Belitropina ®

Hormones are messengers

Hormones are chemical “messengers” produced in one part of the body that travel to another part of the body to create some sort of change.

Special cells in glands and other organs produce hormones and release them into the body at specific times for specific reasons, depending upon the type of hormone. The hormones’ job is to tell parts of the body to do certain things. They travel through the bloodstream to their “target organ” or tissue, where they exert their effect by giving their instructions.

Growth hormone tells the body to grow

What is growth hormone? Growth hormone is made in the pituitary gland, which is located at the base of the brain. It does a lot more than just make a child grow taller; it’s responsible for the growth of the body, including organs and bones, and it helps the body’s metabolic processes.

When growth hormone is released from the pituitary gland, it “tells” the liver to release a second hormone, called insulin-like growth factor-1 (IGF-1).

Together, growth hormone and IGF-1 tell the bones, muscles, and other organs and tissues to grow by adding more cells.

What Belitropina ® does

In people with growth hormone deficiency, Belitropina® (somatropin [rDNA origin] injection) replaces the growth hormone that the body isn’t making.

Hormones are messengers

Pediatric Growth Hormone Deficiency Pediatric growth hormone deficiency (PGHD) occurs when the production of growth hormone is disrupted during infancy or childhood.

 

Growth hormone (often designated as hGH or GH) is secreted by the pituitary gland and plays a critical role in stimulating body growth and development. It is involved in the production of muscle protein and in the breakdown of fats. Decreased levels of growth hormone may result in abnormalities of many body processes, including growth and development, production of muscle protein, and breakdown of fats.

Although PGHD is uncommon, it may occur at any time during infancy or childhood, and there are many possible causes. Some involve damage to the pituitary gland or the hypothalamus, a part of the brain that controls the pituitary. A major sign of PGHD is a marked slowing of growth, usually to less than 2 inches (5 cm) a year.

Pediatric growth hormone deficiency is diagnosed through special blood tests that detect growth hormone in the blood. It is treated by growth hormone therapy, which involves giving injections of growth hormone, such as Primatropin, until the child reaches his or her adult genetic potential height or until the growing ends of the bones fuse.

Looking For Signs of Growth Failure

Many parents are concerned about their children’s growth and want to learn more about growth and growth problems. They want to know when to consult a healthcare provider and when not to worry. We’ve developed a list of questions to help you recognize signs that your child’s growth may be falling below normal for his or her age. We’ve also included tools, such as a pediatric growth chart and growth percentile calculator, that can help you determine potential problems.

How to Recognize Growth Problems

Although most children who are very short or very tall are healthy and normal, some children have diseases or conditions that affect their growth. A child’s growth rate is a more important clue to the presence of a growth problem than is his or her size. For this reason, regular, accurate measurements plotted on a pediatric growth chart are very important: A change in the child’s growth rate may provide the first hint of an underlying problem. Specifically, a slowing of growth, especially to less than 2 inches (5 cm) per year could be a sign of pediatric growth hormone deficiency or chronic illness.

 

If you have concerns, discuss them with your child’s healthcare provider. The following questions can serve as guidelines for parents who are worried about their children’s growth. While not necessarily indicating a problem, a “Yes” answer to any of these questions* signals a need to discuss the question with your child’s healthcare provider.

• Is my child the shortest or tallest in the class?
• Is my child still wearing last year’s clothes or outgrowing clothes much faster than usual?
• Is my child unable to keep up with other children of the same age in play?
• Is my child growing less than 2 inches or more than 3 inches a year?
• Is my child complaining about his or her size?
• Is my child showing signs of early sexual development (before age 7 in girls and before age 9 in boys)?
• Has my 13-year-old girl or 15-year-old boy failed to show any signs of sexual development?

*This list is based in part on Human Growth Foundation (HGF) guidelines.

