Norditropin nordiflex

Package leaflet: Information for the user

Norditropin NordiFlex, 10 mg/1.5 ml, solution for injection in a pre-filled injector
somatropin
Please read all of this leaflet carefully before using this medicine because it contains
important information for the patient

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet
1. What Norditropin NordiFlex is and what it is used for
2. What you need to know before using Norditropin NordiFlex
3. How to use Norditropin NordiFlex
4. Possible side effects
5. How to store Norditropin NordiFlex
6. Contents of the pack and other information
On the reverse: Instructions for use of the Norditropin NordiFlex injector

1. What Norditropin NordiFlex is and what it is used for

Norditropin NordiFlex contains a biosynthetic human growth hormone called somatropin, which is
identical to the growth hormone produced in the human body. Growth hormone is essential for
normal growth in children and for normal body function in adults.
Norditropin NordiFlex is used to treat growth disorders in children:

• in cases of absent or insufficient growth hormone secretion (growth hormone deficiency);
• in Turner syndrome (a genetic disorder that may affect growth);
• in cases of kidney disorders;
• in cases of short stature and in children born small for gestational age;
• in Noonan syndrome (a genetic disorder that may impair growth).

Norditropin NordiFlex is used as replacement growth hormone in adults:
In adults, Norditropin NordiFlex is used to replace growth hormone when its secretion was insufficient during childhood or when its production has been impaired in adulthood due to a tumour, tumour treatment, or a disease affecting the gland producing growth hormone. Patients who were treated for growth hormone deficiency in childhood should undergo re-evaluation after completion of growth. If growth hormone deficiency is confirmed, treatment should be continued.

2. Important information before using Norditropin NordiFlex

When not to use Norditropin NordiFlex

• if the patient is allergic to somatropin, phenol, or any of the other ingredients of this medicine (listed in section 6);
• after kidney transplantation;
• if there is an active tumour (cancer). Any diagnosed tumours must be inactive, and anti-tumour treatment must have been completed before starting Norditropin NordiFlex;
• in case of acute critical illness, such as open-heart surgery, abdominal surgery, multiple trauma due to an accident, or acute respiratory failure;
• after completion of growth (closure of epiphyses), if there is no growth hormone deficiency.

Warnings and precautions
Before starting treatment with Norditropin NordiFlex, talk to your doctor or pharmacist:

• if the patient has diabetes;
• if the patient has ever had cancer or any other type of tumour;
• in case of recurring headaches, vision disturbances, nausea, or vomiting;
• in case of thyroid gland function disorders;
• during rapid growth, every child may experience worsening of spinal curvature (scoliosis). During treatment with Norditropin NordiFlex, the doctor will check whether the patient (child or adult) shows symptoms of scoliosis;
• if the patient limps or begins to limp during growth hormone treatment, they should inform the doctor;
• if the patient is over 60 years of age or has used somatropin in adulthood for longer than 5 years, due to limited experience;
• in case of kidney disease, kidney function should be monitored by a doctor;
• if the patient is receiving replacement glucocorticosteroid therapy, regular consultations with the doctor are necessary, as the glucocorticosteroid dose may need adjustment;
• Norditropin NordiFlex may cause pancreatitis, which causes severe abdominal and back pain. If abdominal pain occurs in a child or adult after administration of Norditropin NordiFlex, contact a doctor immediately.

Norditropin NordiFlex and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
In particular, inform the doctor if the patient is currently taking or has recently taken any of the following medicines. The doctor may recommend adjusting the dose of Norditropin NordiFlex or other medicines:

• glucocorticosteroids – concomitant use of Norditropin NordiFlex and glucocorticosteroids may affect growth in adults;
• cyclosporine (an immunosuppressive medicine) – dose adjustment may be necessary;
• insulin – dose adjustment may be necessary;
• thyroid hormone – dose adjustment may be necessary;
• gonadotropin (a hormone stimulating the sex glands) – dose adjustment may be necessary;
• anticonvulsants – dose adjustment may be necessary;
• oral estrogens or other sex hormones.

Pregnancy and breastfeeding
Medicines containing somatropin are not recommended for use in women of childbearing age who are not using contraception.

• Pregnancy – If a patient becomes pregnant while using Norditropin NordiFlex, treatment should be discontinued and medical advice sought.
• Breastfeeding – Do not use Norditropin NordiFlex during breastfeeding, as somatropin may pass into breast milk.

Driving and operating machinery
Norditropin NordiFlex has no influence on the ability to drive or operate machinery.

