Norditropin

Norditropin is a recombinant human growth hormone used to treat growth failure in children and growth hormone deficiency in adults. It is given as a subcutaneous (under the skin) daily injection using the Norditropin FlexPro prefilled pen. Norditropin is a prescription injection manufactured by Novo Nordisk.

Norditropin (somatropin) is a man-made form of human growth hormone, identical in structure to the growth hormone produced naturally by the body. It works by replacing missing growth hormone, stimulating bones, muscles, and other tissues to grow.

Norditropin gained FDA approval on June 20, 2000. Somatropin was originally approved in 1987.

Norditropin is FDA-approved to treat the following conditions:

In children

• Growth hormone deficiency (GHD). Children who are not growing normally because their body produces too little or no growth hormone
• Noonan syndrome. A genetic condition that can cause short stature, heart problems, and other developmental differences
• Turner syndrome. A chromosomal condition affecting girls that can cause short stature and other developmental differences
• Small for gestational age (SGA) with no catch-up growth. Children born smaller than expected who have not caught up in height by age 2 to 4 years
• Idiopathic short stature (ISS). Children who are significantly shorter than average (height standard deviation score below -2.25) with no identifiable medical cause, whose bone growth plates have not yet closed
• Prader-Willi syndrome (PWS). A genetic condition causing poor muscle tone, low sex hormone levels, and constant hunger, which can also affect growth. Diagnosis must be confirmed by genetic testing before starting Norditropin.

In adults

• Growth hormone deficiency (GHD). Adults whose pituitary gland does not produce enough growth hormone, whether the deficiency began in childhood or developed in adulthood.

Read the detailed Instructions for Use that come with Norditropin FlexPro pen.

Norditropin is injected subcutaneously (under the skin) daily into the abdomen, buttocks, upper thighs, or the back of the upper arms. Rotate the injection site each day to prevent lipoatrophy (fat loss under the skin). A healthcare provider will show you how to use the FlexPro pen before you start.

Norditropin treatment should be supervised by a physician experienced in the diagnosis and management of growth disorders. Doses are individualised based on body weight and treatment response.

Do not use Norditropin if you or your child:

• Are critically ill following heart or abdominal surgery, trauma, or serious breathing problems
• Are a child with Prader-Willi syndrome who is severely obese or has breathing problems including sleep apnea
• Have active cancer or a tumor
• Have active proliferative or severe non-proliferative diabetic retinopathy (certain eye complications of diabetes)
• Are a child with closed bone growth plates (epiphyses)
• Are allergic to somatropin or any ingredient in Norditropin

Before starting Norditropin, tell your doctor if you or your child:

• Have had cancer, a brain tumor, or radiation treatment, especially during childhood
• Have diabetes or pre-diabetes
• Have breathing problems or sleep apnea
• Have a pituitary gland disorder
• Have a history of scoliosis
• Have underactive thyroid (hypothyroidism)
• Have had a head injury
• Are pregnant or intending to become pregnant
• Are breastfeeding or intending to breastfeed.

A fundoscopic eye examination should be performed before starting treatment to rule out pre-existing papilledema (swelling of the optic nerve).

Pregnancy and Norditropin

It is not known whether Norditropin will harm an unborn baby. Tell your doctor if you are pregnant or planning to become pregnant before starting treatment.

Breastfeeding and Norditropin

It is not known whether Norditropin passes into breast milk, though limited published data suggest exogenous somatropin does not increase breastmilk growth hormone concentrations. You and your healthcare provider should weigh the benefits and risks before breastfeeding while on this medication.

Common side effects

The most common Norditropin side effects include:

• Headache
• Muscle pain (myalgia)
• Joint stiffness or pain (arthralgia)
• High blood sugar (hyperglycemia)
• Sugar in the urine (glucosuria)
• Swelling or rapid weight gain
• Numbness or tingling
• Stomach pain or gas
• Back pain
• Cold or flu symptoms — stuffy nose, sneezing, sore throat, ear pain
• Pain, itching, skin changes, or loss of fat tissue at the injection site
• Upper respiratory tract infections
• Fever and ear infections (particularly in children)

In the adult GHD clinical trial, peripheral edema (swelling) was reported in 42% of Norditropin-treated patients compared to 8% in the placebo group, and was the most frequently reported side effect. This is usually transient and dose-dependent.

Other side effects reported during post-approval use include enlarged breast tissue in males (gynecomastia).

This is not a complete list of side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or to Novo Nordisk at 1-888-668-6444.

Increased risk of death in critical illness

Norditropin must not be used in people who are critically ill following open-heart surgery, abdominal surgery, multiple trauma, or acute respiratory failure. Two clinical trials found a significantly higher mortality rate (42% versus 19%) in critically ill patients treated with pharmacologic doses of somatropin compared to placebo.

