SAIZEN 8 mg/ml INJECTABLE SOLUTION IN CARTRIDGES

Introduction

Package Leaflet: Information for the User

Saizen 8mg/ml solution for injectionin cartridge

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 signs of illness are the same as yours.
• If you get 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 Saizen is and what it is used for
2. What you need to know before you use Saizen
3. How to use Saizen
4. Possible side effects
5. Storage of Saizen

1. Contents of the pack and other information

1. What Saizen is and what it is used for

Saizen is a growth hormone. The main action of Saizen is to increase growth in children and adolescents and to treat adults with growth hormone deficiency.

The growth hormone (somatropin) contained in Saizen is virtually the same as the natural human growth hormone with the difference that it has been produced outside the body by a process called “recombinant DNA technology” (genetic engineering).

Saizen is used:

In children and adolescents:

• for the treatment of children with short stature who have not grown enough because their body does not produce or produces insufficient amounts of growth hormone
• for the treatment of girls who have not grown enough due to gonadal dysgenesis (also called Turner syndrome), confirmed by chromosome analysis
• for the treatment of prepubertal children who have not grown enough due to chronic renal failure, a situation in which the kidneys are damaged
• for the treatment of growth problems in children who were born small and who have not reached normal height by the age of 4 or later.

In adults:

• for the treatment of adults with a pronounced lack of growth hormone (growth hormone deficiency).

This treatment is given to adults with a pronounced growth hormone deficiency that has been medically diagnosed through analysis.

Your doctor or pharmacist will be able to explain why this medicine has been prescribed for you or your child.

2. What you need to know before you use Saizen

Do not use Saizen:

• If you (or your child) are allergic (hypersensitive) to somatropin or any of the other components of this medicine (listed in section 6).
• If you have been informed that your child's bones have stopped growing and that, therefore, they have reached adult height.
• If you have an active tumor (cancer). Tumors must be inactive and you must have finished anti-tumor treatment before starting treatment with Saizen.
• If you (or your child) have diabetes and suffer from an associated eye disease (proliferative or preproliferative diabetic retinopathy).

• If you or your child have a critical acute illness, if you have complications after heart surgery, abdominal surgery, multiple trauma, acute respiratory failure, or similar diseases.

Treatment with Saizen should be interrupted in children with chronic renal failure at the time of kidney transplantation.

Warnings and precautions

Consult your doctor before starting treatment with Saizen.

Treatment with Saizen should be carried out under the regular supervision of a doctor with experience in the diagnosis and treatment of patients with growth hormone deficiency.

Soon after administration of Saizen, you (or your child) may feel shaky or dizzy due to low blood sugar levels. These symptoms will disappear quickly. Your blood sugar levels (or those of your child) may then rise above normal 2-4 hours after administration. Since growth hormone treatment can alter how your body metabolizes sugar, a doctor will regularly measure your blood sugar levels (or those of your child). Somatropin may cause you (or your child) to have high blood sugar.

If you (or your child) are diabetic or a family member has diabetes, your doctor will closely monitor your blood sugar levels and may adjust the treatment for diabetes while being treated with Saizen.

Note that you may need regular eye checks after using this medicine.

Saizen may affect the functioning of the thyroid gland. Your doctor may perform blood tests to determine thyroid hormone levels and prescribe another hormone if you (or your child) have a lack of thyroid hormone.

If you (or your child) are using corticosteroids, you should consult your doctor regularly as you may need to adjust the dose of corticosteroids or Saizen.

Saizen may cause fluid retention in adult patients. This may appear as swelling and pain in muscles or joints. If you have these symptoms, inform your doctor, who may decide to adjust your dose of Saizen.

If you had a tumor during childhood and were treated with Saizen, there is a higher risk of developing a new tumor. If you (or your child) have had a brain disease in the past, such as a tumor, the doctor will regularly examine you (or your child) to check that it has not reappeared.

Rarely, Saizen may cause pancreatitis, which causes severe abdominal and back pain. Please consider this if your child has stomach pain and contact your doctor.

Any child in a phase of rapid growth may develop an increase in the curvature of the spine (scoliosis). During treatment with Saizen, your doctor will assess whether you (or your child) have symptoms of scoliosis.