Norditropin contains sodium
Norditropin contains less than 1 mmol of sodium (23 mg) per 1.5 ml, meaning it is essentially "sodium-free".

3. How to use Norditropin NordiFlex

This medicine should always be used exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

Recommended dose
The recommended dose for children depends on body weight and body surface area. The recommended dose for adults depends on height, body weight, gender and sensitivity to growth hormone; the dose should be adjusted until the required dose is achieved.

• Children with growth hormone deficiency or lack of growth hormone: The usual recommended dose is 0.025 to 0.035 mg per kg body weight per day or 0.7 to 1.0 mg per m^2 body surface area per day.
• Children with Turner syndrome: The usual recommended dose is 0.045 to 0.067 mg per kg body weight per day or 1.3 to 2.0 mg per m^2 body surface area per day.
• Children with kidney disease: The usual recommended dose is 0.050 mg per kg body weight per day or 1.4 mg per m^2 body surface area per day.
• Children born small for gestational age: The usual recommended dose is 0.035 mg per kg body weight per day or 1.0 mg per m^2 body surface area per day until target height is reached. (In clinical trials in children born small for gestational age, doses of usually 0.033 and 0.067 mg per kg body weight per day were used.)
• Children with Noonan syndrome: The usual recommended dose is 0.066 mg per kg body weight per day, although your doctor may decide that a dose of 0.033 mg per kg body weight per day is sufficient.
• Adults with growth hormone deficiency or lack of growth hormone: If growth hormone deficiency persists after completion of growth, treatment should continue. The usual starting dose is 0.2 to 0.5 mg per day. The dose should be adjusted until the appropriate dose is established. In adults with growth hormone deficiency, the usual starting dose is 0.1 to 0.3 mg per day. This dose is increased at monthly intervals until the appropriate dose for the individual patient is reached. The maximum daily dose is usually 1.0 mg.

When to use Norditropin NordiFlex
The recommended daily dose should be injected subcutaneously every evening, just before bedtime.

How to use Norditropin NordiFlex
Norditropin NordiFlex contains a solution of growth hormone in a pre-filled, single-use, multidose pen injector with a capacity of 1.5 ml.
Full instructions for using the Norditropin NordiFlex pen injector are provided on the reverse.
Key points from the instructions:

• Check the solution before use by turning the pen upside down once or twice. Do not use the pen if the solution is cloudy or has changed colour.
• Norditropin NordiFlex is intended for use with single-use NovoFine or NovoTwist needles up to 8 mm in length.
• Always use a new needle for each injection.
• Rotate injection sites to avoid skin damage.
• To ensure the full dose is delivered and to avoid injecting air bubbles, always perform a flow check (the so-called “flow test”) before the first injection with a new Norditropin NordiFlex pen.

If a drop of growth hormone solution does not appear at the needle tip, do not use the pen.

• Never share your Norditropin NordiFlex pen with other people.

How long should treatment last

• Children with growth disorders due to Turner syndrome, kidney disease, being born small for gestational age, or Noonan syndrome: treatment should continue until growth is complete, as directed by your doctor.
• Children or adolescents with growth hormone deficiency: treatment should continue into adulthood, as directed by your doctor.

Do not stop using Norditropin NordiFlex without first discussing it with your doctor.

If you use more Norditropin NordiFlex than you should
If you take more somatropin than recommended, contact your doctor immediately.
Prolonged overdosage may cause excessive growth and coarsening of facial features.

If you forget to use Norditropin NordiFlex
Take the next dose at your usual time. Do not use a double dose to make up for a missed dose.

If you stop using Norditropin NordiFlex
Do not stop using Norditropin NordiFlex without first discussing it with your doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions observed in children and adults (frequency unknown):

• rash, wheezing, eyelid, facial or lip swelling, loss of consciousness – these may be symptoms of an allergic reaction;
• headache, vision problems, nausea and vomiting – these may be symptoms of increased intracranial pressure;
• serum thyroxine levels may be decreased;
• hyperglycaemia (elevated blood sugar levels).

If any of the above adverse reactions occur, contact a doctor immediately. Norditropin NordiFlex should be discontinued until the doctor advises continuation of treatment.

During treatment with Norditropin, the development of antibodies against somatropin has been observed rarely.
Increased liver enzyme activity has been reported.
In patients treated with somatropin (the active substance in Norditropin NordiFlex), cases of leukaemia and brain tumour recurrence have been reported; however, there is no evidence of a causal relationship between somatropin and these conditions.
If a patient suspects they have any of the above-mentioned conditions, they should consult their doctor.