Sudden death in children with Prader-Willi syndrome

There have been reports of sudden death in children with Prader-Willi syndrome who started growth hormone therapy and 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 may be at greater risk than females. Children with Prader-Willi syndrome must be assessed for upper airway obstruction and sleep apnea before starting treatment. Call your doctor right away if your child develops shortness of breath, coughing, or new or increased snoring.

Cancer and tumors

Norditropin may stimulate the growth of existing tumors and should not be started until any active malignancy is fully treated and in remission. Children who received radiation to the brain or head for a first cancer and later developed growth hormone deficiency have a higher risk of a second tumor, particularly meningiomas. All patients on Norditropin should be monitored for tumor recurrence and should report changes in behavior, new headaches, vision disturbances, or changes in the size or appearance of moles.

High blood sugar and diabetes

Norditropin can reduce insulin sensitivity, particularly at higher doses. New onset type 2 diabetes has been reported in patients taking somatropin. Blood glucose will be monitored during treatment, and doses of insulin or diabetes medicines may need to be adjusted. People at higher risk include those with obesity, Turner syndrome, or a family history of diabetes.

Increased pressure in the skull (intracranial hypertension)

A build-up of pressure inside the skull has been reported in a small number of patients treated with somatropin, usually within the first 8 weeks of starting treatment. Symptoms typically resolve after stopping treatment or reducing the dose. A fundoscopic eye examination is required before starting Norditropin and periodically during treatment. Patients with Turner syndrome may be at increased risk. Contact your healthcare provider immediately if you or your child develops severe headaches, vision changes, nausea, or vomiting.

Serious allergic reactions

Serious allergic reactions including anaphylaxis and angioedema have been reported. Get emergency medical help immediately if you or your child develops swelling of the face, lips, mouth, or tongue; trouble breathing; wheezing; severe itching; skin rashes, redness, or swelling; dizziness or fainting; or a fast or pounding heartbeat.

Fluid retention

Fluid retention during Norditropin treatment in adults may occur frequently. Symptoms include swelling in the hands and feet, joint or muscle pain, and nerve compression symptoms such as pain, burning, or tingling in the hands, arms, or legs (carpal tunnel syndrome). These effects are usually transient and dose-dependent. Tell your healthcare provider if you develop these symptoms.

Low cortisol (hypoadrenalism)

Norditropin can lower cortisol levels, particularly in people who already have or are at risk for pituitary hormone deficiencies. People taking glucocorticoid replacement therapy may need their dose increased after starting Norditropin. Symptoms include darkening of the skin, extreme fatigue, dizziness, weakness, and weight loss.

Low thyroid hormone (hypothyroidism)

Norditropin can cause or worsen hypothyroidism, which may reduce how well treatment works. Patients with Turner syndrome have an increased risk of developing autoimmune thyroid disease. Periodic thyroid function tests are required, and thyroid hormone replacement will be started or adjusted if needed.

Slipped capital femoral epiphysis in children

Children treated with growth hormone, particularly those with endocrine disorders, including growth hormone deficiency and Turner syndrome, may develop a condition where the thigh bone slips at the hip joint. This can lead to osteonecrosis (bone tissue death due to reduced blood supply) if not treated promptly. Contact your healthcare provider immediately if your child develops a limp or complains of hip or knee pain.

Worsening scoliosis in children

Norditropin increases the growth rate, which can cause pre-existing curvature of the spine (scoliosis) to worsen in children who experience rapid growth. Norditropin has not been shown to cause scoliosis, but children with a history of scoliosis will be monitored during treatment.

Pancreatitis

Cases of pancreatitis (inflammation of the pancreas) have been reported in both children and adults receiving somatropin, with a potentially greater risk in children. Girls with Turner syndrome may be at higher risk than other pediatric patients. Tell your healthcare provider about any new or persistent severe abdominal pain.

Lipoatrophy

Repeatedly injecting Norditropin into the same area can cause loss of fat tissue under the skin at that site. Rotating the injection site with each daily dose reduces this risk.

Norditropin is a recombinant human growth hormone, a laboratory-made protein that is identical in structure to the growth hormone produced naturally by the pituitary gland. It works by binding to growth hormone receptors on target cells, triggering signals that stimulate growth and metabolism.

Some of its effects work through a protein called insulin-like growth factor-1 (IGF-1) produced by the liver, which promotes bone growth, protein synthesis, and skeletal development. Other effects, such as the breakdown of fat (lipolysis), result from somatropin acting directly on cells. In children with growth hormone deficiency, Norditropin stimulates the growth plates (epiphyses) of long bones, increasing height velocity.

