Consumer medicine information

Omnitrope

Somatropin

BRAND INFORMATION

Brand name

Omnitrope

Active ingredient

Somatropin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omnitrope.

What is in this leaflet

This leaflet answers some common questions about Omnitrope.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you or your child.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Omnitrope is used for

This medicine is used to treat:

  • short stature in children due to growth hormone deficiency
  • girls with growth disturbance associated with Turner syndrome
  • growth disturbance in children with chronic renal insufficiency.

It contains the active ingredient somatropin. Somatropin is a biosynthetic human growth hormone which is a protein molecule occurring naturally in humans. Omnitrope is identical to the body's own growth hormone.

Ask your doctor if you have any questions about why this medicine has been prescribed for you or your child. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you use Omnitrope

When you must not use it

Do not use this medicine if you have an allergy to:

  • somatropin, the active ingredient
  • any of the other ingredients listed at the end of this leaflet under Product description.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use this medicine if you have any of the following medical conditions:

  • active tumours or evidence of tumour growth
  • serious injury or illness, or surgical procedures, requiring intensive care
  • closed epiphyses if you are a child (this means that the growth area of the bones is unable to grow anymore)
  • are currently being treated for cancer
  • have Prader-Willi syndrome and are severely overweight or have marked difficulty breathing
  • Do not give this medicine to a child under the age of 3 years.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you or your child should start using this medicine, talk to your doctor.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • diabetes mellitus
  • thyroid disease
  • cancer
  • any disorder relating to hormones including adrenocortical insufficiency (also known as ACTH deficiency)
  • kidney transplant.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start using Omnitrope.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

In particular, tell your doctor if you are taking:

  • any medicine for the treatment of diabetes
  • corticosteroids such as cortisol or dexamethasone eg. For the treatment of severe asthma, some skin conditions or rheumatoid arthritis
  • some epilepsy medicines, e.g. carbamazepine, ethosuximide or tiagabine
  • medicines used to treat diabetes
  • thyroxine (thyroid hormone) for the treatment of thyroid deficiency
  • replacement therapy for Adrenocorticotropic hormone (ACTH) deficiency, such as hydrocortisone or fludrocortisone
  • ciclosporin e.g. for the treatment of severe skin disease (psoriasis), rheumatoid arthritis or after transplant surgery
  • hormone therapy e.g. HRT for oestrogen deficiency, menopause or osteoporosis (bone thinning), testosterone for hormone deficiency in men, or other hormone therapy for contraception ("the Pill"), endometriosis or some cancers.

These medicines may be affected by Omnitrope or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How to use Omnitrope

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to use

The dose of Omnitrope is different for each person. Your doctor will tell you what the right dose for you or your child is.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to use.

Follow the instructions they give you. If you use the wrong dose, Omnitrope may not work as well and your problem may not improve.

How to use it

After taking Omnitrope out of the refrigerator allow glass cartridge to reach room temperature (about 30 mins) prior to injection.

Omnitrope 5 mg/1.5 mL, 10 mg/1.5 mL and 15 mg/1.5 mL Solution for Injection

Reconstitution is not required for Omnitrope Solution for Injection. This medicine is ready-to-use.

Put the glass cartridge containing the Omnitrope solution in the injector pen. Use

  • Sure Pal 5 for Omnitrope 5 mg/1.5 mL Solution for Injection for SurePal 5
  • Omnitrope Pen 10 for Omnitrope 10 mg/1.5 mL Solution for Injection
  • Sure Pal 10 for Omnitrope 10 mg/1.5 mL Solution for Injection for SurePal 10 and
  • SurePal 15 for Omnitrope 15 mg/1.5 mL Solution for Injection for SurePal 15

Follow the instructions that come with the pen.

When to use Omnitrope

Omnitrope is usually injected once a day in the evening.

How long to use Omnitrope

Continue using your medicine for as long as your doctor tells you. Your doctor will determine when your treatment should be stopped.

If you forget to use it

Inject your dose as soon as you remember, and continue to inject it as you would normally.

If it is almost time for your next dose, skip the dose you missed and inject your next dose when you are meant to.

Do not inject a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have used too much Omnitrope. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using Omnitrope

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Omnitrope.

Tell any other doctors, dentists, and pharmacists who treat you that you are using this medicine.

If you become pregnant while using this medicine, tell your doctor immediately.

Tell your doctor if you start to have difficulty breathing or start to snore, or have an increase in snoring while you are using Omnitrope.

Tell your doctor if you stop or change your oral oestrogen therapy.

Tell your doctor if you stop or change your glucocorticoid therapy.

Keep all of your doctor's appointments so that your progress can be checked.

Change the site of injection every day.

Inspect the product carefully before use. Only use the injection if the solution is clear. If the solution is cloudy or contains particles, the contents must not be injected.

Things you must not do

Do not use Omnitrope to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you. Also do not let anyone use your injector pen.

Do not stop using your medicine or change the dosage without checking with your doctor.

Things to be careful of

Because growth hormone may interfere with your body's use of insulin, you will have to be watchful of glucose intolerance during therapy. Symptoms of glucose intolerance include increased thirst and need to pass urine.

Follow the instructions for administration of Omnitrope carefully. Not following the instructions might decrease the activity of your medicine or lead to a broken pen injector or cartridge.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Omnitrope.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • reactions at the injection site, such as bruising, pain, numbness, redness or swelling
  • swelling of arms or legs
  • joint and/or muscle pain
  • stiffness of the hands and feet
  • tingling or numbness in your fingers, hands or feet.

