Saizen

Name: Saizen

What should i avoid while using somatropin?

If you use Zorbtive to treat short bowel syndrome, avoid drinking fruit juices or soda beverages. Follow the instructions of your doctor or nutrition counselor about what types of liquids you should drink while using Zorbtive.

Avoid drinking alcohol if you have short bowel syndrome. Alcohol can irritate your stomach and could make your condition worse.

Side effects

The following important adverse reactions are also described elsewhere in the labeling:

  • Increased mortality in patients with acute critical illness [see WARNINGS AND PRECAUTIONS]
  • Fatalities in children with Prader-Willi syndrome [see WARNINGS AND PRECAUTIONS]
  • Neoplasms [see WARNINGS AND PRECAUTIONS]
  • Glucose intolerance and diabetes mellitus [see WARNINGS AND PRECAUTIONS]
  • Intracranial hypertension [see WARNINGS AND PRECAUTIONS]
  • Severe hypersensitivity [see WARNINGS AND PRECAUTIONS]
  • Fluid retention [see WARNINGS AND PRECAUTIONS]
  • Hypoadrenalism [see WARNINGS AND PRECAUTIONS]
  • Hypothyroidism [see WARNINGS AND PRECAUTIONS]
  • Slipped capital femoral epiphysis in pediatric patients [see WARNINGS AND PRECAUTIONS]
  • Progression of preexisting scoliosis in pediatric patients [see WARNINGS AND PRECAUTIONS]
  • Lipoatrophy [see WARNINGS AND PRECAUTIONS]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Benzyl alcohol [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

Growth Hormone Deficient Pediatric Patients

In clinical studies in which SAIZEN was administered to growth hormone deficient children, the following reactions were infrequently seen: local reactions at the injection site (such as pain, numbness, redness and swelling), hypothyroidism, hypoglycemia, seizures, exacerbation of preexisting psoriasis and disturbances in fluid balance.

Growth Hormone Deficient Adult Patients

For a description of the clinical trials refer to section 14. During the 6-month placebo-controlled study, adverse reactions were reported in 56 patients (93.3%) in the somatropin-treated group and 42 patients (76.4%) in the placebo-treated group. Adverse reactions with an incidence of ≥ 5% in SAIZEN-treated patients which were more frequent in SAIZEN-treated patients compared with placebo-treated patients are listed in Table 1. Arthralgia, myalgia, peripheral edema, other types of edema, carpal tunnel syndrome, paraesthesia and hypoaesthesia were common in the somatropin-treated patients and reported more frequently than in the placebo group. These types of adverse reactions are thought to be related to the fluid accumulating effects of somatropin. During the placebo-controlled portion of the study, approximately 10% of patients without preexisting diabetes mellitus or impaired glucose tolerance treated with somatropin manifested mild, but persistent, abnormalities of glucose tolerance, compared with none in the placebo group. During the open label phase of the study, approximately 10% of patients treated with somatropin required a small upward adjustment of thyroid hormone replacement therapy for preexisting central hypothyroidism and 1 patient was newly diagnosed with central hypothyroidism. In addition, during the open label phase of the study, when all patients were being treated with somatropin, two patients with preexisting central hypoadrenalism required upward titration of hydrocortisone maintenance therapy which was considered to be suboptimal (unrelated to intercurrent stress, surgery or disease), and 1 patient was diagnosed de novo with central adrenal insufficiency after six months of somatropin treatment. Anti-GH antibodies were not detected.

Table 1 : Adverse Reactions with ≥ 5% Overall Incidence in SAIZEN-Treated Patients Which Were More Frequent in SAIZEN-Treated Patients Compared with Placebo-Treated Patients During a 6 Month Study

Adverse Reaction SAIZEN-Treated
(N=60)
Placebo
(N=55)
Arthralgia 14 (23.3%) 7 (12.7%)
Headache 11 (18.3%) 8 (14.5%)
Edema peripheral 9 (15.0%) 2 (3.7%)
Myalgia 5 (8.3%) 2 (3.6%)
Paraesthesia 4 (6.7%) 1 (1.8%)
Hypoaesthesia 4 (6.7%) 0
Edema dependent 3 (5.0%) 2 (3.6%)
Skeletal Pain 3 (5.0%) 1 (1.8%)
Carpal tunnel syndrome 3 (5.0%) 1 (1.8%)
Edema generalized 3 (5.0%) 0
Chest pain 3 (5.0%) 0
Depression 3 (5.0%) 0
Hypothyroidism 3 (5.0%) 0
Insomnia 3 (5.0%) 0
N = number of patients

The adverse reaction pattern observed during the open label phase of the study was similar to the one presented above.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SAIZEN with the incidence of antibodies to other products may be misleading. In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of SAIZEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products [See WARNINGS AND PRECAUTIONS].