Norditropin dosing for children

• Growth hormone deficiency: 0.17 to 0.24 mg/kg/week (0.024 to 0.034 mg/kg/day) subcutaneously, given 6 to 7 days per week
• Noonan syndrome: up to 0.46 mg/kg/week (up to 0.066 mg/kg/day) subcutaneously
• Turner syndrome: up to 0.47 mg/kg/week (up to 0.067 mg/kg/day) subcutaneously
• Small for gestational age (SGA): up to 0.47 mg/kg/week (up to 0.067 mg/kg/day) subcutaneously
• Idiopathic short stature: up to 0.47 mg/kg/week (up to 0.067 mg/kg/day) subcutaneously
• Prader-Willi syndrome: 0.24 mg/kg/week (0.034 mg/kg/day) subcutaneously.

The weekly dose is divided into 6 or 7 equal daily injections. Treatment is stopped when the bone growth plates close. Children who were treated with Norditropin for growth hormone deficiency during childhood and whose growth plates have closed should be reassessed before continuing treatment at an adult dose.

Norditropin dosing for adults

Two dosing approaches may be used:

• Non-weight-based (preferred): Start at approximately 0.2 mg/day (range 0.15 to 0.30 mg/day) subcutaneously and increase every 1 to 2 months by 0.1 to 0.2 mg/day according to individual response and IGF-1 levels
• Weight-based (not recommended for obese patients): Start at 0.004 mg/kg/day subcutaneously and increase as tolerated to a maximum of 0.016 mg/kg/day.

Older patients are more prone to side effects and should start on lower doses with smaller increments. Women taking oral estrogen replacement may need higher doses, as oral estrogen reduces the response to growth hormone.

Norditropin FlexPro pen strengths

• 5 mg/1.5 mL (orange pen)
• 10 mg/1.5 mL (blue pen)
• 15 mg/1.5 mL (green pen)
• 30 mg/3 mL (purple pen)

Norditropin FlexPro pens are for use by one person only. Do not share your pen or needles with another person, even if the needle has been changed.

Take the missed dose as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and continue your regular schedule. Do not take two doses to make up for a missed one. Call your doctor if you miss more than 3 doses in a row.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Short-term overdose can initially cause low blood sugar (hypoglycemia), then high blood sugar (hyperglycemia). Norditropin overdose is also likely to cause fluid retention. Long-term overdose may result in signs of gigantism (in children) or acromegaly (in adults), consistent with the known effects of excess growth hormone.

• Do not inject into the same site two days in a row; always rotate injection sites
• Do not shake the medicine; this can damage the protein
• Do not use Norditropin if the solution looks cloudy or contains particles
• Do not stop taking any steroid medicines suddenly or change doses without your doctor's advice.

Tell your doctor about all medicines, vitamins, and supplements you take. Norditropin has the following clinically important interactions:

• Glucocorticoids (steroids such as prednisone, dexamethasone, methylprednisolone). People taking glucocorticoid replacement for adrenal insufficiency may need their dose increased after starting Norditropin, as somatropin inhibits an enzyme involved in cortisol metabolism. In children, pharmacologic glucocorticoid doses may reduce the growth-promoting effects of Norditropin; glucocorticoid replacement dosing should be carefully adjusted to avoid both hypoadrenalism and growth inhibition.
• Cytochrome P450-metabolized drugs. Norditropin may alter the clearance of drugs broken down by liver enzymes. Careful monitoring is advised when these medicines are used together.
• Oral estrogen. Women taking oral estrogen replacement may need higher Norditropin doses, as oral estrogen reduces the IGF-1 response to growth hormone.
• Insulin and diabetes medicines. Norditropin can reduce insulin sensitivity. Doses of insulin or oral diabetes medicines may need adjustment after starting treatment.
• Birth control pills or hormone replacement therapy. May interact with Norditropin; tell your doctor if you are taking these.

This list is not complete. Other drugs may interact with Norditropin, including prescription and over-the-counter medicines, vitamins, and herbal products.

Before first use (unused pen)

• Store in a refrigerator at 36°F and 46°F (2°C and 8°C)
• Do not store directly next to the refrigerator cooling element
• Do not freeze. Do not use Norditropin if it has been frozen
• Keep away from direct light
• Do not use after the expiration date on the carton or pen
• Do not use Norditropin if stored in temperatures warmer than 77°F (25°C)

After first use (in-use pen)

• Store in the refrigerator at 36°F and 46°F (2°C and 8°C) and use within 4 weeks, or
• Store at room temperature, no warmer than 77°F (25°C) and use within 3 weeks

Keep Norditropin and all medicines out of the reach of children.

Active ingredient: somatropin (recombinant human growth hormone)

Inactive ingredients: histidine, mannitol, phenol, poloxamer 188, hydrochloric acid/sodium hydroxide (as needed to adjust pH), water for injection USP

Norditropin is manufactured by Novo Nordisk Inc., Plainsboro, NJ 08536. For more information, visit norditropin.com or call 1-888-668-6444.