Prospect: information for the user

INCRELEX 10 mg/ml injectable solution

Mecasermin

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect thoroughly before starting to use this medicine, 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 medicine has been prescribed only to you and should not be given to other people even if they have the same symptoms, 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.

1. What you need to know before starting to use INCRELEX
2. How to use INCRELEX

1. Possible adverse effects
2. Storage of INCRELEX
3. Contents of the package and additional information

No use INCRELEX

• If you currently have any tumor or abnormal growth, whether cancerous or non-cancerous
• If you have had cancer in the past

• If you have any condition that may increase the risk of developing cancer
• If you are allergic (hypersensitive) to mecasermin or to any of the other ingredients of this medication (including those listed in section 6).
• In newborns or premature infants because it contains benzyl alcohol.

Warnings and precautions

There is an increased risk of developing tumors (both cancerous and non-cancerous) in children and adolescents treated with INCRELEX. Since mecasermin may interfere with cancer development, inform your doctor immediately if, during treatment, or after treatment, any new tumor, skin lesion, or unexpected symptom appears.

Consult your doctor or pharmacist before starting to use INCRELEX

• If you suffer from a lateral deviation of the spine (scoliosis). It is advisable to monitor the progression of scoliosis.
• If you develop a limp or pain in the knee or hip

• If you present an increase in the size of the tonsils (hypertrophic tonsils). It is advisable to undergo periodic checks.
• If you present symptoms indicating increased intracranial pressure (hypertension), such as visual changes, headache, nausea, and/or vomiting; consult your doctor.

• If you experience a localized reaction at the injection site or a generalized allergic reaction to INCRELEX. Go to the doctor as soon as possible if you develop a localized skin rash. Seek immediate medical attention if you have a generalized allergic reaction (hives, breathing difficulties, fainting, or collapse and general feeling of discomfort).

• If you have stopped growing (the bone growth plates have closed). In this case, INCRELEX cannot help you grow and should not be used.

Children under 2 years

This medication has not been studied in children under 2 years, therefore, it is not recommended.

Other medications and INCRELEX

Inform your doctor or pharmacist if you are taking or have recently taken, or may need to take any other medication.

Inform your doctor especially if you are being treated with insulin or other antidiabetic medications.

You may need to adjust the dose of these medications.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

For all fertile women, a negative pregnancy test is recommended before starting treatment with mecasermin. It is also recommended that all fertile women use suitable contraceptive measures during treatment.

Treatment with mecasermin should be suspended if pregnancy occurs.

Mecasermin should not be administered to a breastfeeding mother.

Driving and operating machinery

Mecasermin may cause hypoglycemia (very frequent adverse effect, see section 4) that may affect your ability to drive and operate machinery, as your ability to concentrate or react may be reduced.

You should avoid any high-risk activities (e.g. driving, etc.) in the 2-3 hours following the administration of the dose, especially at the beginning of treatment with INCRELEX and until a dose of INCRELEX that does not produce adverse effects that make these activities a risk is found.

INCRELEX contains benzyl alcohol and sodium

INCRELEX contains benzyl alcohol as a preservative that may cause toxic and allergic reactions in infants and children up to 3 years of age.

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

Follow exactly the administration instructions for this medication as indicated by your doctor.

Consult your doctor or pharmacist if you have any doubts.

The normal dose is 0.04 to 0.12 mg per kg of patient weight administered twice a day.

See the "Instructions for use" that appear at the end of this leaflet.

Inject INCRELEX just below the skin a little before or after a meal or snack, as it may have insulin-like hypoglycemic effects and therefore may decrease blood sugar levels (see hypoglycemia in section 4). Do not inject the dose of INCRELEX if you cannot eat for any reason. Do not attempt to compensate for the missed dose by administering double the dose the next time. The next dose should be administered as usual, with a meal or snack.

Inject INCRELEX just below the skin in some point of the arm, leg, abdominal area (abdomen) or buttocks. Never inject into a vein or muscle. Change the injection site each time.

Do not use INCRELEX if it is not transparent and colorless.

