Manufacturer Information

The following information is the translation of the manufacturer's insert. It is provided under the supplying company's terms and conditions and should not replace the advice of your personal physician.

SAIZEN® 1.33mg

The ampoule bottle with lyophilised powder contains:
Somatropin .........1.33 mg
equivalent to ......... 4 IU
Excipient ......... s.q.
The small ampoule of diluting agent contains: 0.9% sodium chloride solution .........1 ml

Properties:

The main active ingredient of Saizen® is Somatropin, a biosynthetic human growth hormone produced from mammal cells through genetic engineering. It contains 191 amino acids, in identical sequence to that of the natural hypophysiary hormone. Saizen® brings about an increase in the average growth rate by means of Somamedins or growth factors similar to insulin.

Contraindications:

Individual hypersensitivity to the active component in the product. Diabetes mellitus must be considered as a relative contraindication. In subjects suffering from diabetes mellitus, treatment should be carried out under strict medical and laboratory supervision. Saizen® must not be used when there are progression data of a concomitant cerebral tumour.

Adverse side effects

Pharmacokinetic and toxicological studies carried out with Saizen® and pit-hGH have confirmed that the safety of the recombinant product is similar to that of the natural growth hormone, with no side effects produced by the drug itself. However, treatment with human proteins can cause reactions as a result of hypersensitivity (such as redness and itchiness in the area of the injection site), the formation of antibodies with or without the attenuating effect of growth, or both.

In a small number of patients, where short stature is due to a genetic defect (depletion of the gene complex for hGH), Somatropin treatment can stimulate the production of antibodies which attenuate growth in the majority of cases.

Precautions:

Treatment must be carried out under strict periodic medical supervision. Patients with a deficiency of the growth hormone secondary to an intracraneal lesion should be examined frequently in order to follow the progression or recurrence of the underlying pathological process. Administering Saizen® subcutaneously in the same site over a prolonged period of time may cause lipoatrophy. This can be prevented if the injection site is changed each time.

Drug interactions:

Concomitant therapy with corticoids may inhibit the growth promoting effect of Somatropin.

Directions for use:

Saizen® can be administered intramuscularly or subcutaneously, preferably at bedtime. The contents of one ampoule bottle must be reconstituted with the diluting agent, by inserting the liquid into the ampoule bottle and gently shaking it until it is completely dissolved. Do not shake it vigorously, as this can cause a slight darkening of the solution.

Administration method:

Saizen® can be administered intramuscularly or subcutaneously, preferably at bedtime. The dosage and method for administering Saizen® must be adapted to the needs of each patient.

Dosage: Follow your doctor's instructions

Store in the refrigerator at 2ºC to 8ºC. Do not freeze.
Do not use if the seal has been broken.
Do not use after the expiry date.
Once the mixture has been made, the product can be stored in the refrigerator at 2ºC - 8ºC.

Presentation:

Box with 1 ampoule bottle with lyophilised powder, 1.33 mg equivalent to 4 IU, and 1 small ampoule with 1 ml of diluting agent.

Keep out of children's reach.

Do not use if you are pregnant or breast-feeding.

Sold by medical prescription only.

Ingredients:
Each bottle contains 4 IU of biosynthetic human growth hormone (from recombinant DNI), excipients include Glycine, mannitol, bibasic sodium phosphate. Each bottle of diluent contains m-cresol, glycerin and water for injections.
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).
Contraindications:
Hypersensitivity in certain patients to the product or any of its ingredients. Patients with complete knitting of the epiphyses. Diabetes mellitus. Humatrope 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 Humatrope must be interrupted in the event of renewed tumoral growth. Humatrope must not be reconstituted with the accompanying diluent if the patient is sensitive to m-cresol or glycerin.
Caution:
Humatrope 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 Humatrope 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. Humatrope 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 the accompanying diluent, Humatrope can be taken in subcutaneous or intramuscular injections.
Carcinogenesis, Mutagenesis and Fertility Alterations:
Long term studies with Humatrope 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 Humatrope has been seen in tests up to the present.
Use during pregnancy and nursing:
Studies on Humatrope and its effects on animal reproduction have not been carried out. It has not been seen that Humatrope can harm the fetus during pregnancy, nor that it can affect reproduction. Nevertheless, Humatrope should only be taken during pregnancy if absolutely necessary. Studies of the effects of Humatrope 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 Humatrope with extreme caution.
Interactions:
Since taking Humatrope 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 Humatrope 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 Humatrope treatment. Because untreated hypothyroidism can prevent an optimal response to Humatrope, 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. In the event of sensitivity to the accompanying diluent, the bottles may be reconstituted with sterile water for injections. If Humatrope 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. Humatrope’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 Humatrope solution: Inject 0.5- 2ml of the 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. Humatrope must be kept in a cool place (from +2 degrees Celsius to +8 degrees Celsius) before and after reconstitution. DO NOT FREEZE. ONCE RECONSTITUTED, HUMATROPE MUST BE USED WITHIN 14 DAYS.
Reconstitution of the Humatrope bottle:
Reconstitute Humatrope only with Humatrope 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 Humatrope bottle. ALWAYS WASH YOUR HANDS FIRST
 

1. Remove and throw away the stoppers of the bottles of diluent and of Humatrope. Clean the rubber covering of the bottles with cotton wad soaked in alcohol (see figure 1 in pack). 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.
    
2. Holding the bottle upside down and making sure that the needlepoint is in the solution, extract the amount of diluent prescribed by the specialist (see figure 2 in pack). 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.
    
3. Insert the same needle into the bottle of Humatrope and gently turn the needle point inwards towards the side of the bottle. Slowly inject the diluent, directing the flow towards the side (see figure 3 in pack). 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.
    
4. Shake the bottle with a gentle rotating movement until the contents are completely dissolved (see figure 4 in pack).
    

Preparing the injections:

1. Do not use Humatrope, if upon reconstitution, it is opalescent or contains precipitates.
    
2. 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.
    
3. 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.
    
4. Remove the cover of the needle and let an amount of air equal to the amount of Humatrope into the syringe.
    
5. Insert the cover of the bottle of reconstituted Humatrope 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 (see figure 2 in pack). Make sure that there are no air bubbles in the syringe.
    
6. 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.
    
7. Put the unused part of reconstituted Humatrope in the refrigerator and use it within 14 days.
    
8. Destroy the needle or syringe needle unit once finished.
    

Humatrope Injections:
 

1. Tap the spot chosen for the injection gently with one finger.
    
2. 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.
    
3. 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.
    
4. 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 Humatrope 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.

Overview