Omnitrope

Omnitrope (somatropin) 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 injection (under the skin) and is available as a prefilled cartridge for use with the Omnitrope Pen delivery system, or as a powder for injection. Omnitrope is manufactured by Sandoz Inc.

Omnitrope works by binding to growth hormone receptors on target cells, triggering signals that produce a range of effects throughout the body. Some effects, such as bone growth and protein synthesis, are indirect and work through IGF-1, a protein released by the liver in response to the drug. Others, such as the breakdown of fat (lipolysis), result from somatropin acting directly on cells.

Omnitrope has been available in the United States since 2006. It was approved through the 505(b)(2) pathway, which allowed Sandoz to rely in part on the FDA's existing findings for an already approved somatropin product alongside its own comparative data. At the time, the United States had no dedicated approval pathway for biosimilars, and Omnitrope was the first product of its kind to reach the US market.

Omnitrope is FDA-approved to treat the following conditions:

In children

• Growth hormone deficiency (GHD). Children whose bodies produce too little or no growth hormone, causing growth failure
• Prader-Willi syndrome (PWS). A genetic condition causing poor muscle tone, low levels of sex hormones, and a constant feeling of hunger, which can also affect growth. Diagnosis must be confirmed by genetic testing before starting Omnitrope.
• 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
• Turner syndrome (TS). A chromosomal condition affecting girls that can cause short stature and other developmental differences
• Idiopathic short stature (ISS). Children who are significantly shorter than average (height standard deviation score of -2.25 or lower), with no identifiable medical cause, whose growth plates have not yet closed

In adults

• Growth hormone deficiency (GHD). Adults whose pituitary gland does not produce enough growth hormone, either due to pituitary or hypothalamic disease, surgery, radiation, trauma, or a deficiency that began in childhood.

Do not use Omnitrope if you have:

• An 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 (in children). Somatropin should not be used in patients with Prader-Willi Syndrome 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 when somatropin was used in such patients.
• 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.
• Diabetic retinopathy: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed epiphyses: Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.
• Hypersensitivity: Omnitrope 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 somatropins.

Before starting Omnitrope, tell your doctor if you or your child has:

• A history of cancer, especially during childhood
• Diabetes or pre-diabetes
• Breathing problems or sleep apnea
• A pituitary gland disorder
• Abnormal curvature of the spine (scoliosis)
• Underactive thyroid (hypothyroidism)
• A head injury or brain tumor
• Received radiation treatment to the brain or head as a child
• Liver or kidney disease
• High blood pressure
• Pancreatitis (inflammation of the pancreas).

Important note about benzyl alcohol:Some presentations of Omnitrope (the 5 mg cartridges and 5.8 mg vial) contain benzyl alcohol, which can cause serious side effects or death in very young or premature babies. Do not give these presentations to a newborn or premature infant.

Pregnancy and Omnitrope

There is not enough data on somatropin use in pregnancy to know whether it affects a developing baby. In animal studies at roughly 19 to 24 times human treatment levels, there was no evidence of harm to the fetus or newborn, though animal findings do not always predict what happens in people. Somatropin should be used in pregnancy only if clearly needed. Tell your doctor if you are pregnant or planning to become pregnant.

Breastfeeding and Omnitrope

It may not be safe to breastfeed while using Omnitrope. Talk to your doctor about the risks before breastfeeding.

Omnitrope in older adults and in kidney or liver disease

Omnitrope has not been studied in people aged 65 and over. Older adults may be more sensitive to somatropin and more likely to get side effects, so the label advises a lower starting dose and smaller increases. Being older or carrying more weight both make fluid retention side effects more likely early in treatment.

No pharmacokinetic studies have been done with Omnitrope in people with reduced kidney or liver function, so there is no dedicated dosing guidance for them.