Treatment with mecasermin is a long-term treatment. Consult your doctor for more information.

If you use more INCRELEX than you should

Mecasermin, like insulin, may decrease blood sugar levels (see hypoglycemia in section 4).

If you have injected more INCRELEX than recommended, contact your doctor immediately.

A acute overdose may cause hypoglycemia (low glucose concentration in blood).

The treatment of acute mecasermin overdose should focus on reversing hypoglycemia. Food or sugary drinks should be ingested. If the patient is not sufficiently conscious to take sugary drinks, a intramuscular injection of glucagon may be necessary to reverse hypoglycemia. Your doctor or nurse will teach you how to inject glucagon.

Prolonged overdose may cause an increase in size of certain body parts (e.g., hands, feet, facial areas) or excessive growth of the entire body. If you suspect a prolonged overdose, contact your doctor immediately.

If you forgot to use INCRELEX

Do not take a double dose to compensate for the missed doses.

If you have missed a dose, the next dose should not be increased to compensate. The next dose should be administered as usual, with a meal or snack.

If you interrupt treatment with INCRELEX

Discontinuing or prematurely stopping mecasermin treatment may reduce the success of growth therapy. Ask your doctor before stopping treatment.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If you experience side effects, consult your doctor or pharmacist, even if they are side effects that do not appear in this leaflet.

The most frequently reported side effects with mecasermin are: low blood sugar (hypoglycemia), vomiting, reactions at the injection site, headache, and middle ear infections. Severe allergic reactions have also been reported with INCRELEX. If you experience any of these side effects, follow the advice given for each side effect in the following sections.

Unknown frequency (frequency cannot be estimated from available data)Cancerous and non-cancerous tumors

In patients treated with INCRELEX, an increase in the appearance of cancerous and non-cancerous tumors has been reported.The risk of developing these tumors may be higher if INCRELEX is used for a pathology other than that indicated in Section 1 or at a dose higher than recommended in Section 3.

Severe allergic reactions (anaphylaxis)

Generalized urticaria, difficulty breathing, drowsiness, facial and/or throat inflammation have been reported after the use of mecasermin. If you develop a severe allergic reaction, you must immediately discontinue INCRELEX and seek urgent medical assistance.

Severe allergic reactions have also been reported locally at the injection site (itching, urticaria).

Hair loss (alopecia)

With the use of mecasermin, hair loss has also been reported.

Very common (may affect more than 1 in 10 people)

Low blood sugar (hypoglycemia)

Mecasermin may decrease blood sugar levels. Signs of low blood sugar are: drowsiness, fatigue, restlessness, hunger, irritability, concentration problems, sweating, nausea, and rapid or irregular heartbeats.

Severe hypoglycemia can cause unconsciousness, seizures/epileptic fits, or death. Discontinue INCRELEX immediately and seek urgent medical assistance if you develop seizures/epileptic fits or unconsciousness.

If you take INCRELEX, you should avoid participating in high-risk activities (such as intense physical activity) 2 to 3 hours after INCRELEX injection, especially at the start of INCRELEX treatment.

Before starting treatment with INCRELEX, your doctor or nurse will explain how to treat hypoglycemia. You should always have a source of sugar, such as orange juice, glucose gel, sweets, or milk, available in case of hypoglycemia symptoms. In case of severe hypoglycemia, if you do not respond and cannot take a sugary drink, you should administer a glucagon injection. Your doctor or nurse will teach you how to administer the injection. The glucagon injection increases blood glucose levels.

It is essential that you follow a balanced diet that includes, in addition to sugary foods, proteins, and fats such as meat and cheese.

Enlargement at the injection site (tissue at the injection site increases in size) and hematomas

This can be prevented by changing the injection site each time (rotation of the injection site).

Gastrointestinal system

With mecasermin treatment, cases of vomiting and upper abdominal pain have been reported.

Infections

In children treated with mecasermin, middle ear infections have been observed.

Musculoskeletal system

With mecasermin treatment, cases of joint pain and limb pain have been reported.

Nervous system

With mecasermin treatment, cases of headache have been reported.

