Prospect: Information for the User

Saizen 8mg/ml injectable solution in cartridge

somatropin

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Content ofprospect

1. What is Saizen and for what it is used
2. What you need to know before starting to use Saizen
3. How to use Saizen
4. Possible adverse effects
5. Storage of Saizen

6. Content of the package and additional information

Saizen is a growth hormone. The primary 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 practically 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 due to their body not producing or producing insufficient levels of growth hormone
• for the treatment of girls who have not grown enough due to gonadal dysgenesis (also known as Turner syndrome), confirmed by chromosome analysis
• for the treatment of prepubertal children who have not grown enough due to chronic renal insufficiency, 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 an analysis.

The doctor or pharmacist may explain why this medication has been prescribed for you or your child.

No use Saizen:

• If you (or your child) are allergic (hypersensitive) to somatropin or any of the other components of this medication (including those 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 completed antitumor treatment before starting treatment with Saizen.
• If you (or your child) have diabetes and have an associated eye disease (proliferative or preproliferative diabetic retinopathy).

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

Treatment with Saizen should be discontinued in children with chronic kidney disease at the time of kidney transplant.

Warnings and precautions

Consult your doctor before starting to use 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.

Shortly 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 your child's) may rise above normal 2-4 hours after administration. Since treatment with growth hormone can alter how your body metabolizes sugar, a doctor will regularly measure your blood sugar levels (or your child's). Somatropin may cause an increase in blood sugar levels.

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 diabetes treatment while you are being treated with Saizen.

Be aware that you may need regular eye checks after using this medication.

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 they detect a lack of thyroid hormone in you (or your child).

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

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

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 in the past any disease affecting the brain, for example a tumor, your doctor will regularly examine you (or your child) to check that it has not recurred.

Very rarely, Saizen may cause pancreatitis, which causes severe pain in the abdomen and back. Please consider this if your child experiences stomach pain and contact your doctor.

Any child in rapid growth phases may develop an increase in curvature of the spine (scoliosis). During treatment with Saizen, your doctor will evaluate if you (or your child) present symptoms of scoliosis.

Some patients have presented brain swelling during treatment with Saizen. If you (or your child) experience severe headache or repeated headaches, vision problems, nausea, and/or vomiting, contact your doctor immediately. In this case, it may be necessary to discontinue growth hormone treatment, although it may be reinstated later. If symptoms of brain swelling recur, treatment with Saizen should be discontinued.

If the medication is injected in the same place for a long period, it may damage this area. Therefore, it is essential to change the injection site. Your doctor or pharmacist can advise you on which body parts to use (see section 3 How to use Saizen).

Some children with growth hormone deficiency have developed leukemia (an increase in white blood cells), both with and without treatment with growth hormone. 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, bone problems may appear more frequently. If your child has chronic kidney disease, which may appear when the kidneys are damaged, they should be examined regularly to rule out bone disease. It is unclear whether bone disease in children with hormonal or kidney problems is affected by growth hormone treatment. Before starting treatment, a hip X-ray should be performed. If your child develops a limp or complains of hip or knee pain during Saizen treatment, inform your doctor.

Treatment with Saizen will be discontinued in children with chronic kidney disease at the time of kidney transplant.

Saizen is not indicated for the long-term treatment of pediatric patients with growth delay 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 severely ill individuals.

If you do not respond to Saizen treatment, 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 have been using Saizen for a long time, your doctor should monitor you more frequently. Since there is little experience with the treatment of elderly individuals, as well as with prolonged Saizen treatment, special caution is required.

Other medications and Saizen

Informyour doctor or pharmacist if you (or your child) are using, have used recently, or may need to use any other medication.

If you (or your child) are using corticosteroids, it is essential to inform your doctor or pharmacist. These medications may interact with Saizen, so your doctor may need to adjust the dose of these medications or your Saizen dose. Corticosteroids are used to treat various conditions, 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 Saizen dose.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

Driving and operating machinery

No studies have been conducted on the effects of Saizen on driving and operating machinery. Medications containing somatropin do not affect driving and operating machinery.

Important information about some Saizen ingredients

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

Follow exactly the administration instructions of this medication as indicated by your doctor.In case of doubt, consult your doctor or pharmacist again.

Dose

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

It is recommended to administer Saizen at bedtime.

Children and adolescents:

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

0.7–1.0mg/m2of body surface area per day or 0.025-0.035mg/kg of body weight per day, by subcutaneous injection (under the skin).