These are mild side effects of the medicine that usually only occur at the beginning of therapy but are also dependent on dose.

Tell your doctor as soon as possible if you notice any of the following:

  • recurrent headache, blurred vision, nausea and/or vomiting
  • swelling of the face
  • increased thirst and need to pass urine, particularly if you are overweight or if anyone in your family has diabetes
  • extreme tiredness, lethargy, muscle weakness or change to appetite
  • curvature of the spine
  • limping or pain in the hip and knee.

The above list includes serious side effects. You or your child may need urgent medical attention or hospitalisation. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

After using Omnitrope

Storage

Keep your medicine in the original container. If you take it out of its original container it may not keep well.

Keep your medicine in the refrigerator at 2-8°C. Do not freeze.

Keep it where children cannot reach it.

Use an insulated container for transporting your medicine if you are travelling.

Omnitrope 5 mg/1.5 mL, 10 mg/1.5 mL Solution for Injection and 15 mg/1.5 mL Solution for Injection

Remove the needle from the injector pen after each injection. Return the injector pen with the cartridge to the refrigerator after each use.

If you are using Omnitrope 5 mg/1.5 mL for SurePal 5 discard the cartridge 21 days after injecting the first dose.

If you are using Omnitrope 10 mg/1.5 mL / Omnitrope 10 mg/1.5 mL for SurePal 10 discard the cartridge 28 days after injecting the first dose.

If you are using Omnitrope 15 mg/1.5 mL discard the cartridge 28 days after injecting the first dose.

Disposal

Used needles and the empty cartridges or vials should be disposed of in a sharps container or a container of hard plastic or glass.

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Omnitrope Solution for Injection is a clear and colourless solution.

Package quantities

Omnitrope 5 mg/1.5 mL, 10 mg/1.5 mL & 15 mg/1.5 mL Solution for Injection - Each pack contains 1, 5 or 10 colourless glass cartridges.

Ingredients

Active ingredients:

  • Omnitrope 10 mg/1.5 mL Solution for Injection - 6.67 mg/mL somatropin (rbe)
  • Omnitrope 5 mg/1.5 mL for SurePal 5 - 3.33 mg/mL somatropin (rbe)
  • Omnitrope 10 mg/1.5 mL for SurePal 10 - 6.67 mg/mL somatropin (rbe)
  • Omnitrope 15 mg/1.5 mL for SurePal 15 - 10 mg/mL somatropin (rbe)

Inactive ingredients:

Omnitrope 5 mg/1.5 mL for SurePal 5:

  • monobasic sodium phosphate
  • dibasic sodium phosphate heptahydrate
  • poloxamer
  • mannitol
  • benzyl alcohol
  • phosphoric acid
  • sodium hydroxide
  • water for injection.

Omnitrope 10 mg/1.5 mL / Omnitrope 10 mg/1.5 mL for Sure Pal 10:

  • monobasic sodium phosphate
  • dibasic sodium phosphate heptahydrate
  • poloxamer
  • phenol
  • glycine
  • phosphoric acid
  • sodium hydroxide
  • water for injections.

Solvent - Water for Injections:

  • water for injections.

Solvent - Benzyl alcohol 1.5%:

  • benzyl alcohol
  • water for injections.

Omnitrope 15 mg/1.5 mL for Sure Pal 15:

  • monobasic sodium phosphate
  • dibasic sodium phosphate heptahydrate
  • poloxamer
  • phenol
  • sodium chloride
  • phosphoric acid
  • sodium hydroxide
  • water for injections

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

This leaflet was revised in June 2020.

Australian Register Numbers:

Omnitrope 5 mg/1.5 mL Solution for Injection for SurePal 5- AUST R 224622

Omnitrope 10 mg/1.5 mL Solution for Injection - AUST R 162522

Omnitrope 10 mg/1.5 mL Solution for Injection for SurePal 10 - AUST R 224623

Omnitrope 15 mg/1.5 mL Solution for Injection for SurePal 15 - AUST R 205625

Published by MIMS July 2020

BRAND INFORMATION

Brand name

Omnitrope

Active ingredient

Somatropin

Schedule

S4

 

1 Name of Medicine

Somatropin (rbe) (recombinant human growth hormone, r-hGH).

2 Qualitative and Quantitative Composition

Omnitrope 5 mg/1.5 mL solution for injection contains 3.33 mg/mL somatropin.
Omnitrope 5 mg/1.5 mL solution for injection for SurePal 5 contains 3.33 mg/mL somatropin.
Omnitrope 10 mg/1.5 mL solution for injection contains 6.67 mg/mL somatropin (rbe).
Omnitrope 10 mg/1.5 mL solution for injection for SurePal 10 contains 6.67 mg/mL somatropin (rbe).
Omnitrope 15 mg/1.5 mL solution for injection for SurePal 15 contains 10 mg/mL somatropin (rbe).
Omnitrope 1.33 mg powder for injection contains 1.33 mg/mL somatropin (rbe) on reconstitution.
Omnitrope 5 mg powder for injection contains 5 mg/mL somatropin (rbe) on reconstitution.

List of excipients with known effect.

