Vysribli 60 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Vysribli 60 mg solution for injection in pre-filled syringe

denosumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information you should know before and during treatment with Vysribli.

Leaflet contents

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

1. What Vysribli is and what it is used for

What Vysribli is and how it works

Vysribli contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein in order to treat bone loss and osteoporosis. Treatment with Vysribli strengthens bones and reduces the risk of fractures.

Bone is living tissue that is constantly being renewed. Estrogens help maintain bone health. After menopause, estrogen levels decrease, which may cause bones to become thinner and more fragile. Over time, this can lead to a condition called osteoporosis. Osteoporosis can also occur in men due to various causes, including age and/or low levels of the male hormone testosterone. It may also occur in patients receiving glucocorticoid therapy. Many patients with osteoporosis do not have symptoms, yet they still have an increased risk of bone fractures, particularly in the spine, hip, and wrists.

Surgical procedures or medications that suppress the production of estrogen or testosterone, used to treat patients with prostate or breast cancer, can also cause bone loss. As a result, bones become weaker and more prone to breaking.

What Vysribli is used for

Vysribli is used to treat:

• postmenopausal osteoporosis in women and osteoporosis in men who are at increased risk of fracture (bone breakage), reducing the risk of hip, vertebral, and non-vertebral fractures.
• bone loss caused by reduced hormone levels (testosterone) resulting from surgery or medical treatment in patients with prostate cancer.
• bone loss due to long-term glucocorticoid therapy in patients who have a high risk of fracture.

2. What you need to know before using Vysribli

Do not use Vysribli:

• if you have low levels of calcium in your blood (hypocalcemia).
• if you are allergic to denosumab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Vysribli.

While being treated with Vysribli, you may develop a skin infection with symptoms such as a swollen and red area of skin, most commonly in the lower leg, which feels warm and tender to the touch (cellulitis), and which may be accompanied by fever. Inform your doctor immediately if you experience any of these symptoms.

Additionally, you should take calcium and vitamin D supplements during treatment with Vysribli. Your doctor will discuss this with you.

While receiving Vysribli, you may develop low levels of calcium in the blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, contractions or cramps, and/or numbness or tingling in the fingers, toes, or around the mouth, and/or seizures, confusion, or loss of consciousness.

Rarely, cases of very low blood calcium levels have been reported, requiring hospitalization and, in some cases, potentially life-threatening reactions. Therefore, before each dose is administered, and within two weeks after the initial dose in patients predisposed to hypocalcemia, your blood calcium levels will be checked (through a blood test).

Inform your doctor if you have or have had severe kidney problems, renal insufficiency, if you have required dialysis, or if you are taking medications called glucocorticoids (such as prednisolone or dexamethasone), as these may increase the risk of low blood calcium levels if you do not take calcium supplements.

Problems in the mouth, teeth, or jaw

In patients receiving Vysribli for osteoporosis, a rare adverse effect called osteonecrosis of the jaw (ONJ) (damage to the jaw bone) has been reported (may affect up to 1 in 1,000 people). The risk of ONJ increases in patients treated for a long time (may affect up to 1 in 200 people if treated for 10 years). ONJ can also occur after stopping treatment. It is important to try to prevent ONJ from developing, as it can be a painful condition that may be difficult to treat. To reduce the risk of developing ONJ, follow these precautions:

Before receiving treatment, inform your doctor or nurse (healthcare professional) if:

• you have any problems with your mouth or teeth, such as poor dental health, gum disease, or planned dental extraction.
• you do not receive regular dental check-ups or have not had a dental check-up for a long time.
• you are a smoker (as this may increase the risk of dental problems).
• you have previously been treated with a bisphosphonate (used to prevent or treat bone disorders).
• you are taking medications called corticosteroids (such as prednisolone or dexamethasone).
• you have cancer.

Your doctor may ask you to have a dental examination before starting treatment with Vysribli.

During treatment with Vysribli, you should maintain good oral hygiene and undergo routine dental check-ups. If you wear dentures, ensure they fit properly. If you are undergoing dental treatment or are scheduled for dental surgery (e.g., tooth extractions), inform your doctor about your dental treatment and inform your dentist that you are being treated with Vysribli.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as loose teeth, pain or swelling, or non-healing or oozing sores, as these could be symptoms of ONJ.

Unusual femur fractures

Some people have developed unusual fractures in the femur while being treated with Vysribli. Consult your doctor if you experience new or unusual pain in the hip, groin, or thigh.

Children and adolescents

Vysribli should not be used in individuals under 18 years of age.

Use of Vysribli with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. It is especially important that you inform your doctor if you are being treated with another medicine containing denosumab.

You must not use Vysribli together with another medicine containing denosumab.

Pregnancy and breastfeeding

Vysribli has not been studied in pregnant women. It is important that you inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Vysribli is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment with Vysribli and for at least 5 months after stopping treatment with Vysribli.

If you become pregnant during treatment with Vysribli or within 5 months after stopping treatment with Vysribli, inform your doctor.

It is unknown whether Vysribli is excreted in human breast milk. It is important that you inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or to stop using Vysribli, taking into account the benefits of breastfeeding for the child and the benefits of Vysribli for the mother.

If you are breastfeeding during treatment with Vysribli, please inform your doctor.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

The influence of Vysribli on the ability to drive and use machines is negligible or none.

Vysribli contains sorbitol

This medicine contains 46 mg of sorbitol per ml of solution.

