Saizen

Package leaflet: Information for the user

Saizen 5.83 mg/ml solution for injection in cartridge

somatropin
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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. How to store Saizen
6. 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 promote growth in children and adolescents and to treat adults with growth hormone deficiency.
The growth hormone (somatropin) contained in Saizen is nearly identical to natural human growth hormone, except that it is produced outside the body through a process known as "recombinant DNA technology" (genetic engineering).
Saizen is used:
In children and adolescents:

• to treat short stature in children who have not grown due to a lack or insufficient production of growth hormone;
• to treat growth failure in girls associated with gonadal dysgenesis (also known as Turner syndrome), confirmed by chromosomal analysis;
• to treat growth failure due to chronic renal insufficiency, a condition in which the kidneys are damaged, in pre-pubertal children;
• to treat growth disturbance in children born small who have not achieved normal height by the age of 4 years or later.

In adults:

• to treat adults with severe growth hormone deficiency (growth hormone deficiency). This therapy is administered to adults diagnosed with a severe growth hormone deficiency confirmed by specific medical testing.

Your doctor or pharmacist can explain why this medicine has been prescribed for you or your child.

2. What you should know before using Saizen

Do not use Saizen

• If you (or your child) are allergic (hypersensitive) to somatropin or to any of the other ingredients of this medicine (listed in section 6).
• If you have been told that your child's bones have stopped growing and that he or she has reached final height.
• If you have active tumor growth (cancer). Tumors must be inactive and anti-tumor therapy must be completed before starting treatment with Saizen.
• If you (or your child) have diabetes and also suffer from an associated eye disease (proliferative or preproliferative diabetic retinopathy).
• If you or your child suffer from an acute critical illness, complications following open-heart surgery, abdominal surgery, multiple accidental traumas, acute respiratory failure, or similar conditions.

In children with chronic kidney disease, treatment with Saizen must be discontinued at the time of kidney transplantation.

Warnings and precautions

Talk to your doctor before using Saizen.

Treatment with Saizen must be carried out under the continuous supervision of a doctor specialized in diagnosing and treating patients with growth hormone deficiency.

Shortly after administration of Saizen, you (or your child) may experience tremors or dizziness due to a drop in blood glucose levels. These symptoms disappear quickly. Within 2–4 hours after administration, your (or your child’s) blood glucose levels may rise above normal values. Since treatment with growth hormone may alter the way your body handles sugars, your (or your child’s) blood glucose levels will be monitored regularly by the doctor. Somatropin may cause an increase in your (or your child’s) blood glucose levels.

If you (or your child) have diabetes or a family history of diabetes, the doctor will closely monitor blood glucose levels and may adjust diabetes therapy during treatment with Saizen.

Be aware that you may need to undergo regular eye examinations after taking this medicine.

Saizen may impair your thyroid function. The doctor may perform blood tests to check thyroid hormone levels and may prescribe additional thyroid hormone if a thyroid hormone deficiency is detected in you (or your child).

If you (or your child) are taking corticosteroids, you should consult your doctor regularly, as you may need adjustments in the dosage of corticosteroids or Saizen.

Saizen may cause fluid retention in adult patients. This may manifest as swelling and joint or muscle pain. If these symptoms occur, inform your doctor, who may decide to adjust the dose of Saizen.

If you had a tumor during childhood and were treated with Saizen, there is an increased risk of developing a new tumor. If you (or your child) have previously suffered from brain disorders, such as a tumor, the doctor will examine you (or your child) regularly to monitor for recurrence of such conditions.

Rarely, Saizen may cause inflammation of the pancreas, causing severe pain in the abdomen and back. Please consider this possibility and contact your doctor, especially if the child complains of stomach pain.

An increase in spinal curvature on both sides (scoliosis) may progress in any child during rapid growth. During treatment with Saizen, your doctor will monitor you (or your child) for signs of scoliosis.