Mannitol (Omnitrope 5 mg/1.5 mL solution for injection preparations).
Omnitrope is produced using recombinant DNA technology. The active substance somatropin (biosynthetic human growth hormone, rDNA-derived human growth hormone [r-hGH]) is produced in cell culture by Escherichia coli cells bearing the gene for human growth hormone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Omnitrope solution for injection is a clear, colourless solution.
Omnitrope powder for injection is a white to off-white powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Omnitrope is intended for the long-term treatment of children (above three years of age) with:
growth disturbance due to insufficient secretion of pituitary growth hormone;
growth disturbance associated with gonadal dysgenesis (Turner syndrome);
growth disturbance associated with chronic renal insufficiency.

4.2 Dose and Method of Administration

Dosage.

Therapy with somatropin should be initiated and monitored by physicians who are experienced in the diagnosis and management of patients with growth hormone deficiency.
The dose is based on bodyweight and must always be adjusted individually in accordance with the response to therapy.
Daily administration by subcutaneous injection in the evening is recommended. The injection sites have to be rotated to minimise the risk of local lipoatrophy.
Patients and caregivers have to receive appropriate training and instruction on the proper use of the Omnitrope vials, the cartridges with solvent, the transfer set and the pen from their physician or other suitably qualified health professionals.

Growth disturbance due to insufficient secretion of growth hormone in children.

Generally, a dose of 0.025 to 0.035 mg/kg bodyweight per day or 0.7 to 1.0 mg/m2 body surface area per day is recommended. If the response to therapy is not satisfactory in the following years, the dose can be increased, as higher doses have been used.

Growth disturbance in girls due to Turner syndrome.

A dose of 0.045 to 0.05 mg/kg bodyweight per day or 1.4 mg/m2 body surface area per day is recommended. If the response to therapy is not satisfactory in the following years, the dose can be increased.

Growth disturbance in chronic renal insufficiency.

A dose of 0.045 to 0.05 mg/kg bodyweight per day or 1.4 mg/m2 body surface area per day is recommended. A dosage adjustment may be necessary after 6 months. If the response to therapy is not satisfactory, the dose can be increased.

Duration of treatment.

There is no specific time limit for the duration of treatment with somatropin. Treatment is to be discontinued when the patient has reached a satisfactory final height, when the epiphyses are closed or when the patient no longer responds to growth hormone therapy. Response to somatropin therapy in paediatric patients tends to decrease with time. However, failure to increase growth velocity, particularly during the first year of treatment, suggests the need for close assessment of compliance and other causes of growth failure such as hypothyroidism, undernutrition and advanced bone age.

Method of administration.

Reconstitution and stability of solution.

As with all parenteral drug products, the solution should be clear after reconstitution and storage. If the solution is cloudy, the contents must not be injected.

Omnitrope 5 mg/1.5 mL solution for injection.

Omnitrope 5 mg/1.5 mL is a ready to use solution, which is filled in glass cartridges. This presentation is intended for multiple use with a pen device. The Omnitrope Pen 5 needs to be used to administer Omnitrope 5 mg/1.5 mL. After the first injection, the contents of the cartridge must be used within 21 days and the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator). For microbiological reasons, any remaining solution should be discarded after 21 days.
The Omnitrope Pen 5 is intended for use by a single patient only.

Omnitrope 5 mg/1.5 mL solution for injection for SurePal 5.

Omnitrope 5 mg/1.5 mL is a ready to use solution, which is filled in glass cartridges. This presentation is intended for multiple use with a pen device (SurePal). SurePal 5 needs to be used to administer Omnitrope 5 mg/1.5 mL. The cartridges for SurePal 5 are irreversibly integrated in a transparent container called cartridge holder, which serves as an adaptor for SurePal 5. After the first injection, the contents of the cartridge must be used within 21 days and the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator). For microbiological reasons, any remaining solution should be discarded after 21 days.
SurePal 5 is intended for use by a single patient only.

Omnitrope 10 mg/1.5 mL solution for injection.

Omnitrope 10 mg/1.5 mL is a ready to use solution, which is filled in glass cartridges. This presentation is intended for multiple use with a pen device. The Omnitrope Pen 10 needs to be used to administer Omnitrope 10 mg/1.5 mL. After the first injection, the contents of the cartridge must be used within 28 days and the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator). For microbiological reasons, any remaining solution should be discarded after 28 days.
The Omnitrope Pen 10 is intended for use by a single patient only.

Omnitrope 10 mg/1.5 mL solution for injection for SurePal 10.

Omnitrope 10 mg/1.5 mL is a ready to use solution, which is filled in glass cartridges. This presentation is intended for multiple use with a pen device (SurePal). SurePal 10 needs to be used to administer Omnitrope 10 mg/1.5 mL. The cartridges for SurePal 10 are irreversibly integrated in a transparent container called cartridge holder, which serves as an adaptor for SurePal 10. After the first injection, the contents of the cartridge must be used within 28 days and the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator). For microbiological reasons, any remaining solution should be discarded after 28 days.
SurePal 10 is intended for use by a single patient only.

Omnitrope 15 mg/1.5 mL solution for injection for SurePal 15.

Omnitrope 15 mg/1.5 mL is a ready to use solution, which is filled in glass cartridges. This presentation is intended for multiple use with a pen device (SurePal). SurePal 15 needs to be used to administer Omnitrope 15 mg/1.5 mL. The cartridges for SurePal 15 are irreversibly integrated in a transparent container called cartridge holder, which serves as an adaptor for SurePal 15. After the first injection, the contents of the cartridge must be used within 28 days and the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator). For microbiological reasons, any remaining solution should be discarded after 28 days.
SurePal 15 is intended for use by a single patient only.