Vysribli contains polysorbate 20

This medicine contains 0.1 mg of polysorbate 20 in each 1 ml pre-filled syringe. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

Vysribli contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 60 mg; hence, it is essentially “sodium-free”.

3. How to use Vysribli

The recommended dose is one pre-filled syringe of 60 mg administered under the skin (subcutaneous route) as a single injection every 6 months. The best sites for the injection are the upper thighs and the abdomen. If the injection is given by a caregiver, the injection may also be administered into the outer side of the upper arm. Consult your doctor for the date of your next possible injection. Each Vysribli pack contains a detachable label that can be removed from the blister and used to keep a record of the date of your next injection.

In addition, you must take calcium and vitamin D supplements during treatment with Vysribli. Your doctor will discuss this with you.

Your doctor may decide whether it is better for you or a caregiver to administer the Vysribli injection. Your doctor or healthcare professional will show you or your caregiver how to use Vysribli. If you would like instructions on how to inject Vysribli, please read the last section of this leaflet.

Do not shake.

If you forget to use Vysribli

If you miss a dose of Vysribli, the injection should be given as soon as possible. After that, injections should be scheduled every 6 months from the date of the last injection.

If you stop using Vysribli

To get the maximum benefit from your treatment and to reduce the risk of fractures, it is important that you use Vysribli for the entire period prescribed by your doctor. Do not stop treatment without first speaking to your doctor.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

Patients treated with Vysribli may occasionally develop skin infections (mainly cellulitis). Contact your doctor immediately if any of the following symptoms occur during treatment with Vysribli: swollen, red area of skin, usually on the lower leg, which is warm and tender to the touch and may be accompanied by fever.

Rarely, patients receiving Vysribli may develop pain in the mouth and/or jaw, swelling or non-healing ulcers in the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or loose teeth. These could be symptoms of bone damage in the jaw (osteonecrosis). Contact your doctor and dentist immediately if you experience such symptoms while being treated with Vysribli or after stopping treatment.

Rarely, patients receiving Vysribli may develop low levels of calcium in the blood (hypocalcemia); very low calcium levels may require hospitalization and could even be life-threatening. Symptoms include muscle spasms, twitching or cramps, and/or numbness or tingling in the hands, feet, or around the mouth and/or seizures, confusion, or loss of consciousness. If you experience any of these, contact your doctor immediately. Low calcium levels in the blood may also cause a change in heart rhythm known as QT prolongation, which can be detected by an electrocardiogram (ECG).

Rarely, unusual femoral fractures may occur in patients receiving Vysribli.

Consult your doctor if you experience new or unusual pain in the hip, groin, or thigh, as this may be an early sign of a possible femoral fracture.

Rarely, allergic reactions may occur in patients receiving Vysribli. Symptoms include swelling of the face, lips, tongue, throat, or other parts of the body; skin rash, itching, or hives; wheezing or difficulty breathing. Contact your doctor if you experience such symptoms while being treated with Vysribli.

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

• bone, joint, and/or muscle pain, sometimes severe,
• pain in legs or arms (limb pain).

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

• painful urination, frequent urination, blood in the urine, urinary incontinence,
• upper respiratory tract infection,
• pain, tingling, or numbness radiating down the lower leg (sciatica),
• constipation,
• abdominal discomfort,
• skin rash,
• skin condition with itching, redness and/or dryness (eczema),
• hair loss (alopecia).

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

• fever, vomiting, and abdominal pain or discomfort (diverticulitis),
• ear infection,
• skin rash or mouth ulcers (drug-induced lichenoid eruptions).

Rare adverse effects (may affect up to 1 in 10,000 people):

• allergic reaction that may damage blood vessels, mainly in the skin (e.g., purple or reddish-brown spots, hives, or skin ulcers) (hypersensitivity vasculitis).

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

• consult your doctor if you have ear pain, ear discharge, and/or an ear infection. These could be symptoms of damage to the ear bones.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Vysribli

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and the carton after “CAD” or “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

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

Before injection, the pre-filled syringe may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) to make the injection more comfortable. Once the syringe has reached room temperature (up to 25 °C), it must be used within 30 days.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Vysribli

• The active substance is denosumab. Each 1 ml pre-filled syringe contains 60 mg of denosumab (60 mg/mL).
• The other components are glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20, and water for injections (see section 2, Vysribli contains sorbitol, Vysribli contains polysorbate 20, and Vysribli contains sodium).

Appearance of Vysribli and contents of the pack

Vysribli is a transparent, colourless to pale yellow injectable solution (for injection), supplied in a ready-to-use pre-filled syringe.

Each pack contains one pre-filled syringe with a needle protective cap.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Intas Third Party Sales 2005, S.L.

World Trade Center, Moll de Barcelona, s/n

Edifici Est, 6a Planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp. z.o.o.

Ul. Lutomierska 50, 95-200,

Pabianice, Poland

Kymos S.L.

Parc Tecnològic del Vallès, Ronda de Can Fatjó, 7B.

08290 Cerdanyola del Vallès, Barcelona, Spain

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

AT/BE/BG/CY/CZ/DK/EE/EL/FI/FR/HR/HU/IE/IS/IT/LT/LV/LU/MT/NL/NO/PL/PT/RO/SE/SI/SK

Intas Third Party Sales 2005, S.L.

Tel: +34 93 301 7351

DE

Altamedics GmbH

Phone: +49 221 277 299 100

ES

Meiji Pharma Spain, S.A.

Tel: +34 91 887 09 80

Date of the most recent revision of this leaflet: <{MM/YYYY}><{month YYYY}>.

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu