Skytrofa

Package leaflet: Information for the user

Skytrofa 3 mg, powder and solvent for injectable solution in cartridge, 3.6 mg, powder and solvent for injectable solution in cartridge, 4.3 mg, powder and solvent for injectable solution in cartridge, 5.2 mg, powder and solvent for injectable solution in cartridge, 6.3 mg, powder and solvent for injectable solution in cartridge, 7.6 mg, powder and solvent for injectable solution in cartridge, 9.1 mg, powder and solvent for injectable solution in cartridge, 11 mg, powder and solvent for injectable solution in cartridge, 13.3 mg, powder and solvent for injectable solution in cartridge

lonapegsomatropin
This medicinal product is subject to additional monitoring. This will allow rapid identification of
new safety information. You can help by reporting any side effects you experience while taking
this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine for yourself or your child,
as it contains important information for you or your child.
• 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 other people, even if they have
the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or
pharmacist. See section 4.
Contents of this leaflet

1. What Skytrofa is and what it is used for
2. What you or your child should know before using Skytrofa
3. How to use Skytrofa
4. Possible side effects
5. How to store Skytrofa
6. Contents of the pack and other information

1. What Skytrofa is and what it is used for

Skytrofa is a medicine that contains the active substance lonapegsomatropin. This substance can
be converted by the body into somatropin, also known as human growth hormone (hGH).
Somatropin is necessary for the growth of bones and muscles and helps the body to develop the correct
amount of fat and muscle tissue.
Skytrofa is used to treat children and adolescents aged between 3 and 18 years who have not grown adequately because their body does not produce, or does not produce enough, growth hormone.
Doctors call this condition growth hormone deficiency (GHD). After injection, Skytrofa is slowly converted into somatropin, which provides the missing growth hormone.

2. What you or your child should know before using Skytrofa

Do not use Skytrofa

• if you are allergic to lonapegsomatropin or to any of the other ingredients of this medicine (listed in section 6)
• if you have a growing tumour (cancer). Before starting treatment with Skytrofa, you must have completed your anti-tumour treatment and the tumours must be inactive
• if you have recently undergone open-heart surgery or abdominal surgery, have suffered multiple accidental trauma, or have experienced acute respiratory failure
• if your doctor has told you that the growing parts of the bones responsible for height increase (growth plates or epiphyses) have closed and stopped growing

If any of these situations apply to you, inform your doctor before starting treatment.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Skytrofa. It is very important to inform them about the following:

• if you have previously had an intracranial tumour, a doctor will examine you regularly during treatment to monitor for possible recurrence of the tumour or of any other cancer;
• if you develop severe headache, blurred vision, vomiting, or inability to coordinate voluntary muscle movements (ataxia), especially during the first weeks of treatment, inform your doctor immediately. These could be signs of increased pressure in the skull (intracranial pressure). See section 4, possible side effects;
• if you have diabetes mellitus, high blood sugar levels (glucose intolerance), or additional risk factors for diabetes, you may need periodic blood glucose monitoring and possibly adjustment of your diabetes medication;
• if you are receiving treatment with corticosteroids for renal insufficiency, consult your doctor, as periodic adjustment of steroid dosage may be necessary;
• if you are receiving treatment with thyroid hormones or are about to start thyroid hormone replacement therapy, your doctor will periodically test your thyroid function and may need to adjust your dose;
• if, while walking, you experience persistent pain in the hip or knee or start limping during treatment with somatotropin hormone, inform your doctor. These could be symptoms of a disorder affecting the thigh bone (femur) where it connects to the hip (epiphysiolysis or femoral head slippage), which occurs more frequently in children treated with somatotropin hormone. These symptoms could also be caused by loss of bone tissue due to inadequate blood supply (osteonecrosis), which has been reported in patients treated with other growth hormone products. Consult your doctor if you experience persistent pain in any joint;
• if you notice a lateral curvature of your spine (scoliosis), you should be examined frequently by your doctor;
• if you experience worsening stomach pain (abdominal pain), inform your doctor. Your doctor may test you for pancreatitis, which is inflammation of an organ called the pancreas. See section 4, possible side effects;
• if you experience signs and symptoms of a severe, sudden allergic reaction (e.g. difficulty breathing, swelling of the face, mouth, or tongue, rapid heartbeat, hives, rash, fever), seek medical attention immediately;
• if you have Prader-Willi syndrome, you should not receive treatment with Skytrofa unless you also have somatotropin hormone deficiency. Skytrofa has not been studied in individuals with Prader-Willi syndrome, therefore its efficacy as a treatment for this disorder is unknown;
• a small number of patients who have received somatotropin hormone replacement have developed a type of blood and bone marrow cancer (leukemia). However, it has not been proven that somatotropin hormone treatment causes cancer;
• if you have experienced immediate complications after open-heart surgery or abdominal surgery, a severe accident (trauma), or an acute critical illness such as acute respiratory failure;
• if you are a patient taking oral contraceptives or estrogen hormone replacement therapy, you may need an increased dose of Skytrofa. If you or your child stop taking oral estrogens, the dose of Skytrofa may need to be reduced.