Some patients have developed brain swelling during treatment with Saizen. If you (or your child) have severe or repeated headaches, vision problems, nausea, and/or vomiting, contact your doctor immediately. In this case, it may be necessary to interrupt treatment with growth hormone, although it can be restarted later. If symptoms of brain swelling reappear, treatment with Saizen should be interrupted.

If the medicine is injected in the same place for a long time, it can damage that area. Therefore, it is essential to change the injection site. Your doctor or pharmacist can comment on which parts of the body should be used (see section 3 How to use Saizen).

Some children with growth hormone deficiency have developed leukemia (an increase in the number of white blood cells), both in those who received growth hormone treatment and in those who did not. However, there is no evidence of an increased incidence of leukemia in patients receiving growth hormone without predisposing factors. No cause-and-effect relationship has been demonstrated with growth hormone treatment.

In children with hormonal or kidney problems, hip problems may appear more frequently. If your child has chronic renal failure, which can occur when the kidneys are damaged, they should be examined periodically to rule out bone disease. It is not clear whether bone disease in children with hormonal or kidney problems is affected by growth hormone treatment. A hip X-ray should be taken before starting treatment. If your child develops a limp or complains of hip or knee pain during treatment with Saizen, inform your doctor.

Treatment with Saizen will be interrupted in children with chronic renal failure at the time of kidney transplantation.

Saizen is not indicated for the long-term treatment of pediatric patients with growth retardation due to genetically confirmed Prader-Willi syndrome unless they also have a diagnosis of growth hormone deficiency. Cases of sleep apnea and sudden death have been reported after starting growth hormone treatment in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection.

Generally, growth hormone should not be used in people who are seriously ill.

If you do not respond to treatment with Saizen, you may have developed antibodies against growth hormone. Your doctor will perform the necessary tests to determine this.

If you are over 60 years old or if you have been using Saizen for a long time, your doctor should monitor you more frequently. Since there is little experience in the treatment of elderly people, as well as in prolonged treatments with Saizen, special caution is required.

Other medicines and Saizen

Tell your doctor or pharmacist if you (or your child) are using, have recently used, or might use any other medicines.

If you (or your child) are using corticosteroids, it is essential to inform your doctor or pharmacist. These medicines may interact with Saizen, so your doctor may need to adjust the dose of these medicines or your dose of Saizen. Corticosteroids are used to treat various diseases, including asthma, allergies, kidney transplant rejection, and rheumatoid arthritis.

If you are taking oral estrogen replacement therapy, the effect of Saizen on growth may be reduced. Therefore, your doctor may need to adjust the dose of Saizen.

If you are being treated with sex hormones, with medicines to control epilepsy (anticonvulsants) or with cyclosporin (a medicine that weakens the immune system after a transplant), you should inform your doctor, as it may be necessary to adjust the dose of these medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

There is insufficient evidence from human studies on the safety of growth hormone treatment during pregnancy and breastfeeding. Treatment with Saizen should be interrupted if you become pregnant.

Driving and using machines

No studies have been conducted on the effects of Saizen on the ability to drive and use machines. Medicines containing somatropin do not affect the ability to drive and use machines.

Important information about some ingredients of Saizen

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

3. How to use Saizen

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

Dose

Your doctor will decide the dose and frequency of administration of Saizen based on your weight or body surface area (or that of your child).

Saizen is recommended to be administered at bedtime.

Children and adolescents:

• Short stature due to lack or insufficient levels of natural growth hormone:

0.7-1.0 mg/m2 body surface area per day or 0.025-0.035 mg/kg body weight per day, by subcutaneous administration (under the skin).

• Growth retardation in girls due to gonadal dysgenesis (Turner syndrome):

1.4 mg/m2 body surface area per day or 0.045-0.050 mg/kg body weight per day, by subcutaneous injection (under the skin).

If your daughter is being treated for Turner syndrome and is also receiving non-androgenic anabolic steroids, she may have a greater growth response. Ask your doctor or pharmacist if you have questions about these medicines.

• Growth retardation in prepubertal children due to chronic renal failure, a situation in which the kidneys are damaged:

1.4 mg/m2 body surface area, which is approximately equal to 0.045-0.050 mg/kg body weight per day, by subcutaneous administration (under the skin).

• Growth problems in children born small:

1 mg/m2 body surface area, approximately equal to 0.035 mg/kg body weight per day, by subcutaneous administration (under the skin).

Adults:

• Growth hormone deficiency in adults:

Initially, low doses of 0.15-0.30 mg per day are recommended, administered by subcutaneous injection (under the skin). Your doctor will gradually adjust the dose. The final recommended dose of growth hormone rarely exceeds 1.0 mg/day. In general, the minimum effective dose that works for you should be administered. Older patients or those who are overweight may require a lower dose.

Method and route of administration

Your doctor will decide the dose and frequency of administration of Saizen based on your weight or body surface area (or that of your child). Saizen should generally be administered daily by subcutaneous injection (under the skin).

Important information

For the administration of Saizen, read the following instructions carefully.

If the medicine is injected in the same place for a long time, it can damage that area. It is essential to change the injection site. Your doctor or pharmacist can comment on which parts of the body should be used. Do not use areas where you notice lumps, hardening, depressions, or pain; inform your doctor or pharmacist of any findings.

Clean the skin at the injection site with water and soap.

The cartridge containing the Saizen solution is ready to be administered with your easypod auto-injector or aluetta pen.

Each Saizen cartridge is identified with a different color and must be used with the aluetta pen identified with the same color to administer the correct dose. The cartridges containing 12 mg of somatropin (red) must be administered with the aluetta 12 pen (red).

The cartridges containing 20 mg of somatropin (yellow) must be used with the aluetta 20 pen (yellow).

Place all the necessary elements for the injection of the solution on a clean surface and wash your hands with water and soap.

The solution should be clear or slightly opalescent, without particles, and without visible signs of deterioration. If the solution contains particles, it should not be injected.

How to perform your daily administration of Saizen

To see the instructions on how to load the cartridge into the easypod auto-injector or aluetta pen and how to inject the Saizen solution, carefully read the corresponding instruction manual provided with each injector. The users for whom the use of easypod is intended are mainly children from 7 years of age to adults. Children should always use the auto-injectors under the supervision of an adult.

Duration of treatment

Your child should stop using this treatment when, as indicated by your doctor, they reach a satisfactory adult height or when their bones have stopped growing. Treatment with Saizen should be interrupted in children with chronic renal failure at the time of kidney transplantation.

In adults, growth hormone deficiency is a lifelong condition and should be treated as such by your doctor.

If you use more Saizen than you should

If you inject too much Saizen, you should inform your doctor, as it may be necessary to slightly change the dose to compensate. Administration of an excessive dose may cause changes in blood sugar levels, which can cause you (or your child) to feel shaky and dizzy. If this happens, contact your doctor as soon as possible.

In case of overdose or accidental ingestion, consult the Toxicology Information Service, telephone 91 562 04 20.

If you forget to use Saizen

If you forget a dose, inform your doctor, as it may be necessary to slightly change the dose to compensate.

If you interrupt treatment with Saizen

Do not interrupt treatment with Saizen without talking to your doctor.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

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

Tell your doctor immediately if you suffer from intense and repeated headaches associated with dizziness (nausea), vomiting, or visual disturbances. These are symptoms of an adverse effect called benign intracranial hypertension and it is rare.

Adverse effects may occur with a certain frequency, which is defined as follows:

• Very frequent: may affect more than 1 in 10 people
• Frequent: may affect up to 1 in 10 people
• Rare: may affect up to 1 in 100 people
• Very rare: may affect up to 1 in 1,000 people
• Frequency not known: the frequency cannot be estimated with the available data

Frequent Adverse Effects:

• Reactions at the injection site such as redness, itching, swelling, rash, hives, pain, inflammation, bleeding, abnormal accumulation of blood outside a blood vessel (hematoma). If this is especially bothersome, you should discuss it with your doctor.
• Local loss of fat tissue under the skin, which can be avoided if the injection site is alternated.
• Carpal tunnel syndrome in adults characterized by persistent tingling, burning sensation, pain, and/or numbness in the fingers, especially the thumb, index finger, and sometimes also the middle finger and ring finger.
• Fluid retention: peripheral edema (swelling), muscle pain, numbness, and tingling, joint pain, and joint disorders in adult patients. These adverse effects usually appear at the start of treatment, are transient, and depend on the dose.
• Headache (isolated).

Rare Adverse Effects:

• Benign intracranial hypertension (increased intracranial pressure around the brain, characterized by headache, nausea, vomiting, double vision, and other visual symptoms).
• Carpal tunnel syndrome in children characterized by persistent tingling, burning sensation, pain, and/or numbness in the fingers, especially the thumb, index finger, and sometimes also the middle finger and ring finger.
• Fluid retention: peripheral edema (swelling), muscle pain, numbness, and tingling, joint pain, and joint disorders in children. These adverse effects usually appear at the start of treatment, are transient, and depend on the dose.
• Increased breast size (one or both breasts may be affected).

Very Rare Adverse Effects:

• Slipped capital femoral epiphysis (a hip problem that starts if the growing end of the thigh bone slips in relation to the hip joint) and avascular necrosis of the femoral head. If your child presents with an unexplained limp and hip or knee pain, contact your doctor or pharmacist.
• Treatment with growth hormone may reduce thyroid hormone levels. Your doctor may perform tests to detect this and, if necessary, prescribe the appropriate treatment.

Adverse Effects of Unknown Frequency:

You (or your child) may experience allergic reactions due to treatment with Saizen.

You (or your child) may experience high insulin levels (hyperinsulinism) since, during treatment with growth hormone, muscle cells, fat cells, and liver cells do not respond properly to insulin (insulin resistance). This condition can result in high blood sugar levels (hyperglycemia).

Rarely, pancreatitis has been described in patients treated with growth hormone.

Some cases of leukemia have been described in a small number of patients with growth hormone deficiency, some of whom were treated with somatropin. However, there is no evidence of an increased incidence of leukemia in patients treated with growth hormone without predisposing factors.

Very rarely, a patient may develop antibodies (a type of protein that helps protect the body) against somatropin. Normally, these are not associated with any adverse effects and do not interfere with growth.

Reporting Adverse Effects:

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects that do not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Saizen

Keep this medicine out of the sight and reach of children.

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

Store the unused Saizen cartridge in the refrigerator (between 2°C-8°C) in the original packaging to protect it from light. Do not freeze.

After the first injection, use within the next 28 days.

After the first injection, the Saizen cartridge, the easypod auto-injector that contains the Saizen cartridge, or the aluetta pen that contains the Saizen cartridge, should be stored in the refrigerator (2°C-8°C) for a maximum of 28 days, of which up to 7 days can be stored outside the refrigerator at 25°C or below. When the Saizen cartridge has been stored outside the refrigerator for up to 7 days, it should be returned to the refrigerator and used within a maximum of 28 days after the first injection.

When using the easypod auto-injector or the aluetta pen, the cartridge remains in the device.

Medicines should not be thrown away through wastewater or household waste. 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 will help protect the environment.

6. Package Contents and Additional Information

Saizen Composition

The active ingredient is somatropin (recombinant human growth hormone) 12 or 20 mg.

The other components are: sucrose, poloxamer 188, phenol, citric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injectable preparations.

Product Appearance and Package Contents

Saizen 8 mg/ml is a clear to slightly opalescent injectable solution in a pre-filled cartridge (type 1 glass) with a piston stopper (rubber) and a folded cap (aluminum and rubber). The cartridge with 12 mg of somatropin is marked with a colored label (red). The cartridge with 20 mg of somatropin is marked with a colored label (yellow).

The packs of 1 and 5 cartridges contain 1.50 ml of solution (12 mg of somatropin) or 2.50 ml of solution (20 mg of somatropin).

Only some pack sizes may be marketed.

Marketing Authorization Holder:

Merck, S.L.

C/ María de Molina, 40

28006 Madrid, Spain

Information line: 900 200 400

Manufacturer:

Merck Serono S.p.A., Modugno, Bari, Italy.

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom with the following names:

Saizen: Austria, Belgium, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Luxembourg, Norway, Portugal, Romania, Slovakia, Spain, Sweden, United Kingdom.

Date of the last revision of this leaflet:December 2023

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