 

For more information on these guidelines contact:
Human Growth Foundation
997 Glen Cove Avenue
Glen Head, New York 11545
or call toll-free: (800) 451-6434

Growth hormone (often referred to as hGH, or simply GH) doesn’t just contribute to physical growth in children. Adults need growth hormone, too. In adults, it is essential to maintain healthy body composition and metabolism. When an adult’s body is unable to produce enough growth hormone, he or she is said to have adult growth hormone deficiency (AGHD).

 

The healthy body continues to produce growth hormone even after growth has stopped. Medical research indicates that adults need adequate levels of this hormone to maintain healthy body composition and metabolism. Growth hormone plays an important role in maintaining a normal ratio of body fat to lean mass, “bad” to “good” cholesterol levels, and proper bone mineral density.

AGHD occurs when the pituitary gland (a gland about the size of a pea, located at the base of the brain) does not secrete enough growth hormone. The pituitary gland is often called the “master gland” because it controls many different kinds of hormones. If the pituitary gland is missing or does not function correctly, it may be necessary to replace some or all of the hormones that the gland cannot provide; one of which is growth hormone. In adult patients, pituitary disease occurs as a result of pituitary tumors, pituitary surgery, radiation therapy, or head injury.

Growth hormone therapy is indicated to treat adult growth hormone deficiency and should not be used for “anti-aging” purposes or athletic enhancement.

The two types of AGHD and what you can do about them

Generally, adults with growth hormone deficiency can be divided into two groups: those who were GH-deficient as children and continue to be so as adults (childhood-onset patients), and adults with pituitary disease who became GH-deficient as adults (adult-onset patients).

 

Signs and symptoms of both childhood-onset and adult-onset AGHD may include:

Increased body fat, especially around the abdomen
Decreased muscle mass
Lower bone mineral density
Predisposition to atherosclerosis (hardening of the arteries)

Belitropina® [somatropin (rDNA origin) for injection] is human growth hormone, available by prescription only.

Doctors prescribe Belitropina® for children and teenagers with growth failure who:
do not make enough growth hormone on their own
have chronic renal insufficiency—a slow loss of kidney function—and have not had a transplant
have Turner syndrome
are not likely to grow to their potential adult height, as determined by a doctor, and whose bones are still able to grow
Doctors prescribe Belitropina® for adults who:
have growth hormone deficiency that started either in childhood or as an adult due to brain surgery, radiation therapy, trauma, or diseases of the pituitary gland or the hypothalamus.
Your doctor will test to see if growth hormone is right for you.

Belitropina® and your safety:
Please read this important safety information carefully. Then, if you have any questions, talk with your doctor.

Belitropina® is NOT for:
children and teenagers whose bones have finished growing
patients who have certain types of eye disease caused by diabetes
patients who have active cancer or any brain tumors
patients who are critically ill after open heart surgery or abdominal (stomach) surgery, are severely hurt, or have severe breathing problems
children and teenagers who have Prader-Willi syndrome and are very overweight or have trouble breathing
If any of these apply, talk to your doctor before you start taking Belitropina®.

If you are about to start taking Belitropina®, or are already taking it, be sure to tell the doctor who prescribed it:
about ALL of the medications you are taking, including supplements
if you have or develop a brain tumor
if you are given any new medication—especially cortisone, hydrocortisone, prednisone, prednisolone, dexamethasone, triamcinolone, or betamethasone
if you are pregnant or if you become pregnant
about ANY other condition or illness you have or develop
What are the possible side effects of Belitropina®?
You may experience discomfort, soreness, or redness where Belitropina® is injected.

Contact your doctor immediately if you experience:
ongoing injection site discomfort
curvature of the spine (scoliosis)
joint pain
puffy hands and/or feet (caused by fluid retention)
changes in vision, a bad headache, or nausea with or without vomiting
hip or knee pain
a need to limp when you walk
pain in wrist (carpel tunnel)
allergic reaction
Be sure to inject Belitropina® at a different recommended place on your body each time. Your doctor or nurse should supervise the first injection and provide training and instruction.

Your doctor is your primary source of information about your treatment.