Omnitrope 1.33 mg/mL powder for injection*.

Omnitrope 1.33 mg/mL is supplied in a vial containing the active substance as a powder and the solvent filled in a vial for single use. Each vial must be reconstituted with the accompanying water for injection.
The reconstituted solution is clear and colourless. As the reconstituted solution contains no preservative, use once only and discard any residue. If storage is necessary, the reconstituted solution should be stored at 2°C to 8°C for not more than 24 hours.
The product is for single use in one patient only.

Omnitrope 5 mg/mL powder for injection*.

Omnitrope 5 mg/mL is supplied in a vial containing the active substance as a powder and a cartridge containing the solvent. It should be reconstituted with a transfer set as recommended in the information provided with the transfer set. Reconstitute the Omnitrope vial only with the accompanying solvent for parenteral use. Use the complete contents of the cartridge. This presentation is intended for multiple use with a pen device.
After reconstitution, the content of the cartridge is stable for at least 21 days when stored at 2°C to 8°C. The reconstituted solution is clear and colourless. For microbiological reasons, any remaining solution should be discarded after 21 days.
After reconstitution and first injection, the cartridge should remain in the pen and has to be kept at 2°C to 8°C (in a refrigerator).
The pen is intended for use by a single patient only.
*Product is not marketed.

4.3 Contraindications

Treatment with Omnitrope is contraindicated:
in patients with evidence of malignancies. Intracranial lesions have to be inactive and antitumour therapy has to be completed prior to treatment. Treatment with Omnitrope should be discontinued if there is any evidence of recurrent tumour activity;
for growth promotion in paediatric patients with closed epiphyses;
in patients with known hypersensitivity to somatropin or to any of the excipients;
in patients with acute critical illness due to complications following open heart surgery or abdominal surgery, multiple accident trauma, extensive burns or to patients having acute respiratory failure (see Section 4.4 Special Warnings and Precautions for Use).
in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see Section 4.4 Special Warnings and Precautions for Use).
in newborns, Omnitrope 5 mg/1.5 mL solution for injection/Omnitrope 5 mg/1.5 mL solution for injection for SurePal 5 and Omnitrope 5 mg/mL powder for injection* (after reconstitution with the solvent) should not be used because of the presence of the preservative, benzyl alcohol.
*Not marketed.

4.4 Special Warnings and Precautions for Use

Therapy with Omnitrope should be initiated and monitored by physicians who are appropriately qualified and experienced in the diagnosis and management of patients with growth hormone deficiency. The maximum recommended daily dose should not be exceeded (see Section 4.2 Dose and Method of Administration).
There have been reports of fatalities associated with the use of growth hormone in paediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of respiratory impairment or sleep apnoea, or unidentified respiratory infection. Another possible risk factor may be male gender. (Omnitrope is not indicated for use in patients with Prader-Willi syndrome.)

Metabolism.

Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore, patients should be observed for evidence of glucose intolerance during Omnitrope treatment. In rare cases, the diagnostic criteria for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such as obesity, family history, steroid treatment or pre-existing impaired glucose tolerance have been present in most cases where this occurred. Omnitrope should be used with caution in patients with diabetes mellitus or a family history of diabetes mellitus. In patients with already manifested diabetes mellitus, the antidiabetic therapy might require adjustment when somatropin is instituted.

Endocrine system.

Hypothyroidism may develop during therapy with somatropin, and inadequate treatment of hypothyroidism may prevent optimal response to treatment with Omnitrope. Therefore, thyroid hormone levels must be checked periodically during Omnitrope therapy and patients should be treated with thyroid hormone, when indicated.
During treatment with somatropin, an enhanced T4 to T3 conversion has been found, which may result in a reduction in serum T4 concentrations and an increase in serum T3 concentrations. In general, the peripheral thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving replacement therapy with thyroxin, mild hyperthyroidism may occur. It is therefore advisable to test thyroid function after starting treatment with somatropin and after dose adjustment.
Large doses of glucocorticoids may inhibit the growth promoting effect of growth hormone. Patients with coexisting corticotropin deficiencies should have their glucocorticoid replacement doses carefully adjusted.
Somatropin has been reported to reduce serum cortisol levels. Changes to serum levels of unbound serum cortisol have not been reported. The clinical relevance of these findings seems limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.
To achieve a satisfactory stimulation of growth, some girls with Turner syndrome may require a higher dose during the first year of treatment.
Patients with pan hypopituitarism are at risk of adrenal insufficiency after treatment with growth hormone is commenced, particularly if this has not previously been recognised or the patients are on inadequate replacement. Standard replacement therapy should be closely monitored in patients with (pan)hypopituitarism.
Patients with chronic renal disease may develop hyperparathyroidism which should be treated appropriately before initiation of somatropin therapy.
Introduction of somatropin treatment may result in inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and reduced serum cortisol concentrations. In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required. In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses, following initiation of somatropin treatment (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Nervous system.

In cases of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for papilloedema is recommended as some rare cases of benign intracranial hypertension have been reported during somatropin treatment. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension has to be considered and, if appropriate, Omnitrope treatment should be interrupted. At present, insufficient experience exists on how to restart treatment in patients after normalisation of intracranial pressure. If restarting treatment is considered appropriate, the patient has to be carefully monitored for the absence of symptoms of increased intracranial pressure.