During treatment with Saizen, some patients may develop cerebral edema. If you (or your child) experience severe or recurrent headache, visual disturbances, nausea and/or vomiting, contact your doctor immediately. In such cases, treatment with growth hormone may need to be discontinued temporarily, but may be resumed later. If symptoms of cerebral edema recur, treatment with Saizen must be stopped.

If the medicine is injected repeatedly at the same site over a long period, it may damage the affected area. It is therefore necessary to rotate injection sites. Your doctor or pharmacist will explain which parts of the body should be used (see section 3 How to use Saizen).

There have been reports of cases of leukemia (increased white blood cell count) in children with growth hormone deficiency, both treated and untreated with growth hormone. However, there is no evidence of an increased incidence of leukemia in patients treated with growth hormone in the absence of predisposing factors. No causal relationship with growth hormone administration has been demonstrated.

Children with hormonal or kidney problems may more frequently develop hip problems. If your child has chronic kidney failure—a condition in which the kidneys are damaged—he or she should be monitored periodically for bone disorders. It is not certain whether bone disorders in children with hormonal or kidney problems may be influenced by growth hormone therapy. A radiological examination of the hip should be performed before starting therapy. If your child develops a limp or complains of hip or knee pain during treatment with Saizen, inform your doctor.

In children with chronic kidney failure, treatment with Saizen must be discontinued at the time of kidney transplantation.

Saizen is not indicated for long-term treatment of pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome unless growth hormone deficiency has also been diagnosed. There have been reports of sleep apnea and sudden death after initiation of growth hormone therapy in pediatric patients with Prader-Willi syndrome who also had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unrecognized respiratory infection.

Growth hormone should generally not be administered to patients with severe illnesses.

If you do not respond to Saizen therapy, you may have developed antibodies to growth hormone. Your doctor will perform appropriate tests to determine this.

If you are over 60 years of age or have been on Saizen treatment for a long time, you will require more frequent monitoring by your doctor. Because data on treatment in elderly patients and on long-term Saizen therapy are limited, particular caution is required.

Other medicines and Saizen

Tell your doctor or pharmacist if you (or your child) are taking, have recently taken, or might take any other medicines.

If you (or your child) are taking corticosteroids, it is important to inform your doctor or pharmacist. These medicines may interact with Saizen, and therefore your doctor may need to adjust their dosage or that of Saizen. Corticosteroids are used to treat various conditions such as asthma, allergies, kidney transplant rejection, and rheumatoid arthritis.

If you are taking oral estrogen replacement therapy, this may reduce the growth-promoting effect of Saizen. Therefore, your doctor may need to adjust your Saizen dose.

If you are being treated with sex hormones, antiepileptic drugs (anticonvulsants), or cyclosporine (a medicine that suppresses the immune system after transplantation), inform your doctor, as dose adjustments of these medicines may be necessary.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

There are insufficient clinical data in humans regarding the safety of growth hormone treatment during pregnancy or breastfeeding. Saizen must be discontinued if pregnancy occurs.

Driving and using machines

No studies have been conducted on the effects of Saizen on the ability to drive vehicles or operate machinery.

Medicines containing somatropin do not affect the ability to drive vehicles or use machinery.

Important information about some ingredients of Saizen

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

3. How to use Saizen

Always use this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

Dosage
The dose and frequency of administration of Saizen will be determined by your doctor and will depend on your body surface area or body weight (or that of your child).

Saizen is recommended to be administered before going to bed.

Children and adolescents:

• Short stature due to deficiency or insufficient levels of natural growth hormone: 0.7–1.0 mg/m² of body surface area per day, or 0.025–0.035 mg/kg of body weight per day, administered subcutaneously (under the skin).
• Growth failure in girls with gonadal dysgenesis (Turner syndrome): 1.4 mg/m² of body surface area per day, or 0.045–0.050 mg/kg of body weight per day, administered subcutaneously (under the skin). If your daughter is being treated for Turner syndrome and is simultaneously taking non-androgenic anabolic steroids, the growth response may be enhanced. Ask your doctor or pharmacist for further information about these medicines.
• Growth failure in prepubertal children caused by chronic renal insufficiency, a condition in which the kidneys are damaged: 1.4 mg/m² of body surface area per day, approximately equivalent to 0.045–0.050 mg/kg of body weight per day, administered subcutaneously (under the skin).
• Growth problems in children born small: 1 mg/m² of body surface area, approximately equivalent to 0.035 mg/kg of body weight per day, administered subcutaneously (under the skin).