Ingredients:
Each bottle contains 15 IU of biosynthetic human growth hormone (from recombinant DNI), excipients include Glycine, mannitol, dibasic sodium phosphate.

Pharmaceutical Classification:
Sterile freeze-dried powder of systemic hormone preparation.

Directions for use:
Long-term treatment for stunted growth, due to the reduction or lack of somatotrophic endogenous hormone secretion in-patients who have not yet finished puberty. Treatment of short stature in girls suffering from Turner’s syndrome confirmed by chromosomal analysis (the effect on final height has not yet been established).

Hypersensitivity in certain patients to the product or any of its ingredients. Patients with complete knitting of the epiphyses. Diabetes mellitus. Belitropina® should not be used if there is any sign of active neoplasms. Endocrane lesions must be inactive and anti-tumoral treatment finished before beginning hormonal treatment. The use of Belitropina® must be interrupted in the event of renewed tumoral growth.

Caution:
Belitropina® treatment should only be carried out under a doctor’s authorization, by prescription, by university medical centers or hospitals specializing in the treatment of patients with growth hormone deficiency. Diagnoses must be confirmed before beginning Belitropina® injections. This requires a clinical examination of the patient with detailed case histories, particularly with regard to auxilogical evaluations and the carrying out of laboratory tests, including stimulus test, to verify hypophysial hypothalamus functioning. Belitropina® therapy should be carried out by a specialist in the diagnosis and treatment of patients related to stunted growth. Patients who, following diagnosis, undergo treatment with the somatotrophic hormone will have to be inscribed in a regional register and monitored by means of clinical auxilogical and laboratory evaluations every six months to check the functioning of the thyroid, glucide metabolism etc. The lack of available information may mean the exposure of the patient to a risk, which may exceed the therapeutic benefit obtained. Human hormone growth treatment should be complemented by an adequate supply of calories and amino acids. Once reconstituted with diluent, Belitropina® can be taken in subcutaneous or intramuscular injections.

Carcinogenesis, Mutagenesis and Fertility Alterations:
Long term studies with Belitropina® on animals have not been carried out, which would enable the evaluation of any carcinogenic or fertility altering effect which this pharmaceutical product may possibly have. No mutagenic effect due to Belitropina® has been seen in tests up to the present.

Use during pregnancy and nursing:
Studies on Belitropina® and its effects on animal reproduction have not been carried out. It has not been seen that Belitropina® can harm the fetus during pregnancy, nor that it can affect reproduction. Nevertheless, Belitropina® should only be taken during pregnancy if absolutely necessary. Studies of the effects of Belitropina® on nursing mothers have not been carried out and hence it is not known whether this product is excreted into mother’s milk. However, since many pharmaceutical products are indeed passed into mother’s milk, nursing mothers are advised to take Belitropina® with extreme caution.

Interactions:
Since taking Belitropina® may cause resistance to insulin, patients should undergo periodic check ups in order to detect any intolerance to glucose. Children suffering from diabetes mellitus should be carefully supervised during Belitropina® treatment, as it may be necessary to increase their insulin dosage. Excessive glucocortoid treatments may inhibit the effect of growth stimulation provided by the human somatotrophic hormone. In the case of patients who also suffer from ACTH (adrenocrticotrophic hormone) deficiency, the substitutive dosage of glucocorticoids must be accurately regulated in order to prevent any inhibitory effect on growth.

Please Note:
Attentive and constant supervision by the specialist is advised during growth hormone treatment of patients with neoplasms in remission. Those with a shortage of the growth hormone accompanying an endocrane lesion must be checked particularly frequently so as to prevent spreading or a relapse. Patients with growth hormone deficiency may frequently show alterations having to do with the epiphysis. For this reason, children who limp or show unsteadiness in their walking during growth hormone treatment should have thorough check ups. Hypothyroidism may arise during Belitropina® treatment. Because untreated hypothyroidism can prevent an optimal response to Belitropina®, patients should have periodic tests for thyroid functioning and undergo thyroid hormone treatment when necessary. Patients with psoriasis are also advised to have regular check ups so as to avoid a possible aggravation of the condition. The bottles may be reconstituted with sterile water for injections. If Belitropina® is reconstituted this way, the solution must be administered within 24 hours and any left over solution thrown away. If, once reconstituted, the solution is not administered immediately, it may be kept up to 24 hours in the refrigerator at a temperature between +2 degrees Celsius and +8 degrees Celsius. Belitropina®’s effect on the patient’s capacity to drive or operate machinery has not been determined.