Monitoring and tests during Omnitrope treatment

• Eye examinations. A fundoscopic examination is recommended when treatment starts and periodically afterward, to check for swelling of the optic nerve.
• Blood glucose. Checked periodically in everyone, and more closely in people with diabetes, prediabetes or risk factors for diabetes.
• Thyroid function tests. Done periodically, with thyroid hormone replacement started or adjusted if needed.
• IGF-1 levels. Used alongside clinical response to guide dose changes, and the dose is reduced if IGF-1 rises above the normal range for the person's age and sex.
• Other blood tests. Inorganic phosphorus, alkaline phosphatase and parathyroid hormone can all rise during treatment.
• Before starting, in Prader-Willi syndrome. Children are assessed for upper airway obstruction and sleep apnea. Treatment is interrupted if signs of airway obstruction, including new or increased snoring, or new sleep apnea appear.
• In Turner syndrome. Ears are checked for otitis media and other ear problems, and blood pressure and heart health are monitored.
• Growth in children. If growth rate fails to increase, particularly in the first year, the prescriber will check adherence and look for other causes such as low thyroid levels, undernutrition, advanced bone age or antibodies to growth hormone.

How common are Omnitrope side effects?

Children

These are the side effects reported in 5% or more of children with growth hormone deficiency in the studies of Omnitrope itself.

Adults

Omnitrope has not been studied on its own in adults. The adult side effect data in the label comes from trials of another somatropin product in 1,145 adults. Most side effects were mild to moderate signs of fluid retention, appeared early in treatment, and either settled on their own or improved when the dose was reduced. In the first 6 months, the ones reported significantly more often than with placebo were swelling of the hands and feet (17.5% versus 5.1%), joint pain (17.3% versus 4.2%), pain in the arms or legs (14.7% versus 5.9%), swelling of the lower legs (10.8% versus 2.6%), tingling or numbness (9.6% versus 1.9%) and stiffness in the arms or legs (7.9% versus 1.6%).

In longer extension studies of the same comparator product, 2% of 3,031 adults developed carpal tunnel syndrome, which eased after a dose reduction, a break in treatment or surgery, and 0.4% developed diabetes, all of whom had risk factors beforehand.

Omnitrope may cause the following serious side effects:

• 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.
• Prader-Willi Syndrome in Children: There have been reports of fatalities 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 of sleep apnea, treatment should be interrupted.
• Neoplasms: An increased risk of a second neoplasm has been reported for childhood cancer survivors treated with somatropin for GH deficiency who developed following radiation to the brain/head. Intracranial tumors, in particular meningiomas, were the most common of these. The relationship between somatropin therapy and CNS tumor recurrence in adults is unknown. Monitor for progression or recurrence in patients receiving somatropin therapy who have a history of GH deficiency secondary to an intracranial neoplasm. Thoroughly consider the risks and benefits of starting somatropin in children at increased risk for developing malignancies due to certain rare genetic causes of short stature. These patients should be carefully monitored for the development of neoplasms. Any pre-existing nevi should be monitored carefully for increased growth or potential malignant changes.
• Impaired 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.
• Intracranial Hypertension: Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting have been reported in a small number of patients treated with somatropins. Fundoscopic examination is recommended at the initiation of and periodically during therapy. If papilledema is observed by fundoscopy during treatment with somatropin, treatment should be stopped, and the patient’s condition should be reassessed before treatment is resumed. Patients with Turner Syndrome and Prader-Willi Syndrome may be at increased risk for the development of intracranial hypertension.
• Hypersensitivity: Serious systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported with postmarketing use of somatropins. 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 frequently occur.
• Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism.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: Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders and in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during Omnitrope therapy should be evaluated for slipped capital femoral epiphysis and osteonecrosis and managed accordingly.
• Progression of Scoliosis in Pediatric Patients: Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis.
• Otitis Media and Cardiovascular Disorders in Patients with Turner Syndrome: Patients with Turner Syndrome 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 (e.g., stroke, aortic aneurysm or dissection, hypertension) as they are at increased risk for these conditions.
• Lipoatrophy: Injection site should be rotated to avoid tissue atrophy.
• Laboratory Tests: Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and IGF-1 may increase after 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 Turner Syndrome may be at greater risk than other somatropin-treated children.
• Benzyl Alcohol: Benzyl alcohol, an ingredient in Omnitrope Cartridge 5 mg/1.5 mL and the diluent for Omnitrope for injection 5.8 mg/vial, has been associated with serious adverse events and death, particularly in pediatric patients, and should not be used in premature babies or neonates. Consider the combined daily metabolic load of benzyl alcohol from all sources.
• Pregnancy: Somatropin should be used during pregnancy only if clearly needed and with caution in nursing mothers because there are limited available data on somatropin use in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
• Lactation: There is no information regarding the presence of somatropin in human milk. Limited published data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone. No adverse effects related to somatropin in the breastfed infant have been reported. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Omnitrope and any potential adverse effects on the breastfed infant from Omnitrope or from the underlying maternal condition.
• Special Populations: The safety and effectiveness of somatropin in patients aged 65 years and over have not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of somatropin and may be more prone to adverse reactions.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Omnitrope was compared against another approved somatropin product in 89 children with growth hormone deficiency, each given 0.03 mg/kg daily. Growth was similar with both.