Other medicines and Skytrofa

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

In particular, inform your doctor if you are taking or have recently taken any of the following medicines:

• insulin or any other medicine for treating diabetes mellitus
• treatments with thyroid hormones such as levothyroxine
• tablets containing estrogens, including tablets for hormone replacement therapy or contraception
• steroids or synthetic adrenal hormones (corticosteroids or glucocorticoids)
• medicines for treating epilepsy or seizures (seizure episodes) – antiseizure medicines (anticonvulsants) such as carbamazepine
• cyclosporine (an immunosuppressive medicine) – a medicine to suppress the immune system
• theophylline, a medicine used to treat asthma and other chronic lung diseases

Your doctor may need to adjust the dose of these medicines or the dose of Skytrofa.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

If you are able to have children, you must not use Skytrofa unless you are also using reliable contraception. Data on the use of Skytrofa in pregnant women are not available.
Skytrofa must not be used during pregnancy. This is because it is unknown whether it could harm the unborn child. If you are pregnant, suspect you are pregnant, or are planning a pregnancy, inform your doctor. If you become pregnant during treatment, inform your doctor immediately.

Breastfeeding

It is not known whether Skytrofa passes into breast milk. However, since lonapegsomatropin is not absorbed orally, it is unlikely to cause adverse effects in the breastfed infant. If you are breastfeeding or intend to breastfeed, consult your doctor about the use of Skytrofa. Skytrofa may be used during breastfeeding only under strict medical indication.

Driving and using machines

Skytrofa does not impair the ability to drive vehicles or operate machinery.

3. How to use Skytrofa

This medicine will only be prescribed by a doctor experienced in treatment with somatotropic hormone and who has confirmed the diagnosis.
Always use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor. Your doctor will show you how to use Skytrofa.
Skytrofa is administered as an injection under the skin (subcutaneous injection). This means it is injected using a short needle into the fatty tissue beneath the skin of the abdomen, buttock, or thigh. It is important to change the injection site each week to avoid damaging the skin. At the beginning of treatment, your doctor or nurse will inform you of the correct dose and show you how to administer the injection.

Recommended dose
Your doctor will determine the dose of Skytrofa based on body weight in kilograms. Since lonapegsomatropin is converted into somatropin in the body, Skytrofa doses are expressed according to the amount of somatropin they produce. The recommended dose of Skytrofa is 0.24 mg of somatropin per kilogram of body weight, administered once weekly.
If switching from daily somatropin therapy to once-weekly Skytrofa, your doctor will instruct you to wait at least 8 hours between the final daily dose of somatropin and the first dose of Skytrofa. The recommended dose may be reduced based on the previous daily dose of somatropin.