Adults:

• Growth hormone deficiency in adults: at the beginning of therapy, low daily doses of 0.15–0.3 mg are recommended, administered subcutaneously (under the skin). The dose should be gradually adjusted by the doctor. The final recommended dose of growth hormone is rarely above 1.0 mg/day. In general, the lowest effective dose for you should be administered. Lower doses may be required in elderly or overweight patients.

Method and route of administration
The dose and frequency of administration of Saizen will be determined by your doctor and will depend on your body weight or body surface area (or that of your child). Normally, Saizen should be administered daily by subcutaneous injection (under the skin).

Important information
Carefully read the following instructions before administering Saizen.

If the medicine is injected repeatedly into the same area over a long period, this may cause damage to that area. It is important to rotate the injection site. Your doctor or pharmacist can advise you on which part of the body to use. Do not use areas that show lumps, hardening, skin depressions, or pain; in such cases, inform your doctor or pharmacist. Clean the injection site with water and soap.

The cartridge containing the Saizen solution is ready for use with the easypod autoinjector or the aluetta pen injector.

Each Saizen cartridge has an identifying color and must be used with the corresponding color of the aluetta pen injector to ensure correct dosing. The cartridge containing 6 mg of somatropin (blue) must be used with the aluetta 6 pen injector (blue).

Prepare all necessary materials for the injection on a clean surface and wash your hands thoroughly with water and soap.

The solution should be from clear to slightly opalescent, free from particles, and show no visible signs of deterioration. Do not inject the solution if it contains particles.

How to perform your daily Saizen injections
For instructions on how to insert the cartridge into the easypod autoinjector or aluetta pen injector and how to inject the Saizen solution, carefully read the user manual provided in the packaging of each injector. The primary users of the easypod are children aged 7 years and older and adults. Use of these devices by children must always be supervised by an adult.

Duration of treatment
Your child should stop this treatment upon reaching a satisfactory adult height or when the doctor determines that their bones can no longer grow. In children with chronic renal insufficiency, Saizen treatment should be discontinued at the time of kidney transplantation. In adults, growth hormone deficiency is a permanent condition and should be treated accordingly by the doctor.

If you use more Saizen than you should
If an excessive amount of Saizen is injected, inform your doctor, as minor adjustments to the dosage may be necessary to compensate. Injecting too much medication may alter blood glucose levels, which may cause you (or your child) to feel shaky or dizzy. If this occurs, contact your doctor as soon as possible.

If you forget to take Saizen
If you miss a dose, inform your doctor, as minor dosage adjustments may be necessary to compensate.

If you stop using Saizen
Do not stop administering Saizen without first consulting your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Immediately inform your doctor if you experience severe and recurring headaches associated with feeling unwell (nausea), vomiting, or vision disturbances. These are symptoms of an uncommon side effect known as benign intracranial hypertension.

Side effects may occur with varying frequencies as listed below:

• Very common: may affect more than 1 in 10 people
• Common: may affect up to 1 in 10 people
• Uncommon: may affect up to 1 in 100 people
• Rare: may affect up to 1 in 1,000 people
• Very rare: may affect up to 1 in 10,000 people
• Not known: frequency cannot be estimated from the available data.

Common side effects:
Reactions at the injection site such as redness, itching, swelling, rash, hives, pain, inflammation, bleeding, or abnormal accumulation of blood outside a blood vessel (haematoma). If these symptoms are particularly bothersome, discuss them with your doctor.
Local reduction of fatty tissue under the skin, which can be avoided by rotating injection sites.
Carpal tunnel syndrome in adults, characterized by persistent pain described as a stabbing or burning sensation, pain and/or numbness in the fingers, particularly affecting the thumb, index finger, and sometimes the middle and ring fingers.
Fluid retention: peripheral oedema (swelling), muscle pain, numbness and tingling, joint pain and joint disorders in adults. These side effects usually occur early in treatment, are transient, and are dose-dependent.
Headache (isolated).

