ZOMACTON 4 mg POWDER AND SOLVENT FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Zomacton 4 mg powder and solvent for solution for injection

Somatropin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Zomacton is and what it is used for
2. What you need to know before you use Zomacton
3. How to use Zomacton
4. Possible side effects
5. Storage of Zomacton
6. Contents of the pack and other information

1. What Zomacton is and what it is used for

Zomacton contains the active substance somatropin, also known as growth hormone. Growth hormone is produced naturally in the body and has a very important function in growth. Zomacton contains somatropin obtained in a pharmaceutical manufacturing facility.

Zomacton is indicated for the long-term treatment of:

• Children with short stature due to insufficient production of growth hormone

Short stature associated with Turner Syndrome (a genetic disorder that affects women).

2. What you need to know before you use Zomacton

Do not use Zomacton

• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6).
• in children with closed epiphyses (when bone growth is complete)
• do not use Zomacton and inform your doctor if you have an active tumor (cancer). Tumors must remain inactive and you must have finished your anti-tumor treatment before starting treatment with Zomacton
• in premature or newborn children due to the presence of benzyl alcohol as an excipient
• in patients who are seriously ill due to complications, for example, open-heart or abdominal surgery, multiple trauma, or respiratory failure
• in children with chronic kidney disease after kidney transplant

Warnings and precautions

• Zomacton, containing benzyl alcohol as an excipient, may cause toxic and allergic reactions in children under 3 years of age and should not be administered to premature or newborn children.
• Patients with Prader-Willi syndrome should not be treated with Zomacton unless they also have growth hormone deficiency.
• Treatment with Zomacton should be initiated and directed always by a specialist doctor, with experience in the diagnosis of patients with growth hormone deficiency.
• If you have a family history of diabetes mellitus, your blood sugar levels should be analyzed at intervals by your doctor. If you are diabetic, you will require strict control of blood glucose and your dose will need to be adjusted to maintain diabetic control. Your doctor will inform you if necessary.

• If you are a patient with growth hormone deficiency as a consequence of an intracranial injury, you should be examined frequently to see the evolution or recurrence of the disease. If this is confirmed, your doctor will inform you if you need to interrupt treatment with Zomacton
• Please consult your doctor if you develop symptoms or signs of relapse due to a previous malignant disease.
• If you are receiving glucocorticoid replacement therapy, you should consult your doctor regularly as it may be necessary to adjust your glucocorticoid dose.
• If you develop any of the following while being treated with Zomacton, contact your doctor or nearest assistance department urgently:
• severe or repeated headaches
• vision problems
• nausea and/or vomiting

• Treatment with Zomacton may lead to thyroid hormone deficiency, which may require replacement therapy. To control this, your doctor will carry out periodic checks to ensure that your thyroid gland is functioning correctly.
• Some children with growth hormone deficiency have developed leukemia (an increase in the number of white blood cells in the blood), having received or not received growth hormone treatment. However, there is no evidence that the incidence of leukemia is increased in patients without risk factors treated with growth hormone. No cause-and-effect relationship has been proven with growth hormone treatment.
• Please consult your doctor immediately if you develop limping or hip or knee pain.
• If you suffer from complications after surgery, trauma, or acute respiratory failure, consult your doctor.
• If you require surgery, are seriously injured in an accident, or are seriously ill, your doctor will review your treatment.
• Zomacton may cause pancreatitis, which causes severe abdominal and back pain. If you or your child develop stomach pain after administering Zomacton, consult your doctor.

Use in athletes

This medicine contains somatropin, which may produce a positive result in doping tests.

Use of Zomacton with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

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Patients treated with glucocorticoids should carefully adjust their dose, as glucocorticoids may inhibit the gradual growth effect of somatropin. If you are being treated with steroids due to insufficient ACTH (adrenocorticotropic hormone) production, inform your doctor.

Androgens, estrogens, and anabolic steroids may accelerate bone maturation and therefore may reduce the final height increase.

Diabetic patients may need to adjust their insulin dose, as somatropin may induce a state of insulin resistance.

Tell your doctor if you are being treated with regularly prescribed medication, e.g., steroids, epilepsy medication, or immunosuppressive medication.

Pregnancy and breastfeeding

There is no experience with the use in pregnant women. Zomacton should not be used during pregnancy. It is unknown whether Zomacton passes into breast milk. Zomacton should not be used during breastfeeding.

Driving and using machines

Zomacton has no or negligible influence on the ability to drive or use machines.

Zomacton contains benzyl alcohol

This medicine should not be administered to premature or newborn children because it contains 9 mg/ml of benzyl alcohol. It may cause toxic and allergic reactions in children under 3 years of age.

This medicine contains less than 23 mg (1 mmol) of sodium per dose, and is therefore essentially 'sodium-free'.

3. How to use Zomacton

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor or nurse will decide with you the most suitable method of administration and will provide you with instructions for use according to the method used. Your doctor or nurse will inform you of the correct dose for you. The dose is administered subcutaneously (under the skin) with a syringe or with a device with a needle, Ferring-Pen.