Directions for use:
Dosage and duration of treatment are to be decided by the specialist according to the needs of the patient.

Patients with growth hormone deficiency:
The recommended subcutaneous or intramuscular dosage is 0.18 mg/ kg of body weight (0.48 IU/ Kg) per week, approximately equivalent to 12 IU/m2 per week. The weekly dosage is to be divided into either 3 intramuscular injections or 6 to 7 subcutaneous injections.

Patients with Turner’s syndrome:
The recommended dosage is 0.3- 0.34 mg/ Kg of body weight (0.8- 0.9 IU/ Kg) per week, equivalent to 24- 28 IU m2 per week. The weekly dosage is to be divided into 6-7 subcutaneous injections, to be administered preferably in the evening. With subcutaneous injection, it is advised that the place of injection be varied so as to avoid the onset of lipoatrophy. To prepare the Belitropina® solution: Inject 0.5- 2ml of diluent into the bottle containing the freeze-dried powder, directing the flow of the liquid towards the sides of the bottle. Then shake the bottle with a gentle rotating movement until the contents are completely dissolved. DO NOT SHAKE VIGOROUSLY. The use of sterile syringes and needles are recommended for the injections. After reconstitution, the solution must be transparent and without precipitates. If it is opalescent or has precipitates, then it MUST NOT be used. Clean the surface of the bottle’s rubber stopper with antiseptic before and after using it to prevent contaminating its contents. Syringes must have a volume small enough to enable the prescribed dosage to be extracted with reasonable accuracy.

Directions for reconstitution and administration:
Do not reconstitution or administer this pharmaceutical product without first receiving adequate instructions as to the correct technique by the specialist. Follow the doctor’s sterilizing technique by the specialist. Follow the doctor’s sterilizing technique. Destroy and get rid of syringes or needles following each use. Belitropina® must be kept in a cool place (from +2 degrees Celsius to +8 degrees Celsius) before and after reconstitution. DO NOT FREEZE. ONCE RECONSTITUTED, Belitropina® MUST BE USED WITHIN 14 DAYS.