Uncommon side effects:
Benign intracranial hypertension (increased pressure around the brain, characterized by headache, nausea, vomiting, double vision, and other visual disturbances).
Carpal tunnel syndrome in children, characterized by persistent pain described as a stabbing or burning sensation, pain and/or numbness in the fingers, particularly affecting the thumb, index finger, and sometimes the middle and ring fingers.
Fluid retention: peripheral oedema (swelling), muscle pain, numbness and tingling, joint pain and joint disorders in children. These side effects usually occur early in treatment, are transient, and are dose-dependent.
Breast enlargement (one or both sides may be affected).

Very rare side effects:
Slipped capital femoral epiphysis (a hip disorder occurring when the upper end of the thigh bone slips off the ball-shaped joint of the hip). Avascular necrosis of the femoral head. If your child experiences difficulty walking or pain in the hip or knee, contact your doctor or pharmacist.
Growth hormone treatment may reduce thyroid hormone levels. Your doctor can test for this and, if necessary, prescribe appropriate treatment.

Side effects with frequency not known:
You (or the child) may experience allergic reactions due to treatment with Saizen.
You (or your child) may experience increased insulin levels (hyperinsulinism), as muscle, fat, and liver cells do not respond adequately to insulin during growth hormone treatment (insulin resistance). This condition may lead to high blood glucose levels (hyperglycaemia).
Pancreatitis (inflammation of the pancreas) has been reported rarely in patients treated with growth hormone.
Leukaemia has been reported 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 leukaemia in patients treated with growth hormone in the absence of predisposing factors.
Very rarely, a patient may develop antibodies (a type of protein that helps the body defend itself) against somatropin. These are usually not associated with any side effects and generally do not interfere with growth.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Saizen

Keep this medicine out of the sight and reach of children.
Do not use Saizen after the expiry date stated on the cartridge after the word "Exp.". The expiry date refers to the last day of that month.
Store unused Saizen cartridges in the refrigerator (2°C–8°C) in the original packaging to protect the medicine from light. Do not freeze.
After the first injection, use the product within 28 days.
After the first injection, the Saizen cartridge, the easypod autoinjector containing the Saizen cartridge, or the aluetta pen injector containing the Saizen cartridge must be stored in the refrigerator (2°C–8°C) for up to 28 days; within this period, it may be kept outside the refrigerator at a temperature not exceeding 25°C for up to 7 days. If stored outside the refrigerator for up to 7 days, the Saizen cartridge must be returned to the refrigerator and used within 28 days of the first injection.
When using the easypod autoinjector or the aluetta pen injector, the cartridge remains in the device.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Saizen contains
The active substance is somatropin (recombinant human growth hormone) 6 mg.
The excipients are sucrose, poloxamer 188, phenol, citric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

Description of the appearance of Saizen and contents of the pack
Saizen 5.83 mg/ml is an injectable solution, from clear to slightly opalescent, in a pre-filled cartridge (type I glass) with a rubber plunger stopper and an aluminum crimped cap (aluminum and rubber), containing a nominal volume of 1.03 ml of solution (6 mg of somatropin). The cartridge containing 6 mg of somatropin is labeled with a blue label.
Pack sizes of 1 and 5 cartridges.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Merck Serono S.p.A. - Via Flaminia 970-972, 00189 Rome, Italy

Manufacturer
Merck Serono S.p.A. – Via delle Magnolie 15 (loc. Frazione Zona Industriale), 70026 Modugno (Bari), Italy

This medicinal product is authorized in the European Economic Area (EEA) and in the United Kingdom
under 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

Package leaflet: Information for the user

Saizen 8 mg/ml solution for injection in cartridge

somatropin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

7. What Saizen is and what it is used for
8. What you need to know before using Saizen
9. How to use Saizen
10. Possible side effects
11. How to store Saizen
12. 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 promote growth in children and adolescents, and to treat growth hormone deficiency in adults.
The growth hormone (somatropin) contained in Saizen is nearly identical to natural human growth hormone, except that it is produced outside the body through a process called "recombinant DNA technology" (genetic engineering).
Saizen is used:
In children and adolescents:

• to treat short stature in children who have not grown due to a lack or insufficient production of growth hormone;
• to treat growth failure in girls associated with gonadal dysgenesis (also known as Turner syndrome), confirmed by chromosomal analysis;
• to treat growth failure due to chronic renal insufficiency, a condition in which the kidneys are damaged, in prepubertal children;
• to treat growth disorders in children born small who have not achieved normal height by the age of 4 years or thereafter.

In adults:

• to treat adults with a pronounced deficiency of growth hormone (growth hormone deficiency). This therapy is administered to adults diagnosed with severe growth hormone deficiency confirmed by specific medical testing.

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

2. What you should know before using Saizen

Do not use Saizen

• If you (or your child) are allergic (hypersensitive) to somatropin or any of the other ingredients of this medicine (listed in section 6).
• If you have been told that your child's bones have stopped growing and that he or she has reached final height.
• If you have active tumour disease (cancer). Tumours must be inactive and anti-tumour therapy must be completed before starting treatment with Saizen.
• If you have diabetes and also have an associated eye disease (proliferative or preproliferative diabetic retinopathy).
• If you or your child suffer from acute critical illness, complications following open-heart surgery, abdominal surgery, accidental multiple traumas, acute respiratory failure, or similar conditions.

In children with chronic kidney disease, treatment with Saizen must be discontinued at the time of kidney transplantation.

Warnings and precautions

Talk to your doctor before using Saizen.

Treatment with Saizen must be carried out under the constant supervision of a doctor specialised in the diagnosis and treatment of patients with growth hormone deficiency.

Shortly after administration of Saizen, you (or your child) may experience tremor or dizziness due to a drop in blood glucose levels. These symptoms disappear quickly. Within 2–4 hours after administration, your (or your child's) blood glucose levels may rise above normal values. Since treatment with growth hormone may alter the way your body handles sugars, your doctor will regularly monitor your (or your child's) blood glucose levels. Somatropin may cause an increase in your (or your child's) blood glucose levels.

If you (or your child) have diabetes or a family history of diabetes, your doctor will closely monitor blood glucose levels and may adjust diabetes therapy during treatment with Saizen.

Be aware that regular eye examinations may be necessary after taking this medicine.

Saizen may affect the function of your thyroid gland. Your doctor may perform blood tests to check thyroid hormone levels and may prescribe another hormone if you (or your child) develop thyroid hormone deficiency.

If you (or your child) are taking corticosteroids, you should consult your doctor regularly, as you may need adjustments in the dosage of either the corticosteroid or Saizen.

Saizen may cause fluid retention in adult patients. This may appear as swelling and joint or muscle pain. If these symptoms occur, inform your doctor, who may decide to adjust the dose of Saizen.

If you had a tumour during childhood and were treated with Saizen, there is an increased risk of developing a new tumour. If you (or your child) have previously had brain disorders, such as a tumour, your doctor will examine you (or your child) regularly to monitor for recurrence of such conditions.

Rarely, Saizen may cause inflammation of the pancreas, leading to severe abdominal and back pain. Please consider this possibility and contact your doctor, especially if the child complains of stomach pain.

An increase in spinal curvature on both sides (scoliosis) may progress in any child during rapid growth. During treatment with Saizen, your doctor will monitor you (or your child) for signs of scoliosis.

During treatment with Saizen, some patients may develop cerebral edema. If you (or your child) experience severe or recurring headache, visual disturbances, nausea and/or vomiting, contact your doctor immediately. In such cases, treatment with growth hormone may need to be discontinued, although it may be restarted later. If symptoms of cerebral edema recur, treatment with Saizen must be stopped.