Children who started on the comparator product and switched to the Omnitrope cartridge at 9 months had almost identical results, at 10.7 cm/year and then 8.6 cm/year.

Omnitrope's approval for Prader-Willi syndrome, small for gestational age, Turner syndrome, idiopathic short stature and adult growth hormone deficiency rests on trials of other somatropin products rather than on trials of Omnitrope itself.

How well does Omnitrope work for the other conditions?

Omnitrope's approval for Prader-Willi syndrome, small for gestational age, Turner syndrome and idiopathic short stature rests on trials of other somatropin products rather than on trials of Omnitrope itself. The results below come from those trials and appear in the Omnitrope label.

In idiopathic short stature, 69% of children on the higher dose gained at least a full standard deviation of height, compared with 50% on the lower dose and 10% of untreated children.

In Prader-Willi syndrome, treatment also changed body composition rather than height alone. Over 12 months, treated children lost an average of 0.9 kg of fat and gained 4.7 kg of lean body mass, while untreated children gained 2.3 kg of fat and 0.7 kg of lean mass.

How long does Omnitrope take to work?

Growth is measured over months, not weeks. In the Omnitrope trial in children with growth hormone deficiency, growth rate went from 3.8 cm/year before treatment to 10.7 cm/year over the first 9 months, then settled to 8.5 cm/year by 15 months. The fastest growth happens in the first year and the rate eases after that, which is expected and does not mean the medicine has stopped working.

Prescribers usually check height, IGF-1 levels and bone age at intervals through the first year. If growth has not picked up, the label directs them to look at whether doses are being given as prescribed, and at other explanations such as an underactive thyroid, poor nutrition, advanced bone age, or antibodies to growth hormone.

Adults treated for growth hormone deficiency are not being treated to grow taller. Treatment aims at body composition, and changes there are gradual.

Omnitrope is injected subcutaneously (under the skin).

• The weekly dose is divided into 6 or 7 daily injections.
• Your doctor will determine the right dose based on your condition, body weight, and response to treatment.
• Always rotate injection sites to prevent skin changes (lipoatrophy) at the same spot.
• Inject into the thigh, buttocks, or stomach area (abdomen). Do not inject near your belly button (navel) or waistline.

Omnitrope presentations and pack sizes

The cartridges and pens are not interchangeable. A 5 mg cartridge goes only in the Pen 5 and a 10 mg cartridge only in the Pen 10, because the pens deliver different dose increments. Cartridges are single-patient-use, and a pen should never be shared even with a new needle.

Omnitrope dosing for children

• Growth hormone deficiency: 0.16 to 0.24 mg/kg/week, divided into 6 to 7 daily injections
• Prader-Willi syndrome: 0.24 mg/kg/week, divided into 6 to 7 daily injections
• Small for gestational age (SGA): up to 0.48 mg/kg/week, divided into 6 to 7 daily injections
• Turner syndrome: 0.33 mg/kg/week, divided into 6 to 7 daily injections
• Idiopathic short stature: up to 0.47 mg/kg/week, divided into 6 to 7 daily injections.

Treatment is stopped when the bone growth plates have closed. Children who received Omnitrope for growth hormone deficiency during childhood and whose growth plates have closed should be reassessed before continuing treatment at an adult dose.