Musculoskeletal system.

Progression of scoliosis can occur in patients who experience rapid growth. Physicians should be alert to this abnormality, which may become apparent during growth hormone therapy due to the rapid increase in growth rate. Signs of scoliosis should be monitored during treatment.
Patients with endocrine disorders, including growth hormone deficiency, hypopituitarism and renal osteodystrophy, may have an increased incidence of slipped capital femoral epiphyses. Any child who develops a limp or complains of hip or knee pain during Omnitrope treatment should be evaluated as this may indicate development of slipped capital femoral epiphysis (see Section 4.8 Adverse Effects (Undesirable Effects), Post-marketing experience).

Urinary system.

In chronic renal insufficiency, the renal function should have decreased below 50% of normal before initiation of therapy. Growth should have been followed for a year preceding initiation of therapy with Omnitrope in order to verify the growth disturbance. Conservative treatment for the renal insufficiency should have been established and should be maintained during treatment. Treatment should be discontinued after renal transplantation.
Growth hormone treatment may represent an increased risk for acute rejection in patients with renal allograft and a history of two or more rejection episodes.

Neoplasms.

Patients with growth hormone deficiency secondary to an intracranial lesion have to be examined frequently for progression or recurrence of the underlying disease process.
Newly diagnosed and recurrent cases of leukaemia have been reported in growth hormone deficient children treated with somatropin. These children had other risk factors for leukaemia. A causal association with somatropin has not been identified.

Critically ill patients.

Two placebo controlled clinical trials of patients in intensive care units have demonstrated an increased mortality among patients suffering from acute critical illness due to complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure who were treated with somatropin in high doses (5.3 mg to 8 mg/day). These types of patients should not be treated with somatropin (see Section 4.3 Contraindications). Because there is no information available on the safety of growth hormone therapy in acutely critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved. In all patients developing other or similar acute critical illness, the possible benefits of treatment with somatropin must be weighed against the potential risk involved.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.3 Contraindications.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant glucocorticoid therapy may inhibit growth and thereby oppose the growth promoting effect of Omnitrope. If glucocorticoid replacement therapy is required, the glucocorticoid dose and compliance have to be monitored carefully to avoid either adrenal insufficiency or inhibition of the growth promoting effects of Omnitrope.
Growth hormone decreases the conversion of cortisone to cortisol and may unmask previously undiscovered central hypoadrenalism or render low glucocorticoid replacement dose ineffective (see Section 4.4 Special Warnings and Precautions for Use).
Data from an interaction study conducted in growth hormone deficient adults, suggest that somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporin). The clinical significance of this is unknown.
Also see Section 4.4 Special Warnings and Precautions for Use, regarding diabetes mellitus, thyroid disorder and corticotropin deficiencies.
Insulin dosage may need to be adjusted when Omnitrope is administered to patients with diabetes mellitus.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No specific study has been conducted in animals to examine the effect of Omnitrope on fertility. However, somatropin is known to have adverse effects on reproduction. Inhibition of reproduction was reported in male and female rats at somatropin doses of 1 mg/kg/day or more, with reduced copulation and conception rates, lengthened or absent oestrus cycles and, at 3.3 mg/kg/day, a lack of responsiveness of females to males and slight reductions in sperm motility and survival. Rat reproduction was unaffected by 0.3 mg/kg/day somatropin, which resulted in a systemic exposure (based on body surface area) of approximately 2 times that anticipated in adult patients at the maximal clinical dose of 0.01 mg/kg/day.
(Category B2)
No specific study has been conducted in animals to examine the reproductive toxicity of Omnitrope. However, somatropin was not teratogenic and did not affect foetal growth at subcutaneous maternal doses up to 3.3 mg/kg/day in rats or 1.3 mg/kg/day in rabbits, which resulted in systemic exposures based on body surface area of approximately 40 times the anticipated maximum clinical exposure.
There is no experience with somatropin during pregnancy, nor has the need for such use been established. Treatment with Omnitrope should be interrupted if pregnancy occurs.
It is not known whether somatropin is excreted in breast milk, but the possibility cannot be excluded. However, absorption of intact protein from the gastrointestinal tract of the infant is extremely unlikely. As a general precaution, treatment with Omnitrope should be interrupted during breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

In general, mild to moderate uncommon (0.1% to 1%) adverse effects related to fluid retention, such as peripheral oedema, face oedema, stiffness in the extremities, arthralgia, myalgia and paraesthesia are observed within the first months of treatment, but they usually subside either spontaneously or with dose reduction.
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of therapy.
The following events have been reported in patients treated with somatropin preparations. See Table 1.
Some cases of leukaemia have been reported in growth hormone deficient children treated with somatropin, but the incidence appears to be similar to that in children without growth hormone deficiency (see Section 4.4 Special Warnings and Precautions for Use).

Post-marketing experience.