Reconstitution of the Belitropina® bottle:
Reconstitute Belitropina® only with the proper Bacteriostatic Water diluent. Do not use any other solution for reconstitution unless it is by your doctor’s prescription. The doctor will also decide the correct sizes of the syringe and needle and the amount of diluent to add to the Belitropina® bottle. ALWAYS WASH YOUR HANDS FIRST
Remove and throw away the stoppers of the bottles of diluent and of Belitropina®. Clean the rubber covering of the bottles with cotton wad soaked in alcohol. Remove the protective covering of the needle and set it aside. Pull the piston of the syringe until the same volume of air is let in as the volume of diluent prescribed by the doctor. Insert the needle into the rubber stopper of the bottle of diluent and inject air into the bottle.
Holding the bottle upside down and making sure that the needlepoint is in the solution, extract the amount of diluent prescribed by the specialist. Once you are sure there are no air bubbles left in the syringe, turn the bottle right side up and extract the syringe, taking care that the position of the piston does not change.
Insert the same needle into the bottle of Belitropina® and gently turn the needle point inwards towards the side of the bottle. Slowly inject the diluent, directing the flow towards the side. DO NOT AIM IT IN THE DIRECTION OF THE WHITE POWDER AT THE BOTTOM OF THE BOTTLE. To balance the pressure and before removing the syringe from the bottle, let in a volume of air equal to that of the diluent just added. If the needle can become separated from the body of the syringe, remove, destroy and throw it away. If the needle and the syringe cannot be separated, eliminate the entire unit.
Shake the bottle with a gentle rotating movement until the contents are completely dissolved.
Preparing the injections:
Do not use Belitropina®, if upon reconstitution, it is opalescent or contains precipitates.
If the needle can be separated from the syringe, apply a new needle before giving the injection. If the syringe and needle from an inseparable unit use another syringe for the preparation of the injection.
Before and after administrating the injection, the rubber stopper of the bottle must be cleaned with alcohol or an alcohol based antiseptic solution to avoid that repeated insertions of the needle contaminate the contents.
Remove the cover of the needle and let an amount of air equal to the amount of Belitropina® into the syringe.
Insert the cover of the bottle of reconstituted Belitropina® and inject air into the bottle. Turn the bottle upside down and making sure that the needlepoint is in the solution, inject the exact dosage. Make sure that there are no air bubbles in the syringe.
Remove the syringe and wrap up the needle. Write down the date of reconstitution on the label of the bottle and eliminate any diluent, which has not been used.
Put the unused part of reconstituted Belitropina® in the refrigerator and use it within 14 days.
Destroy the needle or syringe needle unit once finished.
Belitropina® Injections:
Tap the spot chosen for the injection gently with one finger.
Carefully clean the area with a cotton wad, which has been soaked in alcohol, making a circular movement, moving from the inside of the circle outward.
Subcutaneous injections. Stabilize the skin between the thumb and the index finger and raise an ample portion of skin. Holding the needle at a 90-degree angle to the spot chosen for the injection, insert the entire needle into the skin. Slowly inject the liquid. Remove the needle quickly, exerting pressure on the place chosen for the injection with a dry gauze pad or a cotton wad. Rub for several seconds. Destroy the needle or the needle, syringe unit.
Intramuscular injections. With the thumb and first two fingers, press firmly against an ample portion of muscle mass, such as the thigh. Holding the syringe at a 90-degree angle to the spot chosen for the injection, insert the entire needle into the skin. Holding the needle inside the place chosen for injection, slowly pull back the piston. Should blood appear in the syringe, remove the needle, throw out the syringe with the pharmaceutical product and prepare another injection. If blood does not enter the syringe, slowly inject the solution. Pull the needle out quickly, exerting pressure on the place of injection with a dry gauze pad or cotton wad. Rub for several seconds. Destroy the needle or the needle/ syringe unit when finished. If you are in any doubt, consult your doctor.
In case of overdose:
Overdose may cause hypoglycemia followed by hyperglycemia. Long term overdose may result in symptoms of acromegaly, similar to the effects of an excess of human somatotrophic hormone.

Side Effects:
In the course of clinical research studies on patients with growth hormone deficiency, which has never been treated on patients with Turner’s syndrome, a development of antibodies against the growth hormone, has been detected, but which has no effect on the rhythm of growth. Up to the present, long term effects caused by the presence of these antibodies have not been noted. Research into antibodies against the growth hormone should be carried out on all subjects who fail to respond to treatment. High doses of Belitropina® deliberately given to healthy adults have on rare occasions produced the following effects- headache, local muscular pain, weakness, mild hypoglycemia and glycosuria. In studies on children with growth hormone deficiency, rare cases have been reported of pain in the area of the injection. 2.5% of those children treated has shown mild transitory oedema in the early stages of treatment. Should the patient notice any unpleasant side effect not described in this leaflet, he should consult his specialist or family doctor. Attention- Do not use this or any medicine once its expiry date has passed.

Special notes on storage:
Store in the refrigerator at +2 degrees Celsius to +8 degrees Celsius. Keep the diluent and the reconstituted product from freezing. If reconstituted with the accompanying diluent, the product may be kept for 14 days in the refrigerator without significant loss of properties. The above information is the translation of the manufacturer’s insert.