Additional adverse reactions in children:
Uncommon (may occur in no more than 1 in 100 children):

• headache,
• redness, itching and pain at the injection site,
• breast enlargement (gynaecomastia).

Rare (may occur in no more than 1 in 1,000 children):

• rash,
• muscle and joint pain,
• swelling of hands and feet due to fluid retention.

In rare cases, children receiving Norditropin NordiFlex may experience knee or hip pain or begin to limp. These symptoms may be due to a condition affecting the upper part of the femur (Legg-Calvé-Perthes disease) or slipping of the femoral epiphysis (juvenile epiphyseal slip), rather than the use of Norditropin NordiFlex.

In clinical studies in children with Turner syndrome, several cases of excessive growth of hands and feet relative to body height have been observed.
A clinical study in children with Turner syndrome has shown that a high dose of Norditropin may possibly increase the risk of ear infections.

If any adverse symptoms worsen or if any adverse reactions not listed in this leaflet occur, inform a doctor or pharmacist, as dose reduction may be necessary.

Additional adverse reactions in adults:
Very common (may occur in more than 1 in 10 adults):

• swelling of hands and feet due to fluid retention.

Common (may occur in no more than 1 in 10 adults):

• headache,
• skin tingling, numbness and pain, mainly in the fingers,
• joint pain and stiffness, muscle pain.

Uncommon (may occur in no more than 1 in 100 adults):

• type 2 diabetes,
• carpal tunnel syndrome, tingling and pain in fingers and hands,
• itching (which may be intense) and injection site pain,
• muscle stiffness,
• breast enlargement (gynaecomastia).

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to gather additional information on the safety of the medicine.

5. How to store Norditropin NordiFlex

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following “Expiry”. The expiry date refers to the last day of the stated month.
Before use, store the Norditropin NordiFlex injection pen in the refrigerator (2°C – 8°C) inside its outer packaging to protect it from light. Do not freeze or expose to high temperatures. Do not store near any cooling elements.
During use, Norditropin NordiFlex 10 mg/1.5 ml may be:

• stored in the refrigerator (2°C – 8°C) for up to 4 weeks or
• stored at room temperature (below 25°C) for up to 3 weeks.

Do not use Norditropin NordiFlex injection pens if they have been frozen or exposed to high temperatures.
Do not use the Norditropin NordiFlex injection pen if the growth hormone solution is cloudy or has changed colour.
The Norditropin NordiFlex injection pen should always be stored without a needle attached.
Always place the cap on the Norditropin NordiFlex injection pen when it is not in use.
Always use a new needle for each injection.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Norditropin NordiFlex contains

• The active substance is somatropin.
• The other ingredients are: mannitol, histidine, poloxamer 188, phenol, water for injections, hydrochloric acid (for pH adjustment) and sodium hydroxide (for pH adjustment).

What Norditropin NordiFlex looks like and contents of the pack
Norditropin NordiFlex is a clear, colourless solution for injection in a single-use, prefilled multidose pen injector with a capacity of 1.5 ml.
1 ml of solution contains 6.7 mg of somatropin.
1 mg of somatropin corresponds to 3 IU of somatropin.
Norditropin NordiFlex is available in the following strengths:
5 mg/1.5 ml (corresponding to 3.3 mg/ml),
10 mg/1.5 ml (corresponding to 6.7 mg/ml).
Pack sizes available: 1 prefilled pen injector, and multipacks containing 5 or 10 prefilled pen injectors. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Finland, Greece, Spain, Ireland, Iceland, Lithuania, Luxembourg, Norway, Poland, Portugal, Romania, Slovakia, Sweden, Hungary, United Kingdom (Northern Ireland), Italy: Norditropin NordiFlex 10 mg/1.5 ml
France: Norditropine NordiFlex 10 mg/1.5 ml

Further information
Detailed information about this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products http://www.urpl.gov.pl.

Norditropin NordiFlex
10 mg/1.5 ml
Instructions for use of the Norditropin NordiFlex pen injector
Before using Norditropin NordiFlex, carefully read the instructions below.

