Somatropin (rDNA origin)

Pediatric Patients

Humatrope is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH).

Humatrope is indicated for the treatment of short stature associated with Turner syndrome [see Clinical Studies].

Humatrope is indicated for the treatment of idiopathic short stature, also called non-GH-deficient 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 for whom diagnostic evaluation excludes other causes of short stature that should be observed or treated by other means [see Clinical Studies]; SDS = standard deviation scores.

Humatrope is indicated for the treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency [see Clinical Studies].

Humatrope is indicated for the treatment of growth failure in children born small for gestational age (SGA) who fail to demonstrate catch-up growth by age two to four years [see Clinical Studies].

Adult Patients

Humatrope is indicated for the replacement of endogenous GH in adults with GH deficiency who meet either of the following two criteria [see Clinical Studies]:

Patients who have GH deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or

Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Patients who were treated with somatropin for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults. According to current standards, confirmation of the diagnosis of adult GH deficiency in both groups involves an appropriate GH provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic GH deficiency.

Your pharmacist can provide more information about somatropin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 12.01. Revision date: 8/10/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Move the site where you give the shot with each shot.
• Do not give into skin that is irritated, bruised, red, infected, or scarred.
• Do not shake the solution.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Wash your hands before and after use.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Feeling tired or weak.
• Muscle or joint pain.
• Muscle stiffness.
• Not able to sleep.
• Upset stomach or throwing up.
• Gas.
• Belly pain.
• Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about somatropin, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about somatropin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using somatropin.

Review Date: October 4, 2017

Clinical trials have demonstrated that TEV-TROPIN™ is equivalent in its therapeutic effectiveness and in its pharmacokinetic profile to those of human growth hormone of pituitary origin (somatropin). TEV-TROPIN™ stimulates linear growth in children who lack adequate levels of endogenous growth hormone. Treatment of growth hormone-deficient children with TEV-TROPIN™ produces increased growth rates and IGF-1 (Insulin-Like Growth Factor/Somatomedin-C) concentrations that are similar to those seen after therapy with human growth hormone of pituitary origin.

Both TEV-TROPIN™ and somatropin have also been shown to have other actions including:

1. Tissue Growth
   
   1. Skeletal Growth .  TEV-TROPIN™ stimulates skeletal growth in patients with growth hormone deficiency. The measurable increase in body length after administration of TEV-TROPIN™ results from its effect on the epiphyseal growth plates of long bones. Concentrations of IGF-1, which may play a role in skeletal growth, are low in the serum of growth hormone-deficient children but increase during treatment with TEV-TROPIN™. Mean serum alkaline phosphatase concentrations are increased.
   2. Cell Growth .  It has been shown that there are fewer skeletal muscle cells in short statured children who lack endogenous growth hormone as compared with normal children. Treatment with somatropin results in an increase in both the number and size of muscle cells.
   3. Organ Growth .  Somatropin influences the size of internal organs and it also increases red cell mass.
2. Protein Metabolism
   Linear growth is facilitated, in part, by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, results from treatment with somatropin.
3. Carbohydrate Metabolism
   Children with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with somatropin. Large doses of somatropin may impair glucose tolerance.
4. Lipid Metabolism
   Administration of somatropin to growth hormone-deficient patients mobilizes lipid, reduces body fat stores, and increases plasma fatty acids.
5. Mineral Metabolism
   Sodium, potassium, and phosphorous are conserved by somatropin. Serum concentrations of inorganic phosphates increased in patients with growth hormone deficiency after therapy with TEV-TROPIN™ or somatropin. Serum calcium concentrations are not significantly altered in patients treated with either somatropin or TEV-TROPIN™.
6. Connective Tissue Metabolism
   Somatropin stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.

See CONTRAINDICATIONS for information on increased mortality in patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or with acute respiratory failure. The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with growth hormone in patients having acute critical illnesses should be weighed against the potential risk.

There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstructions 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 growth hormone. If during treatment with growth hormone, 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 growth hormone 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 (see CONTRAINDICATIONS ).

Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, TEV-TROPIN™ is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Benzyl alcohol as a preservative in bacteriostatic normal saline, USP, has been associated with toxicity in newborns. When administering TEV-TROPIN™ to newborns, reconstitute with sterile normal saline for injection, USP. WHEN RECONSTITUTING WITH STERILE NORMAL SALINE, USE ONLY ONE DOSE PER VIAL AND DISCARD THE UNUSED PORTION.

The recommended dosage of up to 0.1 mg/kg (0.3 IU/kg) of body weight 3 times per week should not be exceeded. Acute overdose could cause initial hypoglycemia and subsequent hyperglycemia. Long-term repeated use of doses in excess of those recommended could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess human growth hormone.

A dosage of up to 0.1 mg/kg (0.3 IU/kg) of body weight administered 3 times per week by subcutaneous injection is recommended. The dosage schedule for TEV-TROPIN™ should be individualized for each patient. Subcutaneous injection of greater than 1 mL of reconstituted solution is not recommended.

After the dose has been determined, each vial of TEV-TROPIN™ should be reconstituted with 1 to 5 mL of bacteriostatic 0.9% sodium chloride for injection, USP (benzyl alcohol preserved). * The stream of normal saline should be aimed against the side of the vial to prevent foaming. Swirl the vial with a GENTLE rotary motion until the contents are completely dissolved and the solution is clear. DO NOT SHAKE. Since TEV-TROPIN™ is a protein, shaking or vigorous mixing will cause the solution to be cloudy. If the resulting solution is cloudy or contains particulate matter, the contents MUST NOT be injected.

Occasionally, after refrigeration, some cloudiness may occur. This is not unusual for proteins like TEV-TROPIN™ growth hormone. Allow the product to warm to room temperature. If cloudiness persists or particulate matter is noted, the contents MUST NOT be used.

Before and after injection, the septum of the vial should be wiped with rubbing alcohol or an alcoholic antiseptic solution to prevent contamination of the contents by repeated needle insertions. It is recommended that TEV-TROPIN™ be administered using sterile disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be drawn from the vial with reasonable accuracy.

STABILITY AND STORAGE

Before Reconstitution - Vials of TEV-TROPIN™ are stable when refrigerated at 36° to 46°F (2° to 8°C). Expiration dates are stated on the labels.

After Reconstitution - Vials of TEV-TROPIN™ are stable for up to 14 days when reconstituted with bacteriostatic 0.9% sodium chloride (normal saline), USP, and stored in a refrigerator at 36° to 46°F (2° to 8°C). Do not freeze the reconstituted solution.