If the medicine is injected repeatedly into the same site over a long period, this may cause damage to the area. It is therefore necessary to rotate injection sites. Your doctor or pharmacist will explain which body areas should be used (see section 3 How to use Saizen).

There have been reports of cases of leukaemia (increased number of white blood cells) in children with growth hormone deficiency, both treated and untreated with growth hormone. However, there is no evidence of an increased incidence of leukaemia in patients treated with growth hormone in the absence of predisposing factors. No causal relationship with growth hormone administration has been established.

Children with hormonal or kidney problems may be more prone to hip problems. If your child has chronic kidney insufficiency, a condition in which the kidneys are damaged, he or she should be monitored periodically for bone disorders. It is not certain whether bone disorders in children with hormonal or kidney problems may be influenced by growth hormone therapy. A radiological examination of the hip should be performed before starting therapy. If your child develops a limp or complains of hip or knee pain during treatment with Saizen, inform your doctor.

In children with chronic kidney failure, treatment with Saizen must be discontinued at the time of kidney transplantation.

Saizen is not indicated for long-term treatment of paediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome unless growth hormone deficiency has also been diagnosed. There have been reports of sleep apnoea and sudden death after initiation of growth hormone therapy in paediatric patients with Prader-Willi syndrome who also had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnoea, or unidentified respiratory infection.

Growth hormone should generally not be administered to patients with serious illnesses.

If you do not respond to Saizen therapy, you may have developed antibodies to growth hormone. Your doctor will perform appropriate tests to determine this.

If you are over 60 years of age or have been on Saizen treatment for a long time, you will be monitored more frequently by your doctor. Because data on treatment in elderly patients and long-term Saizen therapy are limited, particular caution is required.

Other medicines and Saizen

Tell your doctor or pharmacist if you (or your child) are taking, have recently taken, or might take any other medicines.

If you (or your child) are taking corticosteroids, it is important to inform your doctor or pharmacist. These medicines may interact with Saizen, and therefore your doctor may need to adjust their dosage or that of Saizen. Corticosteroids are used to treat various conditions such as asthma, allergies, kidney transplant rejection, and rheumatoid arthritis.

If you are taking oral oestrogen replacement therapy, this may reduce the growth-promoting effect of Saizen. Therefore, your doctor may need to adjust your Saizen dose.

If you are taking sex hormones, antiepileptic drugs (anticonvulsants), or cyclosporine (a medicine that suppresses the immune system after transplantation), inform your doctor, as dose adjustments of these medicines may be necessary.

Pregnancy and breastfeeding

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

There are insufficient clinical data in humans regarding the safety of growth hormone treatment during pregnancy or breastfeeding. Saizen must be discontinued if pregnancy occurs.

Driving and using machines

No studies have been conducted on the effects of Saizen on the ability to drive vehicles or operate machinery.

Medicines containing somatropin do not affect the ability to drive vehicles or operate machinery.

Important information about some ingredients of Saizen

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

3. How to use Saizen

Always use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Dosage
The dose and frequency of administration of Saizen will be determined by your doctor and will depend on your body surface area or body weight (or that of your child).

It is recommended to administer Saizen before going to bed.

Children and adolescents:

• Short stature due to deficiency or insufficient levels of natural growth hormone: 0.7–1.0 mg/m² of body surface area per day, or 0.025–0.035 mg/kg body weight per day, administered subcutaneously (under the skin).
• Growth deficiency in girls with gonadal dysgenesis (Turner syndrome): 1.4 mg/m² of body surface area per day, or 0.045–0.050 mg/kg body weight per day, administered subcutaneously (under the skin). If your daughter is being treated for Turner syndrome and is simultaneously taking non-androgenic anabolic steroids, the growth response may increase. Ask your doctor or pharmacist for further information about these medicines.
• Growth deficiency in prepubertal children caused by chronic renal insufficiency, a condition in which the kidneys are damaged: 1.4 mg/m² of body surface area per day, approximately equivalent to 0.045–0.050 mg/kg body weight per day, administered subcutaneously (under the skin).
• Growth problems in children born small: 1 mg/m² of body surface area, approximately equivalent to 0.035 mg/kg body weight per day, administered subcutaneously (under the skin).