Omnitrope dosing for adults

• Starting dose (weight-based): no more than 0.04 mg/kg/week given as daily injections
• Dose adjustment: increased at 4 to 8 week intervals as tolerated, up to a maximum of 0.08 mg/kg/week
• Alternative non-weight-based starting dose: approximately 0.2 mg/day (range 0.15 to 0.30 mg/day), increased gradually every 1 to 2 months by 0.1 to 0.2 mg/day increments.

Older patients and those who are obese are more prone to side effects and should start on lower doses. Women taking oral estrogen replacement may need higher doses than men, as oral estrogen reduces the body's response to growth hormone.

Omnitrope delivery devices

Omnitrope is available in two forms: a prefilled cartridge solution (5 mg/1.5 mL or 10 mg/1.5 mL) for use with the Omnitrope Pen 5 or Pen 10, and a 5.8 mg lyophilized (freeze-dried) powder in a vial for reconstitution.

• The 5 mg cartridge must only be used with the Pen 5, and the 10 mg cartridge must only be used with the Pen 10.
• Follow the instructions for use provided with your device.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up for a missed dose. 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. Symptoms of Omnitrope overdose include tremors or shaking, cold sweats, increased hunger, headache, drowsiness, weakness, dizziness, fast heartbeat, and nausea. Long-term overdose may cause excessive growth.

• Do not inject Omnitrope into the same site twice in a row — always rotate injection sites
• Do not shake the medicine — shaking can damage the protein
• Do not use Omnitrope if the solution has changed color or contains particles
• Do not stop taking any steroid medicine suddenly or change doses without your doctor's advice
• Do not share your Omnitrope Pen with anyone else, even if you have changed the needle. Sharing the pen can pass an infection to them or from them to you.

Omnitrope is a specialty medicine and is usually dispensed through a specialty pharmacy rather than a retail counter. What you pay depends on the strength, the number of cartridges in the pack, and your insurance, and growth hormone is commonly subject to prior authorization.

Sandoz runs a self-pay program for people paying without insurance. Coverage rules, copay assistance and patient assistance programs change, so check current terms before relying on them.

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

• Glucocorticoids (steroids such as prednisone, dexamethasone, methylprednisolone). Pharmacologic doses of glucocorticoids can reduce the growth-promoting effects of somatropin. People taking glucocorticoid replacement for adrenal insufficiency may need their dose increased after starting Omnitrope, as somatropin affects cortisol metabolism.
• Cytochrome P450-metabolized drugs. Somatropin may alter the clearance of drugs broken down by liver enzymes. Careful monitoring is advised.
• Oral estrogen. Women taking oral estrogen replacement may need higher Omnitrope doses, as oral estrogen reduces the response to growth hormone.
• Insulin and diabetes medicines. Omnitrope 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 Omnitrope; tell your doctor if you are taking these.

This list is not complete. Other drugs may interact with somatropin. Not all possible interactions are listed here.

Store Omnitrope cartridges and vials in a refrigerator at 36°F to 46°F (2°C to 8°C), in the original carton to protect them from light. Do not freeze.

Omnitrope stays refrigerated throughout. Unlike some other growth hormone pens, an Omnitrope cartridge that is already in use is not given a room temperature allowance in the label: once the pen is in use it goes back in the refrigerator, in its original carton, between doses. Do not freeze it, and keep it out of the freezer compartment and away from the cooling element in a travel cooler.

Once a cartridge is in use, leave it in the pen and keep the pen in its original carton in the refrigerator. Discard any medicine left in a cartridge after 28 days, and any left in a vial 21 days after it was mixed.

When mixing the powder, swirl the vial gently. Do not shake it, as shaking can damage the growth hormone protein. Do not inject Omnitrope if the solution is cloudy or contains particles. It should be clear and colorless.

Omnitrope ingredients

Active ingredient: somatropin, a 191-amino acid recombinant human growth hormone produced in Escherichia coli, with a molecular weight of approximately 22,125 daltons.

The three Omnitrope presentations do not share the same inactive ingredients. The 5 mg cartridge is preserved with benzyl alcohol and the 10 mg cartridge with phenol.

Omnitrope is manufactured by Sandoz Inc. To report side effects or for product information, call Sandoz at 1-800-525-8747.