When to use Skytrofa
You should receive a Skytrofa injection once a week, on the same day each week, at any time of day.
If necessary, you may change the weekly injection day. Skytrofa may be administered up to 2 days before or 2 days after the scheduled day. At least 5 days must pass between the last injection on the regular day and the first dose on the new scheduled day. Once you have chosen a new administration day, continue to give the injection on that day every week. If you have any doubts about how to proceed, consult your doctor.

Preparation and administration
Before using the medicine, read the “Instructions for Use” at the end of this leaflet.
Skytrofa is supplied in a dual-chamber cartridge containing both the medicine (powder) and solvent (liquid). It must be used with the needles provided. For injections, you will also need the Skytrofa Auto-Injector. The Skytrofa Auto-Injector is supplied separately.
The powder and solvent will be mixed into an injectable solution by the Skytrofa Auto-Injector. After mixing, the solution is ready for use, and the medicine can be injected under the skin using the Skytrofa Auto-Injector.
Read the instructions for use provided with the Skytrofa Auto-Injector.

If you or your child uses more Skytrofa than you should
If you have used more Skytrofa than intended for the injections, seek advice from your doctor. If the injections contain too much Skytrofa, blood sugar levels may drop too low and later become too high. Long-term overdose may cause abnormal growth.

If you or your child forgets to use Skytrofa
If you miss the weekly dose or are 1 or 2 days late: administer the injection today, then continue on your usual day the following week. If you are 3 or more days late: skip the missed dose and resume injections on your next scheduled dosing day. Maintain an interval of at least 5 days between injections.

If you or your child stops using Skytrofa
Do not stop using Skytrofa without consulting your doctor. If you stop taking Skytrofa too early, growth rate may decrease and final height may be lower than what could be achieved by completing the full course of treatment.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common side effects (may affect more than 1 in 10 people)

• Headache

Common side effects (may affect up to 1 in 10 people)

• Low levels of the hormone thyroxine observed in blood tests (secondary hypothyroidism)
• Joint pain (arthralgia)
• Reactions at the injection site. The skin around the injection area may become uneven or lumpy, but this should not occur if the injection is administered each time at a different site.

Uncommon side effects (may affect up to 1 in 100 people)

• Sudden severe allergic reaction, including angioedema (rapid swelling of the mucous membranes or skin, which may occur in the face, mouth, tongue, abdomen, arms, and legs)
• Reduced levels of the hormone cortisol observed in blood tests
• Joint stiffness (arthritis)
• Increased lateral curvature of the spine (scoliosis)
• Growing pains
• Breast enlargement in males

Frequency not known (cannot be estimated from the available data)
The following side effects have been observed with other medicines containing somatropin hormone.

• Leukemia
• Type 2 diabetes mellitus
• Increased pressure of the fluid surrounding the brain (causing symptoms such as severe headache, visual disturbances, and vomiting)
• Numbness/tingling
• Muscle pain
• Swelling of the lower legs and feet and/or arms and hands
• Facial swelling
• Skin rash
• Itching sensation
• Hives (urticaria)

If any side effect worsens, inform your doctor or pharmacist.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in the . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Skytrofa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep the medicine in its original packaging to protect it from light.
Skytrofa may be removed from the refrigerator and stored at temperatures up to 30 °C for a maximum period of 6 months. During these 6 months, the medicine may be refrigerated again (2 °C – 8 °C). Record on the carton the date when Skytrofa was first removed from the refrigerator.

Discard the medicine 6 months after the date it was first stored outside the refrigerator.
The powder is white to off-white in colour and the solvent is a colourless, clear solution.
The mixed solution is colourless and clear. The solution may sometimes contain air bubbles. This is normal. Do not use this medicine if you see visible particles in the mixed solution.
Administer the injection immediately after mixing the powder and solvent using the Skytrofa Auto-Injector. If the mixed solution cannot be used immediately, it must be used within 4 hours.
When a cartridge with needle has been used, dispose of it carefully in a suitable container.
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 Skytrofa contains
The active substance is lonapegsomatropin.
Cartridges are available in 9 dosage levels:

Skytrofa 3 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 3 mg of somatropin (equivalent to 8.6 mg of
lonapegsomatropin [powder]) and 0.279 mL of solvent (liquid). After mixing, the
concentration of somatropin is 11 mg/mL.