Common (may affect up to 1 in 10 people):

Seizures

With mecasermin treatment, cases of seizures (fits) have been reported.

With mecasermin treatment, cases of dizziness and tremors have also been reported.

Cardiac anomalies

With mecasermin treatment, cases of rapid pulse and abnormal heart sounds have been reported.

Hyperglycemia (high blood sugar)

With mecasermin treatment, cases of high blood sugar have also been reported.

Enlargement of the tonsils/adenoids

Mecasermin may increase the size of the tonsils/adenoids. Signs of an increase in tonsil size include: snoring, difficulty breathing or swallowing, sleep apnea (a disorder in which brief episodes of suspension of breathing occur during sleep) or presence of fluid in the middle ear, in addition to middle ear infections. Sleep apnea may cause excessive daytime sleepiness. Consult your doctor if these symptoms are bothersome. Your doctor should regularly examine your tonsils.

Enlargement of the thymus

With mecasermin treatment, an increase in thymus size (a specialized organ of the immune system) has been observed.

Papilledema

During mecasermin treatment, your doctor or an optician may observe inflammation of the back of the eye (due to increased pressure in the brain).

Deafness (hearing loss)

With mecasermin treatment, cases of deafness (hearing loss), ear pain, and fluid in the middle ear have been reported. Inform your doctor if you develop hearing problems.

Worsening of scoliosis (caused by rapid growth)

If you have scoliosis, you will need to undergo regular examinations to check if the curvature of the spine has increased. With mecasermin treatment, cases of muscle pain have also been reported.

Reproductive system

With mecasermin treatment, cases of breast enlargement have been reported.

Gastrointestinal system

With mecasermin treatment, cases of abdominal pain have been reported.

Changes in skin and capillaries

With mecasermin treatment, cases of skin thickening, moles, and capillary texture alteration have been reported.

Reactions at the injection site

Reactions reported with mecasermin treatment include pain, irritation, bleeding, hematoma, redness, and hardening. Reactions at the injection site can be prevented by changing the injection site each time (rotation of the injection site).

Uncommon (may affect up to 1 in 100 people)

Increased intracranial pressure (hypertension)

INCRELEX may sometimes cause a temporary increase in intracranial pressure. Possible symptoms of increased intracranial pressure include visual changes, headache, nausea, and/or vomiting. Inform your doctor immediately if you experience any of these symptoms. Your doctor will check if it is due to increased intracranial pressure. If this is the case, your doctor may decide to suspend or temporarily reduce mecasermin treatment. Mecasermin can be restarted when the episode has passed.

Cardiac anomalies

In some patients treated with mecasermin, the heart examination (echocardiogram) has shown an increase in heart muscle size and abnormalities in heart valve function. Your doctor may perform an echocardiogram before, during, and after mecasermin treatment.

Reactions at the injection site

With mecasermin treatment, reactions have been reported that include skin rash, swelling, and fatty lumps. Reactions at the injection site can be prevented by changing the injection site each time (rotation of the injection site).

Weight gain

With mecasermin treatment, cases of weight gain have been reported.

Other uncommon side effects with mecasermin treatment include depression, nervousness.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse,

even if it is a possible side effect that does not appear in this leaflet. You can also

report them directly through thenational reporting system included in theAppendix V.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 this medication after the expiration date that appears on the box and label after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep the vial perfectly closed to protect it from light.

After first use, the vial may be stored for up to 30 days between 2 °C and 8 °C.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of containers and medications that are no longer needed. This will help protect the environment.

Composition of INCRELEX

• The active ingredient is mecasermin. One milliliter contains 10 mg of mecasermin. Each vial contains 40 mg of mecasermin.
• The other components are: benzyl alcohol, sodium chloride, polisorbate 20, glacial acetic acid, sodium acetate, and water for injection (see section 2 “INCRELEX contains benzyl alcohol and sodium”).

Appearance of the product and contents of the pack

INCRELEX is a transparent and colourless injectable solution supplied in a closed glass vial with a stopper and a cap. The vial contains 4 ml of solution.

