, skin rashes, redness or swelling, dizziness or fainting, fast heartbeat or pounding in your chest, or sweating
• decrease in a hormone called cortisol
• decrease in thyroid hormone levels.
• hip and knee pain or a limp in children (slipped capital femoral epiphysis).
• worsening of pre-existing curvature of the spine (scoliosis).
• middle ear infection, hearing or ear problems in patients with Turner syndrome.
• redness, itching and tissue weakness in the area of skin you inject.
• increase in phosphorus, alkaline phosphatase, and parathyroid hormone levels in your blood.

The most common side effects of Norditropin^® include:

• headaches, muscle pain, joint stiffness, high blood sugar (hyperglycemia), and sugar in your urine (glucosuria).

Please click here for Norditropin^® Prescribing Information.

Norditropin^® is a prescription medication.

Novo Nordisk provides patient assistance for those who qualify. Please call 1-866-310-7549 to learn more about Novo Nordisk assistance programs.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Talk to your healthcare provider and find out if Norditropin^® is right for you or your child.

Selected 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.
• Hypersensitivity: Patients with known hypersensitivity to somatropin or any of its excipients.
• Diabetic retinopathy: Patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed epiphysis: Children with closed epiphyses.

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.
• Hypersensitivity: Patients with known hypersensitivity to somatropin or any of its excipients.
• Diabetic retinopathy: Patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed epiphysis: Children with closed epiphyses.

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.
• Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products.
• Fluid retention: In adults, fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias), usually transient and dose-dependent, may occur frequently.
• Hypoadrenalism: Patients 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. In addition, 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, 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.