CRYSVITA 10 mg Injectable Solution in Pre-filled Syringe

Introduction

Package Leaflet: Information for the User

CRYSVITA 10mg solution for injection in pre-filled syringe

CRYSVITA 20mg solution for injection in pre-filled syringe

CRYSVITA 30mg solution for injection in pre-filled syringe

burosumab

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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is CRYSVITA and what is it used for
2. What you need to know before you use CRYSVITA
3. How to use CRYSVITA
4. Possible side effects
5. Storage of CRYSVITA
6. Contents of the pack and other information

1. What is CRYSVITA and what is it used for

What is CRYSVITA

CRYSVITA contains the active substance burosumab. It is a type of medicine called a human monoclonal antibody.

What is CRYSVITA used for

CRYSVITA is used to treat X-linked hypophosphataemia (XLH). It is used in children and adolescents from 1 to 17 years of age and in adults.

CRYSVITA is used to treat tumour-induced osteomalacia (TIO) when the tumour that causes it cannot be removed or found, in children and adolescents from 1 to 17 years of age and in adults.

What is X-linked hypophosphataemia (XLH)

X-linked hypophosphataemia is a genetic disease.

• People with XLH have higher levels of a hormone called fibroblast growth factor 23 (FGF23).
• FGF23 reduces the amount of phosphate in the blood.
• Low phosphate levels can:

• cause bones not to harden properly and, in children and adolescents, not to grow properly;
• cause pain and stiffness in bones and joints.

What is tumour-induced osteomalacia (TIO)

• People with TIO have higher levels of a hormone called FGF23 produced by certain types of tumours.
• FGF23 reduces the amount of phosphate in the blood.
• Low phosphate levels can cause softening of the bones, muscle weakness, tiredness, bone pain, and fractures.

How CRYSVITA works

CRYSVITA binds to FGF23 in the blood, preventing FGF23 from working and increasing phosphate levels in the blood to normal levels.

2. What you need to know before you use CRYSVITA

Do not use CRYSVITA

• if you are allergic to burosumab or any of the other ingredients of this medicine (listed in section 6);
• if you are taking phosphate supplements or certain vitamin D supplements (which contain the so-called active vitamin D [e.g. calcitriol]);
• if you already have high phosphate levels in your blood (hyperphosphataemia);
• if you have severe kidney disease or kidney failure.

Allergic reactions

Stop using CRYSVITA and contact your doctor immediately if you get any of the following side effects, as they could be signs of an allergic reaction:

• rash and itching all over your body;
• severe swelling of your eyelids, mouth, or lips (angioedema);
• shortness of breath;
• fast heartbeat;
• sweating.

Do not use CRYSVITA if any of the above applies to you. If you are unsure, consult your doctor before using CRYSVITA.

Warnings and precautions

Skin reactions

You may get skin reactions at the injection site, see section 4 for more information. If these reactions are severe, tell your doctor.

Tests and checks

Your doctor will check your phosphate and calcium levels in your blood and urine and may also do a kidney ultrasound during treatment to reduce the risk of hyperphosphataemia (too much phosphate in the blood) and ectopic mineralization (calcium build-up in tissues such as the kidneys). Your doctor will also check your parathyroid hormone level in your blood from time to time.

Children under 1 year

CRYSVITA should not be given to children under 1 year of age, as its safety and effects in this age group have not been studied.

Other medicines and CRYSVITA

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

Do not use CRYSVITA and tell your doctor if you are taking:

• phosphate supplements;
• certain vitamin D supplements (which contain the so-called active vitamin D [e.g. calcitriol]). There are some vitamin D supplements that you can continue to use or start using, and your doctor will tell you which ones.

Consult your doctor before using CRYSVITA:

• if you are taking medicines that work in the same way as calcium (calcimimetics). If used together, they may lower your calcium levels;
• if you are a TIO patient and are about to receive treatment for the underlying tumour (i.e. radiotherapy or surgical removal). In this case, CRYSVITA treatment will not be started until after tumour treatment and if serum phosphate levels are low.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine. This is because it is not known whether CRYSVITA will affect your baby.

CRYSVITA should not be used during pregnancy.

If you can become pregnant, you must use an effective method of contraception while using CRYSVITA and for at least 14 weeks after the last dose. You should discuss this with your doctor.

It is not known whether CRYSVITA passes into breast milk, and it cannot be excluded that it may affect newborns/infants. You should discuss this with your doctor.

Driving, cycling, and using machines

CRYSVITA may cause dizziness and affect your ability to cycle, use tools, or machines, or drive. If you feel affected, do not cycle, do not use tools or machines, and do not drive. Tell your doctor.

CRYSVITA contains sorbitol

CRYSVITA 10 mg solution for injection in pre-filled syringe: this medicine contains 15.30 mg of sorbitol in each pre-filled syringe.

CRYSVITA 20 mg solution for injection in pre-filled syringe: this medicine contains 30.61 mg of sorbitol in each pre-filled syringe.

CRYSVITA 30 mg solution for injection in pre-filled syringe: this medicine contains 45.91 mg of sorbitol in each pre-filled syringe.

3. How to use CRYSVITA

CRYSVITA should be given by injection under the skin (subcutaneously) in the upper arm, abdomen, buttock, or thigh. This medicine can be given to you by a healthcare professional or, alternatively, your doctor may recommend that you or a caregiver give the injection of CRYSVITA. If they suggest that you give it to yourself, a healthcare professional will provide training to show you or your caregiver how to use CRYSVITA correctly before the first self-injection.

The first self-injection after starting treatment or after any dose change should be given in front of a healthcare professional. At the end of this leaflet, there is a detailed section of "Instructions for use" for the pre-filled syringe. Always follow these instructions carefully when giving the injection of CRYSVITA to yourself or your child.

Follow the instructions for administration of this medicine given by your doctor, nurse, or pharmacist. If you are unsure, consult your doctor, nurse, or pharmacist again.

How much CRYSVITA you will need

The dose is determined based on your body weight. Your doctor will calculate the correct dose for you.

Dose for XLH and TIO

You will need to have your dose of CRYSVITA injected:

• every 2 weeks in children and adolescents from 1 to 17 years of age;
• every 4 weeks in adults.

Your doctor will do checks to make sure you are getting the correct dose and may change the dose or how often you have injections if needed.

Maximum dose for patients with XLH

The maximum dose you will get for the treatment of XLH is 90 mg.

Maximum dose for patients with TIO

The maximum dose you will get for the treatment of TIO:

• for children from 1 to 12 years of age is 90 mg;
• for adolescents from 13 to 17 years of age and for adults is 180 mg.

Patients with TIO

If you are a TIO patient who needs treatment for the underlying tumour (i.e. radiotherapy or surgical removal), your doctor will stop CRYSVITA treatment. Once tumour treatment is finished, your doctor will check your phosphate levels and restart CRYSVITA treatment if your serum phosphate levels are low.

If you are given too much CRYSVITA

If you think you have been given too much CRYSVITA, tell your doctor immediately.

If you miss a dose of CRYSVITA

If you miss a dose, consult your doctor immediately. The missed dose should be given as soon as possible, and your doctor will reschedule your future doses as needed.

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

4. Possible side effects

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

Side effects in children and adolescents with XLH

Very common (may affect more than 1 in 10 children and adolescents)

• dental abscess (infection)
• cough
• headache
• dizziness
• vomiting
• nausea
• diarrhoea
• constipation
• dental caries
• rash
• muscle pain (myalgia) and pain in hands and feet
• reactions at the injection site, which can include:

• redness or rash
• pain or itching
• swelling
• bleeding or bruising

These reactions at the injection site are usually mild and occur within 1 day of the injection and usually improve within 1 to 3 days.

• fever
• low vitamin D levels in the blood

Frequency not known (cannot be estimated from the available data)

• high phosphate levels in the blood

Side effects in children and adolescents with TIO

Side effects in children and adolescents are not known, as no clinical studies have been done.

Side effects in adults with XLH and TIO

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

• dental abscess (infection)
• headache
• dizziness
• restless legs syndrome (an irresistible urge to move your legs to stop uncomfortable, painful, or strange feelings in your legs, especially before sleeping or during the night)
• constipation
• back pain
• muscle spasms
• reactions at the injection site, which can include pain or swelling
• low vitamin D levels in the blood

Common (may affect up to 1 in 10 adults)

• rash
• high phosphate levels in the blood

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of CRYSVITA

Keep CRYSVITA out of the sight and reach of children.

Do not use CRYSVITA after the expiry date which is stated on the carton and label after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Keep the pre-filled syringe in the outer carton to protect it from light.

Do not use CRYSVITA if it contains visible particles.

Medicines should not be disposed of via wastewater or household waste. This will help protect the environment.

If you are self-injecting, see step 4 of the "Instructions for use" at the end of this leaflet for disposal of unused medicines and materials. If you are unsure about how to dispose of medicines that are no longer needed, ask your healthcare professional or pharmacist.

6. Container Contents and Additional Information

Composition of CRYSVITA

The active ingredient is burosumab.

Pre-filled syringe of 10 mg:

Each pre-filled syringe contains 10 mg of burosumab in 0.33 ml of solution.

Pre-filled syringe of 20 mg:

Each pre-filled syringe contains 20 mg of burosumab in 0.67 ml of solution.

Pre-filled syringe of 30 mg:

Each pre-filled syringe contains 30 mg of burosumab in 1 ml of solution.

The other components are L-histidine, D-sorbitol (E 420), polysorbate 80, L-methionine, 10% hydrochloric acid, and water for injectable preparations. (See "CRYSVITA contains sorbitol" in section 2 for more information)

Appearance and Container Contents of the Product

CRYSVITA is presented as a clear to slightly opalescent and colorless to pale brown-yellow injectable solution in a pre-filled syringe. Each container contains 1 pre-filled syringe.

The different concentrations of the medication can be identified by a plunger rod of a different color: 10 mg (blue), 20 mg (red), and 30 mg (green).

Marketing Authorization Holder

Kyowa Kirin Holdings B.V.

Bloemlaan 2

2132NP Hoofddorp

Netherlands

[email protected]

Manufacturer

allphamed PHARBIL Arzneimittel GmbH

Hildebrandstr. 10-12

37081 Göttingen

Germany

Kyowa Kirin Holdings B.V.

Bloemlaan 2

2132NP Hoofddorp

Netherlands

Date of Last Revision of this Leaflet:June 2025

Other Sources of Information

Detailed information on this medication is available on the European Medicines Agency website: https://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

INSTRUCTIONS FOR USE

The following instructions for use are intended for:

• self-administration;

• administration by a caregiver or healthcare professional.

Read these instructions for use carefully before using CRYSVITA:

• This medication should only be administered to yourself or another person if it has been prescribed by your doctor.
• This medication should only be administered to yourself or another person after receiving training on the injection technique. The first self-injection after starting treatment or after any dose change should be performed in front of a doctor, pharmacist, or nurse (healthcare professional).
• Follow exactly the administration instructions for this medication as indicated by your healthcare professional. If in doubt, consult your healthcare professional again.
• Your doctor will prescribe the correct dose. Your dose is measured in milligrams (mg).
• Your healthcare professional will tell you how much CRYSVITA to administer to yourself or another person. You may need more than one pre-filled syringe to get the correct dose.
• If your healthcare professional tells you that more than one injection is needed to administer the required dose, you must repeat steps 2 to 4 for each injection.
• Use new materials for each injection.
• Each pre-filled syringe is for single use only. Always use a new pre-filled syringe of CRYSVITA for each injection; see step 4 on how to dispose of used syringes and other materials.
• Whenever possible, use a different body area for each injection.
• When administering CRYSVITA to a small child, it may be helpful to have another person present to calm them.
• Do not use CRYSVITA if you are allergic to any of the components of this medication. Stop using CRYSVITA if you have any allergic reaction during or after the injection and contact your healthcare professional immediately. See section 2 of the leaflet for more information.

CRYSVITA is available in pre-filled syringes of three different concentrations: 10 mg (blue), 20 mg (red), and 30 mg (green). The amount of liquid in the pre-filled syringes varies depending on the concentration. The syringes you are given will depend on the dose you have been prescribed.

These instructions are used for the three concentrations.

The following are the parts of the CRYSVITA pre-filled syringe:

Step 1. Gather and Inspect the Materials

CRYSVITA should be stored in the refrigerator before use. When you need to administer CRYSVITA to yourself or another person, take CRYSVITA out of the refrigerator, but keep it in the box. Place the box on a clean and flat surface.

Check the concentration of each pre-filled syringe you have been given in the CRYSVITA boxes.

Make sure you have the correct number of syringes and the correct concentrations of each pre-filled syringe to match the dose in mg advised by your healthcare professional.

If you are unsure, ask your healthcare professional.

Let the pre-filled syringe box reach room temperature for 45 minutes.Do notheat the pre-filled syringe in any other way, such as with hot water or in a microwave. Do notexpose the pre-filled syringe to direct sunlight.

After 45 minutes, open the box and remove the plastic tray. Hold the pre-filled syringe gently by the cylinder and take it out of the tray.

Do notlift the syringe by the plunger rod or the needle cap.

Do nottouch the plunger rod or remove the needle cap until you are ready to use it.

Do notuse the pre-filled syringe if the needle cap is missing or not properly placed.

Do notuse the pre-filled syringe if it is cracked or broken.

Check the concentration on the label of each pre-filled syringe.

Check the expiration date (indicated after EXP) on the label of each pre-filled syringe.

Do notuse the pre-filled syringe if it has passed the expiration date.

Inspect the liquid in the pre-filled syringe. Do not shake.

The CRYSVITA liquid should be clear to slightly opalescent and colorless to pale brown-yellow.

Note:It is normal for the medication to contain air bubbles. Air bubbles will not harm you or affect your dose.

Do notuse the pre-filled syringe if the liquid has changed color, is cloudy, or contains particles.

Wash your hands well with water and soap before proceeding to step 2.

Step 2. Prepare the Injection Site

If you are going to administer more than one injection, use a different sitefor each injection. Clean each injection site with a new alcohol wipe and let the skin dry.

CRYSVITA should be injected into clean and dry skin.

Step 3. Administer the CRYSVITA Injection

• Do nottouch the needle or the plunger rod.
• Do notallow the needle to come into contact with any surface once the cap is removed.
• Do notuse the syringe if it falls after removing the cap or if the needle appears to be damaged.

Hold the syringe between your thumb and index finger of your dominant hand.

The needle should be inserted into the skin at a 45-degree or 90-degree angle.

Your healthcare professional will tell you which angle to use.

Use a quick motion like a dart to insert the needle into the pinched skin.

Do notpush the plunger when inserting the needle.

When you have administered the complete dose, keep the syringe at the same injection angleand remove it by gently pulling it outward.

Do nottilt the syringe while removing it.

Do notrub the injection site.

Release the pinched skin

If some blood appears, press the injection site with a cotton ball or gauze for a few seconds.

Step 4. After Each Injection

Place the caps and used syringes in the sharps container.

Do notthrow the syringes in the trash.

When your sharps container is almost full, you will need to follow local guidelines to request another container and dispose of it properly.

Reminder:If you are going to administer more than one injection, repeat steps 2 to 4 for each one.

Use new materials for each injection.

Record the injection date and all the areas where you have injected so that, if possible, you can use different areas for the next injection