Leukemia has been reported in a small number of growth hormone deficient patients treated with growth hormone. It is uncertain whether this increased risk is related to the pathology of growth hormone deficiency itself, growth hormone therapy, or other associated treatments such as radiation therapy for intracranial tumors. So far, epidemiological data fail to confirm the hypothesis of a relationship between growth hormone therapy and leukemia.

The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and pancreatitis (children and adults) (see WARNINGS AND PRECAUTIONS).

Read the entire FDA prescribing information for Saizen (Somatropin Injection)

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What is the most important information I should know about Saizen (somatropin)?

You should not use somatropin if you have cancer, eye problems caused by diabetes, or if you are being treated for Prader-Willi syndrome and you are overweight or have severe breathing problems. You should not use somatropin if you have a serious illness due to lung failure or complications from recent surgery, injury, or medical trauma.

What happens if I miss a dose?

Use 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 the missed dose.

Call your doctor if you miss more than 3 doses in a row.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause tremors or shaking, cold sweats, increased hunger, headache, drowsiness, weakness, dizziness, fast heartbeat, and nausea. Long-term overdose may cause excessive growth.

What other drugs will affect Saizen (somatropin)?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • birth control pills or hormone replacement therapy

  • insulin or oral diabetes medicine; or

  • steroid medicine (prednisone, dexamethasone, methylprednisolone, and others).

This list is not complete. Other drugs may interact with somatropin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Saizen Dosage and Administration

For subcutaneous injection.

Saizen therapy should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with growth hormone deficiency or adult patients with either childhoodonset or adult-onset growth hormone deficiency.

Pediatric Growth Hormone Deficiency (GHD)

Saizen dosage and administration schedule should be individualized for each patient. The recommended weekly dosage is 0.18 mg/kg of body weight by subcutaneous injection. It should be divided into equal doses given either on 3 alternate days, 6 times per week or daily.

Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human growth hormone.

Treatment with Saizen of growth failure due to growth hormone deficiency should be discontinued when the epiphyses are fused.

Adult Growth Hormone Deficiency (GHD)

Either of two approaches to Saizen dosing may be followed: a weight-based regimen or a non-weight-based regimen.

Weight-based

Based on the dosing utilized in the original pivotal study described herein, the recommended dosage at the start of therapy is not more than 0.005 mg/kg given as a daily subcutaneous injection. The dosage may be increased to not more than 0.01 mg/kg/day after 4 weeks according to individual patient requirements. Clinical response, side effects, and determination of age-and gender-adjusted serum insulin-like growth factor (IGF-1) levels may be used as guidance in dose titration.

Non-weight-based

Alternatively, taking into account more recent literature, a starting dose of approximately 0.2 mg/day (range, 0.15-0.30 mg/day) may be used without consideration of body weight. This dose can be increased gradually every 1 to 2 months by increments of approximately 0.1 to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum IGF-1 concentrations. During therapy, the dose should be decreased if required by the occurrence of adverse reactions and/or serum IGF-1 levels above the age- and gender-specific normal range. Maintenance dosages vary considerably from person to person.

A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger individuals. In addition, obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. In order to reach the defined treatment goal, estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.

Preparation and Administration

Prior to self-administration of the product at home, ensure to train patients and caregivers how to prepare and administer the product correctly to help avoid wrong technique and dosing errors.

Vials

To prevent possible contamination, wipe the rubber vial stopper with an antiseptic solution before puncturing it with the needle. It is recommended that Saizen 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.

After determining the appropriate patient dose, reconstitute each vial of Saizen as follows: 5 mg vial with 1 to 3 mL of Bacteriostatic Water for Injection, USP (Benzyl Alcohol preserved); 8.8 mg vial with 2-3 mL of Bacteriostatic Water for Injection, USP (Benzyl Alcohol preserved). Approximately 10% mechanical loss can be associated with reconstitution and multidose administration.

If sensitivity to the diluent occurs, Saizen may be reconstituted with Sterile Water for Injection, USP. When Saizen is reconstituted in this manner, the reconstituted solution should be used immediately and any unused solution should be discarded [see Warnings and Precautions (5.15)].