In the post-marketing experience, rare cases of sudden death have been reported in patients affected by Prader-Willi syndrome treated with somatropin, although no causal relationship has been demonstrated. Omnitrope is not indicated for use in patients with Prader-Willi syndrome (see Section 4.4 Special Warnings and Precautions for Use).
Slipped capital femoral epiphysis and Legg-Calve-Perthes disease have been reported in children treated with growth hormone.
Rash, pruritus and urticaria have been reported in paediatric patients (frequency uncommon).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

An acute overdose may lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdosing could result in signs and symptoms similar to gigantism or acromegaly, consistent with the known effects of excess exposure to growth hormone.
Treatment is symptomatic and supportive. There is no antidote for somatropin overdose. It is recommended to monitor thyroid function following an overdose.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Human growth hormone (somatropin) is a 191 amino acid polypeptide hormone (molecular weight 22 kilodaltons) normally synthesised and secreted by the somatotropic cells of the anterior lobe of the pituitary gland. The secretion of growth hormone is controlled by two hypothalamic hormones: growth hormone releasing factor (GRF) and growth hormone inhibiting hormone (somatostatin), and is tightly regulated by an integrated system of neural, metabolic and hormonal factors. Growth hormone is present throughout life and its secretion is both age and sex dependent.
Growth hormone binds to specific receptors that have recently been described and identified on hepatocytes, fibroblasts and lymphoid cells. Its known physiological roles are probably due to both direct actions of growth hormone and indirect actions that are mediated by the somatomedins (also called insulin-like growth factors, IGFs).
The somatomedins are themselves peptide hormones whose secretion is stimulated predominantly by the action of growth hormone and include IGF-1 (somatomedin C) and IGF-2. The major site of somatomedin production is the liver but they may also be synthesised at peripheral sites.
Growth hormone has effects not only on growth but also on body composition and metabolism. The following actions have been demonstrated for somatropin:

Skeletal growth.

Somatropin and its mediator IGF-1 stimulate skeletal growth in children with inadequate endogenous secretion of growth hormone. The measurable increase in body length after administration of somatropin results from an effect on the epiphysial plates of long bones. Concentrations of IGF-1 tend to increase during treatment with somatropin.

Cell growth.

It has been shown that there are fewer skeletal muscle cells in short statured children who lack endogenous growth hormone when compared to normal children and that treatment with somatropin results in an increase in both the number and size of muscle cells.

Protein metabolism.

Linear growth is facilitated in part by increased cellular protein synthesis. This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion following the initiation of somatropin therapy.

Carbohydrate metabolism.

Growth hormone is a well known modulator of carbohydrate metabolism. Children with hypopituitarism sometimes experience hypoglycaemia that is improved by somatropin. Large doses of somatropin may impair glucose tolerance.

Lipid metabolism.

Somatropin administration has resulted in lipid mobilisation, reduction in body fat stores and increased plasma free fatty acids in patients with growth hormone deficiency.

Mineral metabolism.

Retention of sodium, potassium and phosphorus is induced by somatropin. Serum concentrations of inorganic phosphate are increased in patients with growth hormone deficiency after therapy with somatropin due to metabolic activity associated with bone growth and increased tubular reabsorption in the kidney. Serum calcium is not significantly altered by somatropin.

Connective tissue metabolism.

Somatropin stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.

Clinical trials.

The efficacy and safety of Omnitrope were compared with Genotropin in a randomised controlled open study involving a total of 89 prepubertal children (49 boys, 40 girls) with growth hormone deficiency. Inclusion criteria were height of < -2 standard deviation score (SDS) for chronological age, spontaneous growth velocity < -1 SDS assessed over an interval of at least 6 months before enrolment, and documented results of two standard pharmacological provocation tests with growth hormone peak < 10 microgram/L.
Forty four children with a mean age of 7.8 years (3.0-13.0 years) received Omnitrope powder for injection and 45 children with a mean age of 7.6 years (2.0-14.0 years) received Genotropin powder for injection. Both Omnitrope and Genotropin were administered subcutaneously at a daily dose of 0.03 mg/kg for 9 months.
The following results of the primary efficacy endpoints, obtained in the intention to treat population, demonstrated a comparable efficacy profile between Omnitrope and Genotropin.
Mean body height at the start of treatment was 113.3 cm ± 13.33 and 109.3 cm ± 15.68 in the Omnitrope and Genotropin groups, respectively. After 9 months of treatment, mean body height was 121.9 cm ± 13.06 and 117.7 cm ± 14.71, showing an increase of 8.6 cm and 8.4 cm, respectively.
Mean height velocity (HV) at the start of treatment was 3.8 cm/year ± 1.23 and 4.0 cm/year ± 0.83 in the Omnitrope and Genotropin groups, respectively. After 9 months of treatment, mean HV was 10.7 cm/year ± 2.57 and 10.7 cm/year ± 2.90, showing an increase of 6.9 cm/year and 6.7 cm/year, respectively.
The mean height standard deviation score (HSDS) at the start of treatment was -3.0 ± 0.72 SDS and -3.1 ± 0.89 SDS in the Omnitrope and Genotropin groups. After 9 months of treatment, mean HSDS had increased to -2.3 ± 0.68 SDS and -2.5 ± 0.73 SDS, respectively.
The mean height velocity standard deviation score (HVSDS) at the start of treatment was -2.4 ± 1.30 in the Omnitrope and -2.3 ± 1.12 in the Genotropin group. Over the 9 months of treatment, patients grew at an average rate of 6.1 ± 3.67 and 5.4 ± 3.16, respectively, above the mean growth rate for the normal population.
Mean levels of the two pharmacodynamic markers IGF-1 and IGFBP3 were also comparable between the two treatment groups.
The study was extended to compare the efficacy and safety of Omnitrope powder for injection with Omnitrope solution for injection. Children were eligible for the study if they had completed 9 months of treatment in the previous study. Forty two children who had received Omnitrope powder for injection continued with the same treatment, whereas 44 children who had previously received Genotropin powder for injection were switched to Omnitrope solution for injection. Both treatments were administered subcutaneously at a daily dose of 0.03 mg/kg for 6 months.
After a total of 15 months of treatment, i.e. 15 months with Omnitrope powder for injection or 9 months with Genotropin powder for injection plus 6 months with Omnitrope solution for injection, body height had increased significantly by an average of 12.7 cm in both groups, to a mean body height of 126.1 cm ± 12.95 and 122.0 cm ± 14.68, respectively.
Average HV after 15 months of treatment was 8.5 cm/year ± 1.80 in the Omnitrope powder for injection group and 8.6 cm/year ± 2.04 in the Omnitrope solution for injection group.
Mean HSDS after 15 months of treatment had increased to -2.0 ± 0.72 SDS in the Omnitrope powder for injection group and to -2.2 ± 0.73 SDS in the Omnitrope solution for injection group.
The mean HVSDS after 15 months of treatment was 3.4 ± 2.55 SDS in the Omnitrope powder for injection group and 3.2 ± 2.89 SDS in the Omnitrope solution for injection group.
To obtain long-term efficacy and safety data on Omnitrope solution for injection, the study was further extended. Children were eligible for the study if they had completed 15 months of treatment in the previous studies. Forty two children who had previously received Omnitrope powder for injection were switched to Omnitrope solution for injection, whereas 44 children who had received Omnitrope solution for injection continued with the same treatment. Both treatments were administered subcutaneously at a daily dose of 0.03 mg/kg for 15 months.
After a total of 30 months, i.e. 15 months with Omnitrope powder for injection plus 15 months with Omnitrope solution for injection or 9 months with Genotropin powder for injection plus 21 months with Omnitrope solution for injection, 78 patients had completed treatment. Body height had increased by an average of 21.3 cm, to a mean body height of 132.6 cm ± 14.01. Average HV after 30 months of treatment was 7.4 cm/year ± 1.60. Mean HSDS had increased to -1.7 ± 0.87 SDS. The mean HVSDS after 30 months of treatment was 2.5 ± 3.25 SDS.
The results obtained in these studies are consistent with other somatropin preparations in the treatment of children with growth hormone deficiency.