Posology:

Growth hormone deficiency in children

Your doctor will calculate the exact dose for you, based on your body weight. Generally, a dose of 0.17-0.23 mg per kg of body weight per week is recommended. This weekly amount can be divided into six or seven doses, corresponding to a daily injection of 0.02-0.03 mg per kg of body weight. The maximum recommended weekly dose is 0.27 mg per kg of body weight, equivalent to daily injections of up to approximately 0.04 mg per kg of body weight.

Turner Syndrome (only women)

Your doctor will calculate the exact dose for you, based on your body weight. Generally, a dose of 0.33 mg per kg of body weight per week is recommended. This weekly amount can be divided into 6-7 doses, corresponding to a daily injection of 0.05 mg per kg of body weight.

Reconstitution instructions:

The powder should be dissolved only with the solvent provided.

Two concentrations can be prepared depending on the volume of solvent used. Your doctor will inform you which concentration to use.

• For administration with a syringe or Ferring-Pen, use 1.3 ml of solvent for a concentration of 3.3 mg/ml (taking into account the total content of the vial, which is more than 4 mg). The reconstituted powder and solvent for solution for injection should be administered with a syringe.
• For administration using only a syringe, use 3.2 ml of solvent for a concentration of 1.3 mg/ml (taking into account the total content of the vial, which is more than 4 mg). The reconstituted powder and solvent for solution for injection should be administered with a syringe.

Reconstitution should be carried out in accordance with good practice guidelines, particularly with regard to asepsis.

1. Wash your hands.

2 a. Attach the needle to the graduated syringe.

2 b. Remove the protective cap from the vial.

• Clean the top of the vial with an alcohol swab. Do not touch the rubber stopper after cleaning.

1. Break the top of the solvent ampoule. Remove the plastic that wraps the needle. Make sure the plunger is fully pushed before inserting the needle into the ampoule.

Slowly withdraw the required volume into the syringe.

1. Place the needle in the center of the cleaned rubber stopper and inside the vial, and slowly inject the solvent into the vial, directing the liquid jet against the glass wall to avoid foaming.

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1. The vial should be gently rotated until the contents are completely dissolved to obtain a clear and colorless solution.

Since the powder contains mainly proteins, avoid rough shaking of the vial.

If the solution is cloudy or contains particles after mixing, the vial and its contents should be discarded. In case of cloudiness after refrigeration, allow the solution to reach room temperature (25°C). If cloudiness persists or discoloration appears, discard the vial and its contents.

The solution should be used within 14 days of reconstitution if stored in the refrigerator.

Any unused solution from the vial should be discarded at the end of the 14-day storage period.

Administration instructions

The clear and transparent solution should then be administered subcutaneously as shown in clinical use with a syringe or Ferring-Pen.

After reconstitution, the following steps should be performed for injection.

1. Wash your hands
2. The top of the vial should be cleaned with an alcohol swab to avoid contamination of its contents. Do not touch the rubber stopper after cleaning
3. Hold the vial upside down, keeping the top of the needle below the surface of the medication. Gently pull the plunger until the prescribed amount of medication fills the syringe. If you do not have enough medication for a full dose, reconstitute a new vial to make up the difference.
4. With the needle still in the inverted vial, gently tap the syringe to loosen any air bubbles.
5. Remove the needle from the vial and carefully replace the needle cap until you are ready to inject.
6. Thoroughly clean the injection site with alcohol.
7. Check that the syringe contains the correct dose.
8. Remove the needle cap and hold the syringe in the same way you would hold a pencil.
9. With your free hand, gently pinch the skin around the injection site between your fingers.
10. Insert the needle into the tissue under the skin surface at an angle of 45° to 90° to reduce discomfort.
11. Holding the syringe in place, slowly push the plunger until the syringe is empty
12. Quickly withdraw the needle and apply pressure to the injection site with a sterile swab. Discard the needle and syringe in a puncture-resistant container.

Do not share your syringes, needles, or vials with anyone else. You may infect them or get an infection from them.

Any unused product or waste material should be disposed of in accordance with local requirements.

The Ferring Pen (device with a needle) is not included in the packaging.

Specific instructions for use of the Ferring Pen are provided in the leaflet that comes with the injector.

If you use more Zomacton than you should

An overdose may cause hypoglycemia (low blood sugar) and subsequently hyperglycemia (high blood sugar).

In case of overdose, contact your doctor or nearest hospital immediately or call the Toxicology Information Service, telephone 915 620 420, indicating the medicine and the amount used. The effects of repeated overdosing are unknown.

If you forget to use Zomacton

If you forget a dose, do not worry. Continue normally and administer the next dose at your usual time.

You may experience hypoglycemia (low blood sugar). Although the long-term effectiveness of the treatment will not be affected, you should consult your doctor if this happens to you.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Subcutaneous administration of growth hormone may cause fat loss or gain at the injection site. It is therefore recommended to frequently change the injection site. In rare cases, patients developed skin pain or itching at the injection site.