To reconstitute Saizen, inject the diluent into the vial of Saizen aiming the liquid against the glass vial wall. Swirl the vial with a GENTLE rotary motion until contents are dissolved completely. DO NOT SHAKE. Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Saizen MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless.

click.easy® cartridges

For drug preparation instructions for Saizen click.easy® cartridges, please refer to the instructions for use provided with click.easy® reconstitution device.

Saizenprep® cartridges

For drug preparation instructions for Saizenprep® cartridges, please refer to the Instructions for Use provided with Saizenprep® reconstitution device.

Injection sites should always be rotated to avoid lipoatrophy.

Contraindications

• Acute Critical Illness

Treatment with pharmacologic amounts of somatropin is contraindicated 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 [see Warnings and Precautions (5.1)].

• Prader-Willi Syndrome in Children

Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment [see Warnings and Precautions (5.2)]. There have been reports of sudden death when somatropin was used in such patients. Saizen is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

• Active Malignancy

In general, somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [See Warnings and Precautions (5.3)].

• Hypersensitivity

Saizen 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 somatropin products [see Warnings and Precautions (5.6)].

• 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.

• Benzyl Alcohol

Saizen reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol [see Warnings and Precautions (5.16)].

Saizen Description

Saizen is a human growth hormone produced by recombinant DNA technology. Saizen has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. Saizen is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene.

Saizen is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The reconstituted solution has a pH of 6.5 to 8.5.

Vials

Saizen is available in 5 mg and 8.8 mg vials. The quantitative composition per vial is:

5 mg vial:

Each vial contains 5.0 mg somatropin, 34.2 mg sucrose and 1.16 mg O-phosphoric acid. The pH is adjusted with sodium hydroxide or O-phosphoric acid.

8.8 mg vial:

Each vial contains 8.8 mg somatropin, 60.2 mg sucrose and 2.05 mg O-phosphoric acid. The pH is adjusted with sodium hydroxide or O-phosphoric acid.

Diluent

The diluent is Bacteriostatic Water for Injection, USP containing 0.9% Benzyl Alcohol added as an antimicrobial preservative.

Reconstitution devices:

click.easy® reconstitution device

Saizen 8.8 mg vial contained in the click.easy® reconstitution device.

Each vial contains 8.8 mg somatropin, 60.2 mg sucrose and 2.05 mg O-phosphoric acid. The pH is adjusted with sodium hydroxide or O-phosphoric acid.

Diluent

The diluent contained in click.easy® device is 0.3% (w/v) metacresol in Sterile Water for Injection added as an antimicrobial preservative. The reconstituted solution has a pH of 6.5 to 8.5.

Saizenprep® reconstitution device

Saizen 8.8 mg vial supplied with the Saizenprep® reconstitution device. Each vial contains 8.8 mg somatropin, 60.2 mg sucrose and 2.05 mg O-phosphoric acid. The pH is adjusted with sodium hydroxide or O-phosphoric acid.

Diluent

The diluent supplied with Saizenprep® reconstitution device is 0.3% (w/v) metacresol in Sterile Water for Injection added as an antimicrobial preservative. The reconstituted solution has a pH of 6.5 to 8.5.

click.easy® Reconstitution Device Saizen® (somatropin) for injection, for subcutaneous use 8.8 mg INSTRUCTIONS FOR USE

For complete dosing and safety information, please refer to the Saizen Package Insert.

COMPOSITION

Each vial of Saizen 8.8 mg contained in the 5.83 mg/mL click.easy® device contains the following ingredients:

  • Active substance: Somatropin (Recombinant Human Growth Hormone) 8.8 mg.
  • Excipients: Sucrose, Phosphoric acid, Sodium Hydroxide; 1 mL of the reconstituted Saizen solution contains 5.83 mg of somatropin when reconstituted with the contents of the diluent cartridge.

COMPOSITION OF DILUENT

Each cartridge of diluent contained in the click.easy® reconstitution device contains the following ingredients:

5.83 mg/mL click.easy®

Active substance: Metacresol USP (4.52 mg),

Excipients: Phosphoric acid 85% to adjust pH, Water for Injection, USP (1.51 mL)

Patients with a known sensitivity to any of the above active substances or excipients should avoid using this product.

PHARMACEUTICAL FORM

Powder and diluent for solution for injection: Powder and diluent (0.3% (w/v) metacresol in water for injection) for parenteral use.

METHOD AND ROUTE OF ADMINISTRATION

The product (powder in vials) must be reconstituted with the enclosed diluent (0.3% (w/v) metacresol in water for injection) using the click.easy® reconstitution device.

The reconstituted solution is intended for subcutaneous administration (under the skin) and should be clear with no particles. If the solution contains particles, it must not be injected.

IMPORTANT INFORMATION

Patients should be thoroughly instructed in the reconstitution procedure.

For young children, the reconstitution process should be supervised by an adult.

For administration of Saizen 8.8 mg contained in the click.easy® device, please read the following instructions carefully. Please consult your doctor, nurse or pharmacist if you have any questions concerning the reconstitution process.

Check that the click.easy® reconstitution device contains an unused Saizen vial (a) and an unused diluent cartridge (c).

Do NOT use the device if the vial or cartridge appear empty or used and return it to your pharmacist or doctor.

Wash your hands with soap and water.

HOW TO PREPARE YOUR SOLUTION OF Saizen®

  1. Place the click.easy® device vertically on a clean flat surface with the Saizen vial on the bottom and the diluent cartridge outer housing cap (g) on top facing upward.
  2. Push on the top diluent cartridge outer housing cap (g) firmly until the Saizen vial outer housing (h) is completely inside the main body. This step breaks the tamper evident seal on the vial.
  3. Turn the diluent cartridge outer housing cap (g) clockwise until the green square (f) is visible at the lower end of the narrow rectangular opening. Push the diluent cartridge outer housing cap down very slowly until it will go no further and the green colored square appears at the upper end of the narrow rectangular opening.
  4. Check that all the diluent has been transferred into the vial. Dissolve the Saizen powder with the diluent by gently swirling the click.easy® device (Note: Do not transfer the diluent forcefully or shake the click.easy® device. A fast transfer of the diluent or shaking of the click.easy® device will create more foam). Let the solution stand for 2-5 minutes until the Saizen powder is completely dissolved.
  5. Turn the click.easy® device upside down so the Saizen vial is now on top and pull the diluent cartridge outer housing cap slowly downwards until the solution is completely drawn back into the cartridge. Check that no more than one or two drops of solution remain in the vial.
  6. If there are more than one or two drops of solution remaining in the vial, slowly push the diluent cartridge outer housing cap up until some of the solution is back in the vial and gently tap the click.easy® device. Then draw the solution slowly again back into the cartridge.
  7. Remove any excess air that has been drawn into the cartridge by slowly pushing the cap up until no air bubble is visible in the cartridge. There should be no air bubble in the cartridge (Note: Avoid pulling the cap down too fast, as this will draw air into the cartridge).
  8. Turn the click.easy® device so that the cap is again on the top. Unscrew the cap and remove it.
  9. Remove the cartridge containing the reconstituted Saizen solution from the click.easy® device by grasping the end of the cartridge and pulling straight out of the outer housing.
  10. Carefully peel off the outer white label on the cartridge using the tab provided by slowly pulling in the direction of the black arrow.
  11. Write the reconstitution date on the transparent inner label on the cartridge. This cartridge now contains the reconstituted Saizen solution that will be used for your treatment.
  12. The cartridge containing the reconstituted Saizen solution is now ready to be used (Note: Please read the instruction manual provided with the injection device for instruction on how to inject the reconstituted Saizen solution from the cartridge).
  13. The Saizen reconstituted solution should be stored in a refrigerator (2°-8°C / 36°-46°F) and should be used within 21 days after reconstitution. Do not freeze.
  14. Discard the click.easy® device containing the empty Saizen vial safely in accordance with your local requirements. It is not necessary to remove the empty Saizen vial from the click.easy® device prior to disposal.
  15. Injections should be given in different parts of your body. Do not use any areas in which you feel lumps, firm knots, depressions, or pain; talk to your doctor or healthcare professional about anything you find. Clean the skin at the injection site with soap and water.

STABILITY AND STORAGE

Vials of Saizen 8.8 mg pre-assembled in the click.easy® reconstitution device should be stored in the original package at room temperature (15°-30°C / 59°-86°F).

Saizen 8.8 mg reconstituted solution should be stored in a refrigerator (2°-8°C / 36°-46°F) and should be used within 21 days after reconstitution.

Do not freeze.

HOW SUPPLIED

Saizen 8.8 mg contained in the click.easy® device is available in the following pack sizes:

1 vial of Saizen 8.8 mg product and 1 cartridge of 1.51 mL diluent pre-assembled in 1 reconstitution device (click.easy®) comprising 1 device housing and 1 sterile transfer cannula
NDC 44087-1080-1

Manufactured for:
EMD Serono Inc., Rockland, MA 02370

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