5.2 Pharmacokinetic Properties

Absorption.

Maximum somatropin concentrations are reached approximately 4 hours after administration. The elimination half-life is approximately 3 hours. Somatropin serum concentrations return to baseline within 24 hours.

Bioequivalence.

Bioequivalence between Omnitrope powder for injection and Genotropin powder for injection was demonstrated in a double blind, randomised, two way crossover study in 24 healthy volunteers (12 males, 12 females) receiving a single dose of 5 mg somatropin subcutaneously. The pharmacokinetic parameters are summarised in Table 2.
Area under the plasma concentration curve (AUC) and maximum observed plasma concentration (Cmax) were used to test for bioequivalence between Omnitrope powder for injection and Genotropin powder for injection. The standard criterion for bioequivalence was met in that the 90% confidence interval (CI) for the ratio between Omnitrope powder for injection and Genotropin powder for injection was between 0.80 and 1.25. The AUC ratio for Omnitrope powder for injection to Genotropin powder for injection was 1.00, 90% CI [0.96; 1.04] and the Cmax ratio was 1.03, 90% CI [0.94; 1.12].
Bioequivalence between Omnitrope powder for injection and Omnitrope 5 mg/1.5 mL solution for injection was demonstrated in a double blind, randomised, two way crossover study in 24 healthy volunteers (12 males, 12 females) receiving a single dose of 5 mg somatropin subcutaneously. The pharmacokinetic parameters are summarised in Table 3.
Area under the plasma concentration curve (AUC) and maximum observed plasma concentration (Cmax) were used to test for bioequivalence between Omnitrope powder for injection and Omnitrope 5 mg/1.5 mL solution for injection. The standard criterion for bioequivalence was met in that the 90% confidence interval (CI) for the ratio between Omnitrope powder for injection and Omnitrope 5 mg/1.5 mL solution for injection was between 0.80 and 1.25. The AUC ratio for Omnitrope Powder for Injection to Omnitrope 5 mg/1.5 mL solution for injection was 1.00, 90% CI [0.96; 1.03] and the Cmax ratio was 1.01, 90% CI [0.97; 1.06].
In a double blind, randomised, 3 way crossover study in 36 healthy volunteers receiving a single dose of 5 mg somatropin subcutaneously, the bioequivalence between Omnitrope powder for injection, Omnitrope 10 mg/1.5 mL solution for injection and Genotropin 5 mg powder for injection was demonstrated. The pharmacokinetic parameters are summarised in Table 4.
Area under the plasma concentration curve (AUC) and maximum observed plasma concentration (Cmax) were used to test for bioequivalence between Genotropin, Omnitrope powder for injection and Omnitrope 10 mg/1.5 mL solution for injection. The standard criterion for bioequivalence was met in that the 90% confidence interval (CI) for the ratio between these products was between 0.80 and 1.25. The ratios of the means of AUClast and Cmax between these products are presented in Table 5.
In a randomised, double blind, 3 way crossover study in 33 subjects receiving a single dose of 5 mg somatropin subcutaneously the bioequivalence of Omnitrope 15 mg/1.5 mL solution for injection, Omnitrope powder for injection and the reference product Genotropin (sourced in EU) was shown. The results of the study demonstrated that Omnitrope 15 mg/1.5 mL sfi, Omnitrope powder for injection and Genotropin are bioequivalent, based on the primary pharmacokinetic variables AUClast and Cmax.
The pharmacokinetic parameters are summarised in Table 6.
The ratios of AUClast and Cmax were 106.4% and 102.9% for Omnitrope powder for injection compared to Omnitrope 15 mg/1.5 mL sfi with associated 90% CIs of 103.0% to 110.0% and 96.3% to 110.1% respectively.
For the comparison of Omnitrope powder for injection to Genotropin 5 mg/mL, the ratios of AUClast and Cmax were 103.9% and 101.8%, respectively. The associated 90% CIs were 100.5% to 107.4% for AUClast and 95.2% to 108.9% for Cmax.
For the comparison of Omnitrope 10 mg/mL solution for injection to Genotropin 5 mg/mL, the ratios of AUClast and Cmax were 97.6% and 98.9%, respectively. The associated 90% CIs were 94.5% to 100.9% for AUClast and 92.5% to 105.8% for Cmax.
The upper and lower boundaries of the 90% confidence intervals were well within the bioequivalence limits of 80%-125% for all comparisons.