Size of pack: 1 vial.

Marketing authorisation holder and responsible person for manufacturing

Marketing authorisation holder:

Ipsen Pharma

65, quai Georges Gorse

92100 Boulogne-Billancourt

France

Responsible person for manufacturing:

Beaufour Ipsen Industrie

Rue d'Ethe Virton

28100 Dreux

France

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

This medicine has been authorised under "exceptional circumstances".

This type of authorisation means that due to the rarity of your disease, it has not been possible to obtain complete information about this medicine.

The European Medicines Agency will review annually any new information about the medicine that may become available, and this leaflet will be updated as necessary.

Other sources of information

Further information about this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.

This leaflet is available in all the languages of the European Union/European Economic Area on the website of the European Medicines Agency.

INSTRUCTIONS FOR USE

INCRELEX must be administered using sterile disposable needles and syringes that can be provided by your doctor/pharmacist/nurse. Use small-volume syringes that allow you to extract the prescribed dose with reasonable accuracy.

Preparing the dose

1. Wash your hands before preparing INCRELEX for injection.

1. Use new disposable needles and syringes each time you administer a dose. Do not use the syringes and needles more than once. Dispose of them properly in a sharps container (e.g. a biohazardous waste container), a rigid plastic container (e.g. a detergent bottle), or a metal container (e.g. an empty coffee can). Never share needles and syringes.

1. Check that the liquid is transparent and colourless. Do not use it after the expiry date (which appears on the label after CAD and refers to the last day of the month), or if it is cloudy or contains particles. If a vial freezes, dispose of it properly. Ask your pharmacist how to dispose of unused medicines.

1. If you are using a new vial, remove the protective cap. Do not remove the rubber stopper.

1. Wipe the rubber stopper of the vial with an alcohol-soaked cotton swab to prevent the vial from becoming contaminated with germs that may be introduced when the needle is repeatedly inserted (see Figure 1).

1. Before inserting the needle into the vial, pull the plunger back to introduce an amount of air into the syringe equivalent to the prescribed dose. Insert the needle through the rubber stopper of the vial and push the plunger to inject air into the vial (see Figure 2).

Figure 2:Inject

air into the vial

1. Leave the syringe in the vial and turn both the syringe and the vial over. Hold the syringe and the vial firmly (see Figure 3).

1. Make sure the needle tip is in the liquid (see Figure 4). Pull the plunger to load the correct dose into the syringe (see Figure 5).

1. Before removing the needle from the vial, check if there are air bubbles in the syringe. If there are air bubbles, hold the vial and syringe with the needle straight up and gently tap the syringe until the air bubbles rise. Expel the air bubbles with the plunger and extract liquid again until you get the correct dose (see Figure 6).

Figure 6: Extract the air

bubbles and refill the syringe

1. Remove the needle from the vial and replace the protective cap. Do not let the needle touch anything. You are now ready to inject (see Figure 7).

Figure 7: Ready

to inject

Injecting the dose:

Inject INCRELEX as instructed by your doctor.

Do not administer the injection if you will not be able to eat a little before or after the injection.

1. Choose an injection site, either the arm, thigh, buttock, or abdomen (see below). It is a good idea to change the injection site each time (rotate the injection site).

ArmThighButtockAbdomen

1. Use alcohol or soap and water to clean the skin where you will inject. The injection site must be dry before the injection.

1. Pinch the skin lightly. Insert the needle as instructed by your doctor. Release the skin (see Figure A).

1. Push the plunger slowly until the end, trying to inject all the liquid. Pull the needle straight out and press the injection site gently with a cotton ball or gauze for a few seconds.Do not rub the area(see Figure B).

Figure B: Press (do not

rub) with cotton ball or gauze

1. Follow your doctor's instructions for disposing of the needle and syringe. Do not put the needle back on the syringe. Used needles and syringes must be disposed of properly in a sharps container (e.g. a biohazardous waste container), a rigid plastic container (e.g. a detergent bottle), or a metal container (e.g. an empty coffee can). These containers must be sealed and disposed of properly as instructed by your doctor.