Very Common Adverse Effects (may affect more than 1 in 10 patients treated):

Only adults:

• Swelling due to fluid retention, especially in the hands and feet (Edema)
• Slightly increased blood sugar levels (Hyperglycemia)
• Joint pain (Arthralgia)
• Muscle pain (Myalgia)
• Headache
• Numbness, tingling, burning, or prickling sensation on the skin (Paresthesia)

Common Adverse Effects (may affect up to 1 in 10 patients treated):

Children and adults:

• Hypothyroidism
• Immune reaction to growth hormone, which may appear in a blood test (antibody formation)
• Headache
• Increased muscle tone stiffness (Hypertonia)

Only children:

• Swelling due to fluid retention, especially in the hands and feet (Edema, peripheral edema)
• Reactions at the injection site
• Weakness (Asthenia)
• Modified glucose tolerance
• Joint pain (Arthralgia)
• Muscle pain (Myalgia)

Only adults:

• Stiffness in the legs and/or arms
• Difficulty falling asleep and/or difficulty staying asleep (Insomnia)

Uncommon Adverse Effects (may affect up to 1 in 100 patients treated):

Children and adults:

• Anemia
• High pulse rate (Tachycardia)
• Dizzy sensation (Vertigo)
• Double vision (Diplopia)
• Papilla edema
• Vomiting, abdominal pain, flatulence, nausea
• Weakness
• Atrophy at the injection site, bleeding at the injection site, lump at the injection site, hypertrophy
• Low blood sugar levels (Hypoglycemia)
• Hyperphosphatemia (high levels of phosphorus in the blood)
• Muscle atrophy
• Bone pain
• Carpal tunnel syndrome
• Malignant neoplasia, neoplasia
• Somnolence
• Involuntary eye movements (Nystagmus)
• Personality disorders
• Urinary incontinence, hematuria (blood in the urine), polyuria (increased urine volume), increased urination frequency, urinary anomalies
• Reactions at the injection site (including lipodystrophy, skin atrophy, exfoliative dermatitis, urticaria, hirsutism, skin hypertrophy)
• Increased breast size (Gynecomastia)

Only children:

• Stiffness in the legs and/or arms

Only adults:

• High blood pressure (Hypertension)

Rare Adverse Effects (may affect up to 1 in 1,000 patients treated):

Children and adults:

• Diarrhea
• Abnormal kidney function tests
• Type 2 Diabetes Mellitus
• Tingling or numbness in certain areas of the body (Neuropathy)
• Fluid retention around the brain (manifested as repeated or intense headache, blurred vision, and nausea and/or vomiting)

Only children:

• High blood pressure (Hypertension)
• Difficulty falling asleep and/or difficulty staying asleep (Insomnia)
• Numbness, tingling, burning, or prickling sensation on the skin (Paresthesia)

Very Rare Adverse Effects (may affect up to 1 in 10,000 patients treated):

Only children:

• Leukemia (the occurrence seems to be no more frequent than in children in the general population)

Reporting of Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: http://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Zomacton

Keep out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging, after CAD. The expiration date is the last day of the month indicated.

Store in the refrigerator at 2°C - 8°C; keep in the original packaging to protect it from light.

After reconstitution, the solution can be stored for a maximum of 14 days in the refrigerator (2°C-8°C). Keep the vial in a vertical position.

Any unused solution from the vial must be discarded at the end of the 14-day storage period.

In case of turbidity after refrigeration, allow the solution to reach room temperature (25°C). If turbidity persists, or coloration appears, discard the vial and its contents.

Medicines should not be thrown away through the drains or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Zomacton Composition

The active ingredient is somatropin: 4 mg in a vial, corresponding to a concentration of 1.3 mg/ml or 3.3 mg/ml after reconstitution.

The other components are:

Powder: Mannitol

Solvent: 9 mg/ml of benzyl alcohol, sodium chloride, and water for injectable preparations

Zomacton contains less than 1 mmol of sodium (23 mg) per dose, so it is considered essentially "sodium-free".

Product Appearance and Package Contents.

Zomacton is a powder and solvent for injectable solution.

Powder in a vial (4 mg of somatropin) and solvent in an ampoule (3.5 ml) in three types of packaging:

• packaging of 1, 5, or 10 vials, or
• with a syringe and needle.

Package of 5 vials

Not all packaging is marketed.

The powder is white to off-white in color. After reconstitution, the solution is clear and transparent

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Ferring S.A.U.

C/ del Arquitecto Sánchez Arcas nº3, 1º

28040 Madrid

Spain

Manufacturer:

Ferring GmbH

Wittland 11, D-24109 Kiel

Germany

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Austria ZOMACTON 4 mg - Powder and solvent for solution for injection

Belgium Zomacton

Denmark Zomacton

Finland Zomacton

France Zomacton 4 mg

Germany Zomacton 4 mg

Greece Zomacton

Ireland Zomacton

Italy Zomacton

Luxembourg Zomacton

Netherlands Zomacton 4 mg

Portugal Zomacton

Spain Zomacton

Sweden Zomacton

United Kingdom (Northern Ireland) Zomacton

Date of the last revision of this prospectus: September 2021.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/