Adults:

• Growth hormone deficiency in adults:

At the beginning of therapy, low daily doses of 0.15–0.3 mg administered subcutaneously (under the skin) are recommended. This dose should be gradually adjusted by the doctor. The recommended final dose of growth hormone is rarely higher than 1.0 mg/day. In general, the lowest effective dose for you should be administered. Lower doses may be required in elderly or overweight patients.

Method and route of administration
The dose and frequency of administration of Saizen will be determined by your doctor and will depend on your body weight or body surface area (or that of your child). Saizen is normally administered daily by subcutaneous injection (under the skin).

Important information
Carefully read the following instructions for administering Saizen.
If the medicine is injected repeatedly into the same area over a long period, this may cause damage to the site. It is important to rotate the injection site. Your doctor or pharmacist can advise you on which areas of the body to use. Do not use areas that show lumps, hardening, skin depressions, or pain; if such symptoms occur, inform your doctor or pharmacist. Clean the injection site with water and soap.

The cartridge containing the Saizen solution is ready for use with the easypod auto-injector or with the aluetta pen injectors.

Each Saizen cartridge has a specific colour coding and must be used with the corresponding colour of the aluetta pen injector to ensure correct dosing. The cartridge containing 12 mg of somatropin (red) must be used with the aluetta 12 pen injector (red). The cartridge containing 20 mg of somatropin (yellow) must be used with the aluetta 20 pen injector (yellow).

Prepare all necessary materials for the injection on a clean surface and wash your hands with water and soap.

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

How to perform your daily Saizen injections
For instructions on how to insert the cartridge into the easypod auto-injector or into the aluetta pen injectors and on how to inject the Saizen solution, carefully read the user manual included in the packaging of each injector. The primary users of the easypod are children aged 7 years and older and adults. Use of these devices by children must always be supervised by an adult.

Duration of treatment
Your child should stop this treatment upon reaching a satisfactory adult height or when the doctor determines that their bones can no longer grow. In children with chronic renal insufficiency, Saizen treatment should be discontinued at the time of kidney transplantation. In adults, growth hormone deficiency is a permanent condition and must be treated accordingly by the doctor.

If you use more Saizen than you should
If an excessive amount of Saizen is injected, inform your doctor, as minor adjustments to the dosage may be needed to compensate. Injecting too much medicine may alter blood glucose levels, which may cause you (or your child) to feel shaky and dizzy. If this occurs, contact your doctor as soon as possible.

If you forget to take Saizen
If you miss a dose, inform your doctor, as minor adjustments to the dosage may be needed to compensate.

If you stop using Saizen
Do not stop administering Saizen without first consulting your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Contact your doctor immediately if you experience severe and recurring headaches associated with feeling unwell (nausea), vomiting or vision disturbances. These are symptoms of a non-common side effect known as benign intracranial hypertension.
Side effects may occur with varying frequencies as listed below:

• very common: may affect more than 1 in 10 users
• common: may affect up to 1 in 10 users
• not common: may affect up to 1 in 100 users
• rare: may affect up to 1 in 1,000 users
• very rare: may affect up to 1 in 10,000 users
• not known: frequency cannot be estimated from the available data.

Common side effects:
Reactions at the injection site such as redness, itching, swelling, rash, hives, pain, inflammation, bleeding, or abnormal accumulation of blood outside a blood vessel (haematoma). If these symptoms are particularly bothersome, discuss them with your doctor.
Local reduction of fatty tissue under the skin, which can be avoided by rotating injection sites.
Carpal tunnel syndrome in adults, characterised by persistent pain described as a stabbing or burning sensation, pain and/or numbness in the fingers, particularly affecting the thumb, index finger, and sometimes also the middle and ring fingers.
Fluid retention: peripheral oedema (swelling), muscle pain, numbness and tingling, joint pain and joint disorders in adults. These side effects usually appear during the initial phase of treatment, are transient and dose-dependent.
Headache (isolated episode).

Uncommon side effects:
Benign intracranial hypertension (increased intracranial pressure around the brain, characterised by headache, nausea, vomiting, double vision and other visual symptoms).
Carpal tunnel syndrome in children, characterised by persistent pain described as a stabbing or burning sensation, pain and/or numbness in the fingers, particularly affecting the thumb, index finger, and sometimes also the middle and ring fingers.
Fluid retention: peripheral oedema (swelling), muscle pain, numbness and tingling, joint pain and joint disorders in children. These side effects usually appear during the initial phase of treatment, are transient and dose-dependent.
Breast enlargement (may affect one or both sides).

Very rare side effects:
Slipped capital femoral epiphysis (a hip disorder occurring when the upper end of the thigh bone slips off the ball of the hip joint) and avascular necrosis of the femoral head. If your child has difficulty walking or experiences hip or knee pain, contact your doctor or pharmacist.
Growth hormone treatment may reduce levels of thyroid hormone. This can be tested by your doctor, and if necessary, your doctor will prescribe appropriate treatment.

Side effects with frequency not known:
You (or the child) may experience allergic reactions due to treatment with Saizen.
You (or your child) may experience increased insulin levels (hyperinsulinaemia), as muscle, fat and liver cells may not respond adequately to insulin during growth hormone treatment (insulin resistance). This condition may lead to high blood glucose levels (hyperglycaemia).
Pancreatitis (inflammation of the pancreas) has been reported rarely in patients treated with growth hormone.
Leukaemia has been reported 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 leukaemia in patients treated with growth hormone in the absence of predisposing factors.
Very rarely, a patient may develop antibodies (a type of protein that helps the body defend itself) against somatropin. These are usually not associated with any side effects and generally do not interfere with growth.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Saizen

Keep this medicine out of the sight and reach of children.
Do not use Saizen after the expiry date stated on the cartridge after the word "Exp." The expiry date refers to the last day of that month.
Store unused Saizen cartridges in the refrigerator (2°C–8°C) in the original packaging to protect the medicine from light. Do not freeze.
After the first injection, use the product within 28 days.
After the first injection, the Saizen cartridge, the easypod autoinjector containing the Saizen cartridge, or the aluetta pen injector containing the Saizen cartridge must be stored in the refrigerator (2°C–8°C) for up to 28 days. Within this time period, it may be kept outside the refrigerator at a temperature not exceeding 25°C for up to 7 days. If stored outside the refrigerator for up to 7 days, the Saizen cartridge must be returned to the refrigerator and used within 28 days of the first injection.
When using the easypod autoinjector or the aluetta pen injector, the cartridge remains in the device.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Saizen contains
The active substance is somatropin (recombinant human growth hormone).
The excipients are sucrose, poloxamer 188, phenol, citric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

Description of the appearance of Saizen and package contents
Saizen 8 mg/ml is an injectable solution ranging from clear to slightly opalescent, contained in a pre-filled cartridge (Type I glass) with a plunger stopper (rubber) and a screw cap (aluminum and rubber). The cartridge containing 12 mg of somatropin is labelled with a red label. The cartridge containing 20 mg of somatropin is labelled with a yellow label.
Pack sizes of 1 and 5 cartridges contain either 1.50 ml of solution (12 mg of somatropin) or 2.50 ml of solution (20 mg of somatropin).
Not all pack sizes may be marketed.

Marketing Authorization Holder
Merck Serono S.p.A. - Via Flaminia 970-972, 00189 Rome, Italy

Manufacturer
Merck Serono S.p.A. – Via delle Magnolie 15 (loc. Frazione Zona Industriale), 70026 Modugno (Bari), Italy

This medicinal product is authorized in the European Economic Area and the United Kingdom
under 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