• Delayed growth in girls due to gonadal dysgenesis (Turner syndrome):

1.4mg/m2of body surface area per day or 0.045-0.050mg/kg of body weight per day, by subcutaneous injection (under the skin).

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

• Delayed growth in prepubertal children due to chronic renal insufficiency, a condition in which the kidneys are damaged:

1.4mg/m2of body surface area, which is approximately equal to 0.045-0.050mg/kg of body weight per day, by subcutaneous injection (under the skin).

• Growth problems in small-for-gestational-age children:

1mg/m2of body surface area, approximately equal to 0.035mg/kg of body weight per day, by subcutaneous injection (under the skin).

Adults:

• Growth hormone deficiency in adults:

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

Method and route of administration

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

Important information

To administer Saizen, read the following instructions carefully.

If the medication is injected in the same place for a long period, it may damage this area.It is essential to change the location where the injection is made. Your doctor or pharmacist can discuss with you which part of the body to use. Do not use areas where you notice lumps, indurations, 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 autoinjector or alzet pump.

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

Cartridges containing 20mg of somatropin (yellow) must be used with the alzet pump 20 (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 must 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 Saizen administration

To see the instructions on how to load the cartridge into the easypod autoinjector or alzet pump and how to inject the Saizen solution, read the corresponding manual carefully provided with each injector. Users intended for the easypod are mainly children from 7 years of age to adults. Children must always use the autoinjectors under the supervision of an adult.

Treatment duration

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. You should interrupt the treatment with Saizen in children with chronic renal insufficiency 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, inform your doctor as it may be necessary to adjust the dose slightly to compensate. The administration of an excessive dose may cause changes in blood sugar levels, which may cause you (or your child) to experience tremors and dizziness. If this occurs, contact your doctor as soon as possible.

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

If you forget to use Saizen

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

If you interrupt the treatment with Saizen

Do not interrupt the treatment with Saizen without consulting your doctor.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Inform your doctor immediately if you experience severe and repeated headaches associated with dizziness (nausea), vomiting, or visual disturbances. These are symptoms of a side effect called benign intracranial hypertension and are rare.

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

• 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
• Frequency not known: the frequency cannot be estimated with the available data

Common side effects:

• Reactions at the injection site such as redness, itching, swelling, rash, urticaria, pain, inflammation, bleeding, and abnormal accumulation of blood outside a blood vessel (hematoma).If this is especially bothersome, discuss it with your doctor.
• Local loss of subcutaneous fat, which can be prevented by alternating the injection site.
• 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 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 side effects usually appear at the beginning of treatment, are transient, and dose-dependent.
• Headache (isolated).

Uncommon side 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 the middle finger and ring finger.
• Fluid retention: peripheral edema (swelling), muscle pain,numbness and tingling,joint pain, and joint disorders in children. These side effects usually appear at the beginning of treatment, are transient, and dose-dependent.
• Breast enlargement (may affect one or both breasts).

Very rare side effects:

• Slipped capital femoral epiphysis (a hip problem that starts if the growth end of the femur bone slips out of place with respect to the hip joint) and avascular necrosis of the femoral head.If your child experiences unexplained limping 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 it and, if necessary, prescribe the appropriate treatment.

Side effects of unknown frequency:

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

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

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

Some cases of leukemia have been described in a reduced 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 type of side effect and do not interfere with growth.

Reporting of side effects:

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

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

Use within 28 days after the first injection.

After the first injection, the Saizen cartridge, the easypod autoinjector containing the Saizen cartridge, or the Alzet pump containing the Saizen cartridge, must be stored in the refrigerator (2°C–8°C) for a maximum of 28 days, of which up to 7 days may be stored at 25°C or below 25°C. When the Saizen cartridge has been stored outside the refrigerator for up to 7 days, it must be returned to the refrigerator and used within a maximum of 28 days after the first injection.

When using the easypod autoinjector or the Alzet pump, the cartridge is left in the device.

Medicines should not be disposed of through the drains or in the trash. Dispose of the packaging and unused medicines at the SIGRE collection point at the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and unused medicines. By doing so, you will help protect the environment.

Composition of Saizen

The active principle is somatropin (human recombinant 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.

Appearance of the product and content of the container

Saizen 8 mg/ml is a transparent to slightly opalescent injectable solution in a preloaded cartridge (type 1 glass) with a rubber stopper and a folded capsule (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 boxes 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 sizes of packaging may be commercially available.

Marketing Authorization Holder:

Merck, S.L.

C/ María de Molina, 40

28006 Madrid, Spain

Information line: 900 200 400

Responsible for manufacturing:

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.

Revision date of this leaflet: December 2023

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es