Distribution.

No data available.

Metabolism.

No data available.

Excretion.

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No specific study has been conducted to examine the genotoxic potential of Omnitrope. However, there was no evidence for somatropin genotoxicity in assays for gene mutation in bacteria and mouse lymphoma cells or chromosomal damage in human lymphocytes and rat bone marrow cells.

Carcinogenicity.

Somatropin raises the serum levels of IGF-1. Associations between elevated serum IGF-1 concentrations and risks of certain cancers have been reported in epidemiological studies. Causality has not been demonstrated. The clinical significance of these associations, especially for subjects treated with somatropin who do not have growth hormone deficiency and who are treated for prolonged periods, is not known. Serum IGF-1 levels can be affected by factors other than growth hormone status including nutrition.

6 Pharmaceutical Particulars

6.1 List of Excipients

Omnitrope 5 mg/1.5 mL solution for injection.

Dibasic sodium phosphate heptahydrate, monobasic sodium phosphate dihydrate, poloxamer, mannitol, phosphoric acid, sodium hydroxide and water for injections. Contains benzyl alcohol as preservative.

Omnitrope 5 mg/1.5 mL solution for injection for SurePal 5.

Dibasic sodium phosphate heptahydrate, monobasic sodium phosphate dihydrate, poloxamer, mannitol, phosphoric acid, sodium hydroxide and water for injections. Contains benzyl alcohol as preservative.

Omnitrope 10 mg/1.5 mL solution for injection.

Monobasic sodium phosphate dihydrate, dibasic sodium phosphate heptahydrate, poloxamer, phenol, glycine, phosphoric acid, sodium hydroxide and water for injections.

Omnitrope 10 mg/1.5 mL solution for injection for SurePal 10.

Monobasic sodium phosphate dihydrate, dibasic sodium phosphate heptahydrate, poloxamer, phenol, glycine, phosphoric acid, sodium hydroxide and water for injections.

Omnitrope 15 mg/1.5 mL solution for injection for SurePal 15.

Monobasic sodium phosphate dihydrate, dibasic sodium phosphate heptahydrate, poloxamer, phenol, sodium chloride, phosphoric acid, sodium hydroxide and water for injections.

Omnitrope 1.33 mg powder for injection.

Dibasic sodium phosphate heptahydrate, monobasic sodium phosphate, glycine, sodium hydroxide, hydrochloric acid and water for injections on reconstitution.

Omnitrope 5 mg powder for injection.

Dibasic sodium phosphate heptahydrate, monobasic sodium phosphate, glycine, sodium hydroxide, hydrochloric acid. Each cartridge of solvent contains 1.14 mL of water for injection and 1.5% benzyl alcohol as preservative on reconstitution.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (in a refrigerator).
Do not freeze.
Store in the original package in order to protect from light.

6.5 Nature and Contents of Container

Solution for injection.

Colourless Type 1 glass cartridges.

5 mg/1.5 mL.

Each pack contains 1, 5 or 10 cartridges.

10 mg/1.5 mL.

Each pack contains 1, 5 or 10 cartridges.
Not all presentations may be marketed in Australia.

Solution for injection for SurePal.

Colourless Type 1 glass cartridges (irreversibly integrated in a transparent container called cartridge holder).

5 mg/1.5 mL for SurePal 5.

Each pack contains 1, 5 or 10 cartridges for SurePal 5.

10 mg/1.5 mL for SurePal 10.

Each pack contains 1, 5 or 10 cartridges for SurePal 10.

15 mg/1.5 mL for SurePal 15.

Each pack contains 1, 5 or 10 cartridges for SurePal 15.
Not all presentations may be marketed in Australia.

Powder for injection.

Colourless Type 1 glass vials of Omnitrope and diluent.

1.33 mg.

Each pack contains 1 vial of Omnitrope and 1 vial of diluent.

5 mg.

Each pack contains 8 vials of Omnitrope, 8 cartridges of diluent and 8 transfer needles.
Not all presentations may be marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

N/A.

CAS number.

12629-01-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes