Product Information for the User

CRYSVITA 10 mg injectable solution

CRYSVITA 20 mg injectable solution

CRYSVITA 30 mg injectable solution

burosumab

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

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this product information. See section 4.

What is CRYSVITA

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

How is CRYSVITA used

CRYSVITA is used to treat hypophosphatemia associated with X-linked hypophosphatemia (XLH). It is used in children and adolescentsfrom 1to 17years, and in adults.

CRYSVITA is used to treat tumor-induced osteomalacia (TIO) when the tumor causing it cannot be removed or located successfully, in children and adolescents from 1 to 17years and in adults.

What is hypophosphatemia associated with X-linked hypophosphatemia (XLH)

Hypophosphatemia associated with X-linked hypophosphatemia 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.
• The low level of phosphate may:

• result in bones not hardening correctlyand, in children and adolescents, not growing correctly;
• produce pain and stiffness in the bones and joints.

What is tumor-induced osteomalacia (TIO)

• People with TIO have higher levels of a hormone called FGF23 produced by certain types of tumors.
• FGF23 reduces the amount of phosphate in the blood.

• The low level of phosphate may produce softening of the bones, muscle weakness, fatigue, bone pain, and fractures.

How CRYSVITA works

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

Do not use CRYSVITA

• if you are allergic to burosumab or any of the other ingredients in this medicine (listed in section 6);
• if you take phosphate supplements or certain vitamin D supplements (containing the active form of vitamin D [e.g., calcitriol]);
• if you already have high levels of phosphate in your blood («hyperphosphatemia»);
• if you have severe kidney disease or kidney failure.

Allergic reactions

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

• skin rash and itching all over the body;
• severe swelling of the eyelids, mouth, or lips (angioedema);
• shortness of breath;
• rapid heart rate;
• sweating.

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

Warnings and precautions

Skin reactions

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

Tests and checks

Your doctor will check your phosphate and calcium levels in the blood and urine and may also perform a renal ultrasound during treatment to reduce the risk of hyperphosphatemia (too much phosphate in the blood) and ectopic mineralization (calcium accumulation in tissues such as the kidneys). They will also check your parathyroid hormone levels from time to time.

Children under 1 year

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

Other medicines and CRYSVITA

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

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

• phosphate supplements;
• certain vitamin D supplements (containing the active form of vitamin D [e.g., calcitriol]). There are some vitamin D supplements that you may continue to use or start using, and your doctor will indicate which ones.

Consult your doctor before starting to use CRYSVITA:

• if you are taking medicines that work in the body in the same way as calcium («calcimimetics»). If used simultaneously, they may reduce the level of calcium in the blood;
• if you have TIO and are about to receive treatment for the underlying tumor (i.e., radiation therapy or surgical removal). In this case, CRYSVITA treatment will not be initiated until after tumor treatment and if serum phosphate levels are low.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine. This is because it is unknown whether CRYSVITA will affect the baby.

CRYSVITA is not recommended during pregnancy.

If you can become pregnant, you must use an effective contraceptive method while using CRYSVITA. You should discuss this with your doctor.

It is unknown whether CRYSVITA passes into breast milk and the risk cannot be ruled out in newborns/breastfeeding infants. You should discuss this with your doctor.

Driving, cycling, and using machines

CRYSVITA may cause dizziness and affect your ability to ride a bike, use tools or machines, or drive. If you think it affects you, do not ride a bike, do not use tools or machines, and do not drive. Inform your doctor.

CRYSVITA contains sorbitol

This medicine contains 45.91 mg of sorbitol in each vial equivalent to 45.91 mg/ml.

CRYSVITA should be administered via subcutaneous injection in the upper arm, abdomen, buttock, or thigh. A healthcare professional will administer this medication to you or your child. Alternatively, your doctor may recommend that you administer it yourself or have your child administer it. A healthcare professional will show you how to do it. The first self-injection after starting treatment or after any dose change should be done in their presence. A detailed section on "Instructions for use" is included at the end of this leaflet. Always follow these instructions carefully when administering the CRYSVITA injection yourself or to your child.

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

How much CRYSVITA you will need

The dose is determined by body weight. Your doctor will calculate the correct dose for you.

Doses for XLH and TIO

You will need to inject your dose of CRYSVITA:

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

Your doctor will perform checks to ensure you receive the correct dose and can change the doseor the administration frequencyas needed.

Maximum dose for patients with XLH

The maximum dose you will receivefor the treatment of XLHis 90 mg.

Maximum dose for patients with TIO

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

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

Patients withTIO

If you are a patient with TIO who requires treatment for the underlying tumor (i.e., radiation therapy or surgical excision), your doctor will suspend CRYSVITA treatment. Once the tumor treatment is complete, your doctor will perform checks on your serum phosphate levels and restart CRYSVITA treatment if serum phosphate levels are low.

If you are given more CRYSVITA than you should

If you think you have been given an excessive amount of CRYSVITA, inform your doctor immediately.

If you miss a dose of CRYSVITA

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

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

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

Side effectsin children and adolescents with XLH

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

• Dental abscess (infection)
• Cough
• Headache
• Dizziness
• Vomiting
• Nausea
• Diarrhea
• Constipation
• Tooth decay
• Rash
• Muscle pain (myalgia) and pain in hands and feet
• Reactions at the injection site, which may include:

• Redness or rash
• Pain or itching
• Swelling
• Bleeding

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

• Fever
• Low level of vitamin D in the blood

Unknown frequency (cannot be estimated from available data))

• Increased phosphate in the blood

Side effects in children and adolescents with TIO

No side effects have been reported in children and adolescents, as no clinical studies have been conducted.

Side effects in adults with XLH and TIO

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

• Dental abscess (infection)
• Headache
• Dizziness
• Restless legs syndrome (irresistible urge to move legs to stop uncomfortable, painful, or strange sensations in legs, especially before sleep or at night)
• Constipation
• Back pain
• Muscle spasm
• Reactions at the injection site, which may include pain or swelling
• Low level of vitaminD in the blood

Common (may affect up to 1 in 10 adults)

• Rash
• Increased phosphate in the blood

Reporting of side effects

If you experience any type of side effect, consult your doctor 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 notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep CRYSVITA out of sight and reach of children.

Do not use CRYSVITA after the expiration date that appears on the box and label.

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

Store the vial in the outer box to protect it from light.

Do not use CRYSVITA if it contains visible particles.

Medicines should not be disposed of through drains or in the trash.This will help protect the environment.

If self-administered, consult step5 of the "Instructions for use" that appear at the end of the leaflet for the disposal of unused medications and materials.

If you have any doubts about how to dispose of the medications you no longer need, ask your healthcare professional or pharmacist.

Composition of CRYSVITA

The active ingredient is burosumab. Each vial contains 10, 20 or 30 mg of burosumab.

The other components are L-histidine, D-sorbitol (E420), polisorbate 80, L-methionine, hydrochloric acid 10% and water for injection. (See "CRYSVITA contains sorbitol" in section 2 for more information).

Appearance of the product and contents of the container

CRYSVITA is presented as a transparent to slightly opalescent, colorless to pale yellow/brown clear solution in a small glass vial. Each container contains 1 vial.

Marketing authorization holder

Kyowa Kirin Holdings B.V.

Bloemlaan 2

2132NP Hoofddorp

Netherlands

[email protected]

Responsible manufacturer

allphamed PHARBIL Arzneimittel GmbH

Hildebrandstr. 10-12

37081 Göttingen

Germany

Kyowa Kirin Holdings B.V.

Bloemlaan 2

2132NP Hoofddorp

Netherlands

Last review date of this leaflet:

The European Medicines Agency will review new information on this medicine at least once a year and this leaflet will be updated as necessary.

Other sources of information

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