• Norditropin NordiFlex 10 mg/1.5 ml is a single-use, prefilled multidose pen injector containing a solution of human growth hormone.
• The dose selector knob allows setting doses from 0.05 to 3.00 mg in increments of 0.05 mg. The appropriate dose for each patient is determined by the physician.
• Norditropin NordiFlex is intended for use with single-use NovoFine or NovoTwist needles up to 8 mm in length.
• Always begin by checking the name, strength and colour of the Norditropin NordiFlex pen injector to ensure it contains the growth hormone strength appropriate for the patient.
• Use the pen injector only if the growth hormone solution in the cartridge is clear and colourless.
• Always use a new needle for each injection.
• Always check the flow before administering the first injection with a new pen injector – see section 3. Checking the flow.
• Never share your pen injector or needles with other people. This may lead to cross-contamination and transmission of infections.
• Always store the pen injector and needles out of sight and out of reach of children.
• Caregivers must exercise extreme caution when removing and disposing of used needles to reduce the risk of needlestick injury and cross-infection.

Needle (example) Cap Injection device adapter Outer needle shield Inner needle shield Needle Cartridge Paper label Dose window Scale of the injection device Dose window Dose selector knob Dose button
1. Checking the injection device Check the name, strength and colour of the Norditropin NordiFlex injection device to ensure it contains the correct strength of growth hormone. Remove the injection device cap [A]. Check that the solution in the cartridge is clear and colourless by turning the injection device upside down once or twice. Do not use the injection device if the solution in the cartridge is not clear and colourless.	A
2. Attaching the needle Always use a new needle for each injection. This reduces the risk of contamination, infection, leakage of solution, needle blockage and inaccurate dosing. Never use a bent or damaged needle. Peel off the paper label from the needle shield. Screw the needle onto the injection device, holding it straight [B]. Make sure it is securely attached. The needle has two shields; both must be removed:	B
Remove the outer needle shield and keep it for later use to safely remove the needle from the injection device. Remove the inner needle shield by grasping the tab and discard it.
3. Checking the flow Before the first injection using each new injection device, check the flow to ensure proper dosing and to avoid injecting air: Select 0.05 mg [C]. This is one 'click' of the dose selector knob located at the end of the injection device.	C
Holding the injection device with the needle pointing upwards, gently tap the top of the device several times with your finger to allow air bubbles to rise to the upper part [D].	D
While still holding the injection device with the needle pointing upwards, press the dose button fully in [E]. A drop of solution should appear at the tip of the needle. If no drop appears, repeat steps C to E up to 6 times, until a drop appears. If no drop appears, replace the needle and repeat steps C to E once more. If no drop of solution appears, do not use this injection device. Use a new one. Always check the flow before the first injection with a new injection device. Check the flow again if the injection device has been dropped or hit against a hard surface, or if you suspect it is not working properly.	E
4. Setting the dose Check that the dose selector knob is in position 0.0. Set the number of mg prescribed by your doctor [F]. The dose can be increased or decreased by turning the dose selector knob in opposite directions. When turning the dose selector knob backwards, be careful not to press the dose button, as this may cause leakage of solution. You cannot set a dose higher than the number of mg remaining in the injection device.	F
5. Administering the injection Follow your doctor’s or nurse’s instructions when administering the injection. Change injection sites to avoid skin damage. Insert the needle under the skin. Administer the dose by pressing the dose button fully in. Only press the dose button during injection [G]. While keeping the dose button fully pressed, leave the needle under the skin for at least 6 seconds. This ensures the full dose is delivered.	G
6. Removing the needle Carefully place the outer needle shield back onto the needle without touching the needle. Unscrew the needle and dispose of it carefully according to your doctor’s or nurse’s instructions [H]. Never re-cap the needle with the inner needle shield as you may accidentally prick yourself. After each use, replace the cap on the injection device. After each injection, always remove and dispose of the needle, and store the injection device without a needle attached. This reduces the risk of contamination, infection, leakage of solution, needle blockage and inaccurate dosing. When the injection device is empty, dispose of it without the needle attached, according to instructions provided by your doctor, nurse or local regulations. Caregivers must exercise extreme caution when removing and disposing of used needles to reduce the risk of needlestick injury and cross-infection.	H
7. Handling the injection device Handle the Norditropin NordiFlex injection device with care. Do not drop the injection device or hit it against hard surfaces. If the injection device has been dropped or if you suspect it may not be working properly, always attach a new needle and check the solution flow before administering an injection. Do not refill the injection device – it is a pre-filled semi-automatic injection device. Do not attempt to repair or disassemble the injection device. Protect the injection device from dust, dirt, frost and direct sunlight. Do not attempt to wash, soak or lubricate the injection device. If necessary, clean it with a cloth dampened with a mild detergent. Do not freeze the injection device and do not store it near any cooling element, such as the wall of a refrigerator.

• For information on storage of the injector, see section 5. How to store Norditropin NordiFlex, on the reverse side of this leaflet.