Skytrofa 3.6 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 3.6 mg of somatropin (equivalent to 10.3 mg of
lonapegsomatropin [powder]) and 0.329 mL of solvent (liquid). After mixing, the
concentration of somatropin is 11 mg/mL.

Skytrofa 4.3 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 4.3 mg of somatropin (equivalent to 12.3 mg of
lonapegsomatropin [powder]) and 0.388 mL of solvent (liquid). After mixing, the
concentration of somatropin is 11 mg/mL.

Skytrofa 5.2 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 5.2 mg of somatropin (equivalent to 14.8 mg of
lonapegsomatropin [powder]) and 0.464 mL of solvent (liquid). After mixing, the
concentration of somatropin is 11 mg/mL.

Skytrofa 6.3 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 6.3 mg of somatropin (equivalent to 18 mg of
lonapegsomatropin [powder]) and 0.285 mL of solvent (liquid). After mixing, the
concentration of somatropin is 22 mg/mL.

Skytrofa 7.6 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 7.6 mg of somatropin (equivalent to 21.7 mg of
lonapegsomatropin [powder]) and 0.338 mL of solvent (liquid). After mixing, the
concentration of somatropin is 22 mg/mL.

Skytrofa 9.1 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 9.1 mg of somatropin (equivalent to 25.9 mg of
lonapegsomatropin [powder]) and 0.4 mL of solvent (liquid). After mixing, the
concentration of somatropin is 22 mg/mL.

Skytrofa 11 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 11 mg of somatropin (equivalent to 31.4 mg of
lonapegsomatropin [powder]) and 0.479 mL of solvent (liquid). After mixing, the
concentration of somatropin is 22 mg/mL.

Skytrofa 13.3 mg, powder and solvent for injectable solution (injection) in cartridge
Each dual-chamber cartridge contains 13.3 mg of somatropin (equivalent to 37.9 mg of
lonapegsomatropin [powder]) and 0.574 mL of solvent (liquid). After mixing, the
concentration of somatropin is 22 mg/mL.

- Other components of this medicinal product (for all dosage strengths) are:
Powder: succinic acid, trehalose dihydrate, tromethamine
Solvent: water for injections

Description of the appearance of Skytrofa and contents of the package
Skytrofa contains the medicinal product as a powder together with a solvent to prepare an injectable
solution, within a dual-chamber cartridge, with the powder in one chamber and the solvent in the other.
The powder is white to ivory white in color, and the solvent is a colorless, clear solution. Once the
powder and solvent have been mixed into an injectable solution, the resulting solution is colorless and
clear.

Each package of Skytrofa contains 4 single-use dual-chamber cartridges, individually packaged in
blister packs, and 6 disposable injection needles (including two spare needles). Each cartridge is equipped
with a specific label featuring dual-color coding ribbons used exclusively by the Skytrofa Auto-Injector
to select the appropriate mixing settings. The colors corresponding to the dosages are indicated on the
package box and the blister foil and must be used to distinguish individual dosage strengths.

The colors corresponding to the dosages on the box and blister indicate the dosage strength of your Skytrofa medicine:

Skytrofa is designed for use with the provided injection needles and with the Skytrofa Auto-Injector.
The Skytrofa Auto-Injector is not included in the pack and is supplied separately. Instructions for
use of the Skytrofa Auto-Injector are provided in the package leaflet of that device.
Marketing Authorization Holder
Ascendis Pharma Endocrinology Division A/S
Tuborg Boulevard 12
DK-2900 Hellerup
Denmark
Manufacturer
Ascendis Pharma A/S
Tuborg Boulevard 12
DK-2900 Hellerup
Denmark
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu .

Instructions for use

This guide is designed to help you prepare, mix, and administer the injection of the medicine
Skytrofa.
These instructions are divided into 5 steps:
Introduction to the components of your or your child’s medicine
Preparation of your or your child’s medicine
Mixing your or your child’s medicine
Injection of your or your child’s medicine
After the injection of your or your child’s medicine
If at any time you or your child needs help, contact your doctor, pharmacist, or nurse.

What you should know before starting

• Always read the package leaflet before use.
• Always wash and dry your hands.
• A new cartridge must be used for each injection.
• A new needle must be used for each injection. Do not reuse the needle.
• Do not use this medicine after the expiry date printed after “Exp./EXP” on the outer carton and on the cartridge packaging, or 6 months after the date it was first removed from refrigeration (whichever occurs first).
• Do not use this medicine if you notice visible particles in it.
• The cartridge and needle are single-use and are designed to be used only with the Skytrofa Auto-Injector (referred to below as “auto-injector”).

Introduction to the components of your or your child’s medicine
Skytrofa consists of a powder and a solvent for injectable solution contained in a cartridge. Each
package contains 4 single-use cartridges and 6 disposable injection needles. The cartridge contains the
medicinal powder and the solvent used to mix the powder.

Dual-chamber cartridge
Solvent
Powder
Injection needle
For injections, you will also need the Skytrofa Auto-Injector. This device is not included in the
Skytrofa package and is supplied in a separate package. Also read the instructions for use provided with the Skytrofa Auto-Injector.

Preparation of your or your child’s medicine
If you are storing the medicine in the refrigerator, remove it 15 minutes before use.

1. Cartridge and needle inspection and assembly

• Remove the cartridge packaging.
• Check the expiration date and dosage on the cartridge packaging.
• Do not use if the expiration date printed after "EXP" has been exceeded.

Expiration date  Dosage

• Open the cartridge packaging up to the red STOP mark. This way, the orange connector will remain in the cartridge packaging. An orange connector is applied to the cartridge inside the blister to secure the cartridge stopper in place during transport. Leave this part in place.

• Lift the cartridge and remove it from the packaging.

• If an orange connector is still attached to the cartridge, remove it by pulling it straight off, and discard it.

• Remove a new needle. If the protective seal is not fully intact or appears damaged, do not use.
• Remove the protective paper cover.

2. Turning on the auto-injector

• To turn on the auto-injector, press and release the green button.

• You will hear 2 loud beeps, the battery icon will light up, and the

green upper part will start to
flash.

3. Inserting the cartridge

• Insert the cartridge into the flashing green top part.

• Press down on the cartridge with one finger until it clicks into place. The green top stops

flashing, the green mixing
icon lights up, and the battery
icon turns off.

Mixing of your or your child's medicine

4. Waiting during mixing

Wait
for

• Wait 4 to 8 minutes for the autoinjector to mix the medicine.
• Observe the gradual illumination of the progress bar.
• Wait until you hear 2 strong acoustic signals and the entire progress bar starts flashing.

5. Rotating the auto-injector upward and downward

• Rotate the auto-injector upward and downward. A clicking sound confirms correct rotation.
• Rotate 5 to 10 times until you hear 2 loud audible signals and the progress bar, except for the top element, lights up.

6. Completion of mixing

Injection of the medicine for you or your child

7. Control of the mixed solution

• The solution has been mixed correctly if it is colorless and clear (the presence of air bubbles is acceptable). OK
• Do not use the solution if visible particles are present. If visible particles are present, press the green button for 3 seconds and remove the cartridge.

8. Preparation for injection

Front Back

• Choose the injection site: stomach, thighs, or buttocks. Rotate the injection site each week.

Stomach
Buttocks
(abdomen)
Thighs

9. Injection of the medicinal product

After the injection of the medicine for you or your child

10. Removing the cartridge

• Press the needle cap onto the flashing green upper part.

• Press the needle cap downward to release the cartridge.

• Remove the used cartridge.

11. Disposal of cartridge and needle

Does the weekly dose require 2 cartridges?

• Perform the second injection by repeating steps 1 to 11 using a new cartridge and a new needle.

12. Storage of the auto-injector