Full Prescribing Information

Nutropin® [somatropin (rDNA origin) for injection] is produced by Genentech using recombinant DNA technology and has the same amino acid sequence as human growth hormone produced naturally in the human body. Recombinant growth hormone was cloned by Genentech scientists in 1979.

Indication: Nutropin® [somatropin (rDNA origin) for injection] and Nutropin AQ® [somatropin (rDNA origin) injection] are human growth hormone, available by prescription only. Doctors prescribe Nutropin therapy for children and teenagers who are short or growing slowly because they:

• Do not make enough growth hormone on their own
• Have idiopathic short stature, which means they are shorter than 98.8% of other children of the same age and sex; are growing at a rate not likely to allow them to reach normal adult height; and no other cause of short stature can be found
• Have Turner syndrome
• Have chronic kidney disease (CKD) up to the time of kidney transplant

Doctors prescribe Nutropin therapy for adults who have growth hormone deficiency that began either in:

• Adulthood as a result of pituitary disease, diseases of the hypothalamus, surgery, radiation therapy, or trauma; or
• Childhood. Patients treated for growth hormone deficiency in childhood, whose bones have stopped growing, should be reevaluated to see if they need to continue with growth hormone therapy

A patient’s doctor will test to see if growth hormone is right for them.

Status

• In November 1993, Genentech received U.S. Food and Drug Administration (FDA) approval for the treatment of growth failure associated with chronic renal insufficiency up to the time of renal transplantation in conjunction with optimal management of chronic renal insufficiency.
• In March 1994, Genentech received FDA approval for the long-term treatment of growth failure due to lack of adequate endogenous growth hormone secretion for pediatric patients. Nutropin becomes the first growth hormone product to receive FDA approval for two indications.
• In December 1996, Genentech received FDA approval for the long-term treatment of short stature associated with Turner syndrome.
• In December 1997, Genentech received FDA approval for the replacement of endogenous growth hormone in patients with adult growth hormone deficiency who have a biochemical diagnosis of adult GH deficiency and either adult- or child- onset GH deficiency.
• In June 2005, Genentech received FDA approval for the long-term treatment of idiopathic short stature defined by height 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.

Disease Education Growth hormone deficiency, GHD, is a pituitary disorder resulting in short stature and other physical ailments. GHD occurs when the production of growth hormone, secreted by the pituitary gland, is disrupted. Since growth hormone plays a critical role in stimulating body growth and development, and is involved in the production of muscle protein and in the breakdown of fats, a decrease in the hormone affects numerous body processes.

Turner syndrome affects approximately one in 2,500 female, live births. Turner syndrome is a chromosomal disorder that affects females exclusively and is characterized, in part, by short stature and ovarian dysfunction. It is caused by the absence of all or part of one of the X chromosomes.

Chronic renal insufficiency, CRI, affects about 3,000 children in the United States. It manifests through a gradual and progressive loss of the ability of the kidneys to excrete wastes, concentrate urine, and conserve electrolytes. Kidney transplants can help a child start growing normally again, but most children do not make up the growth lost prior to transplantation.

Idiopathic short status (ISS), also called non-growth hormone-deficient short stature, is a condition caused by unknown reasons after a thorough diagnostic evaluation by an endocrine specialist. Children in this category are generally healthy; their ISS diagnosis is usually arrived at when other potential underlying causes are ruled out and the patient does not meet the strict criteria defined for growth hormone deficiency.

NUTROPIN THERAPY IS NOT FOR:

• Patients having serious complications after undergoing open heart surgery, abdominal surgery, serious injuries involving many body systems, or life-threatening breathing problems. Deaths have been reported in such cases.
• Children who have Prader-Willi syndrome (PWS) and are very overweight or have a history of severe breathing problems. Deaths have been reported in children with PWS who are very overweight, have a history of blocked upper airways, sleep apnea (pauses in breathing during sleeping), or other severe breathing problems.
• Patients who have active cancer. Because growth hormone deficiency can be an early sign of some tumors in the brain or pituitary gland, the presence of these types of tumors should be ruled out by a doctor before patients start Nutropin therapy.
• Adults or children with certain types of eye disease caused by diabetes
• Children and teenagers whose bones have finished growing
• Patients who are allergic to somatropin, the active ingredient in Nutropin therapy. Reactions at the injection site are the most common allergic reactions.
• Patients with a known sensitivity to benzyl alcohol, an ingredient in the liquid used to mix Nutropin powder for injection. Sterile water should be used when mixing Nutropin for newborns.

Patients must tell their doctor before starting Nutropin therapy:

• If they take cyclosporine, hormone replacement therapy, insulin or other diabetes medications, drugs containing steroids, or drugs for seizures. These medications may need to be adjusted during Nutropin therapy.
• If they have pre-existing tumors or growth hormone deficiency caused by abnormal tissue in the brain. If so, patients should be watched closely for the worsening or return of this condition. If patients had cancer as a child, an increased risk of a new tumor, particularly certain brain tumors, has been reported in patients taking Nutropin therapy.
• If patients have diabetes, risk factors for diabetes, or impaired glucose tolerance. If so, their doctor should monitor their blood sugar closely during Nutropin therapy. New cases of type 2 diabetes have been reported in patients taking Nutropin therapy.
• If patients have hypopituitarism (an inability of the pituitary gland to produce sufficient hormones) and are on standard hormone replacement therapy. In that case, their doctor should monitor their hormone replacement therapy closely while they are taking Nutropin therapy.
• If they are pregnant, nursing, or plan to become pregnant. It is not known whether Nutropin is excreted in human milk. Nutropin therapy should be used during pregnancy only when clearly needed.

While taking Nutropin, patients must contact their doctor immediately if they experience:

• Changes in vision, a bad headache, or nausea with or without vomiting. This may be a sign of increased pressure in the brain.
• A limp or have hip or knee pain
• A fracture in the ball of the hip joint can occur in children who have endocrine problems and in children who have rapid growth.
• Children with growth failure due to CKD should be examined periodically for evidence of loss of bone minerals. Hip x-rays should be taken before starting Nutropin therapy in these children.
• Progression of scoliosis (curvature of the spine) that can occur in children who have rapid growth. Nutropin therapy has not been shown to increase the occurrence of this condition
• Any allergic reaction they experience to the injection of Nutropin therapy
• Abdominal pain. Cases of pancreatitis (inflammation of the pancreas) have been reported rarely in children and adults receiving Nutropin therapy.

Other important information about Nutropin:

• Adults may retain water during Nutropin therapy. This may be brief but may increase with higher doses of Nutropin therapy.
• Patients should have their thyroid function tested periodically during Nutropin therapy. Thyroid hormone treatment may need to be started or adjusted.
• Patients should be sure to inject Nutropin at a different recommended place on their body each time to avoid tissue breakdown. A doctor or nurse should provide injection training and supervise the first injection.
• The use of Nutropin therapy has not been studied in patients over 65 years of age. Elderly patients may be more sensitive to Nutropin therapy and may experience more side effects
• Patients with Turner syndrome should be monitored closely by a doctor for ear infections and cardiovascular problems during Nutropin therapy.
• Nutropin therapy may affect the body’s ability to process two hormones, cortisol and cortisone, which can lead to a condition called hypoadrenalism (under activity of the adrenal gland). In that case, glucocorticoid replacement therapy may need to be prescribed.

Common side effects reported in adults and children taking Nutropin therapy include injection site reactions. Additional common side effects in adults include swelling, joint pain, and carpal tunnel syndrome.

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

For additional important safety information, including the full prescribing information, please visit www.nutropin.com.