Osvyrti

Package leaflet: Information for the user

Osvyrti 60 mg solution for injection in pre-filled syringe

denosumab
This medicinal product is subject to additional monitoring. This will allow for 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 because it contains important information for you.

• 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 their symptoms are the same as yours, as 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.
• Your doctor will provide you with a patient reminder card containing important safety information that you must know before and during treatment with Osvyrti.

Contents of this leaflet

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

1. What Osvyrti is and what it is used for What Osvyrti is and how it works

OSVYRTI contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, for the treatment of bone loss and osteoporosis. Treatment with Osvyrti makes bones stronger and less prone to fractures.
Bone is a living tissue that is constantly being renewed. Oestrogens help maintain healthy bones. After menopause, reduced oestrogen levels can make bones thin and fragile, which may lead to the development of a condition called osteoporosis. Osteoporosis can also occur in men due to various causes, including ageing and/or low levels of the male hormone testosterone. It can also occur in patients receiving glucocorticoids. Many patients with osteoporosis do not have symptoms, but are still at risk of bone fractures, particularly in the spine, hip, and wrists.
Surgical procedures or medications that suppress the production of oestrogen or testosterone, used in the treatment of patients with breast or prostate cancer, can also cause bone loss. As a result, bones become more fragile and more likely to fracture.
For which type of treatment is Osvyrti used?
Osvyrti is used for the treatment of:

• osteoporosis in postmenopausal women (postmenopausal osteoporosis) and in men who have an increased risk of fractures (broken bones), to reduce the risk of vertebral, non-vertebral, and hip fractures.
• bone loss in men due to reduced hormone levels (testosterone) caused by surgery or pharmacological therapy in patients with prostate cancer.
• bone loss due to long-term treatment with glucocorticoids in patients at increased risk of fracture.

2. What you need to know before using Osvyrti

Do not use Osvyrti

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

Warnings and precautions
Talk to your doctor or pharmacist before using Osvyrti.
While being treated with Osvyrti, you may develop a skin infection with symptoms such as swelling, redness, most commonly in the lower leg, with a feeling of warmth and pain (cellulitis), and possibly fever. Inform your doctor immediately if you experience any of these symptoms.
While being treated with Osvyrti, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
While being treated with Osvyrti, you may have low levels of calcium in your blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, twitching or cramps, and/or numbness or tingling in the fingers, toes or around the mouth, and/or seizures, confusion or loss of consciousness.
In rare cases, severely low levels of calcium in the blood have been reported, leading to hospitalization and even life-threatening reactions. Therefore, your blood calcium levels will be monitored (through a blood test) before each dose and, in patients at risk of developing hypocalcemia, within two weeks after the initial dose.
Inform your doctor if you have or have ever had severe kidney problems, impaired kidney function, if you are on dialysis, or if you are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), as these may increase your risk of low blood calcium levels if you do not take calcium supplements.

Problems with mouth, teeth or jaw
A side effect called osteonecrosis of the jaw (severe deterioration of the jawbone) has been reported rarely (may occur in up to 1 in 1,000 patients) in patients receiving Osvyrti for osteoporosis. The risk of osteonecrosis of the jaw increases in patients treated for a long period (may occur in up to 1 in 200 patients if treated for 10 years). Osteonecrosis of the jaw may also occur after stopping treatment. It is important to try to prevent the development of osteonecrosis of the jaw, as it is a painful condition that can be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, take the following precautions:
Before receiving treatment, inform your doctor or nurse (healthcare provider) if you:

• have any mouth or dental problems, such as poor dental hygiene, gum disorders, or if you are scheduled for a tooth extraction;
• do not regularly receive dental care or have not had a dental check-up for a long time;
• are a smoker (as this may increase the risk of dental problems);
• have previously been treated with a bisphosphonate (used to treat or prevent bone disorders);
• are taking medicines called corticosteroids (such as prednisolone or dexamethasone);
• have cancer.

Your doctor may ask you to have a dental examination (by a dentist) before starting treatment with Osvyrti.
During treatment, you must maintain good oral hygiene and have regular dental check-ups. If you wear dentures, ensure they are properly fitted. If you are currently undergoing dental treatment or are scheduled for dental surgery (e.g., tooth extractions), inform your doctor about the dental treatment and inform your dentist that you are being treated with Osvyrti.
Contact your doctor and dentist immediately if you notice any new mouth or dental problems such as loose teeth, pain or swelling, or failure of mouth sores to heal, or discharge, as these could be signs of a side effect called osteonecrosis of the jaw (ONJ).

Atypical femoral fractures
Some people have developed atypical fractures of the femur during treatment with Osvyrti.
Contact your doctor if you experience new or unusual pain in your hip, groin, or thigh.

Children and adolescents
Osvyrti must not be used in children and adolescents under 18 years of age.

Other medicines and Osvyrti
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform your doctor if you are taking other medicines containing denosumab.
You must not take Osvyrti together with other medicines containing denosumab.

Pregnancy and breastfeeding
Osvyrti has not been studied in pregnant women. It is important that you inform your doctor if you are pregnant; if you think you may be pregnant; or if you are planning a pregnancy. The use of Osvyrti is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Osvyrti and for at least 5 months after stopping treatment with Osvyrti.
If you become pregnant during treatment with Osvyrti or within 5 months after stopping treatment with Osvyrti, please inform your doctor.
It is not known whether Osvyrti passes into breast milk. It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or Osvyrti, taking into account the benefit of breastfeeding for the child and the benefit of Osvyrti for the mother.
If you are breastfeeding during treatment with Osvyrti, inform your doctor.
Ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines
Osvyrti has no effect or negligible effect on the ability to drive and use machines.

Osvyrti contains sorbitol
This medicine contains 46 mg of sorbitol per mL of solution.

Osvyrti contains polysorbate 20
This medicine contains 0.1 mg of polysorbate 20 in each 1 mL pre-filled syringe. Polysorbates may cause allergic reactions. If you have any known allergy, inform your doctor.

Osvyrti contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 60 mg, i.e., essentially ‘sodium-free’.

3. How to use Osvyrti

The recommended dose is one pre-filled syringe containing 60 mg administered once every 6 months as a single subcutaneous (under the skin) injection. The most suitable injection sites are the upper thighs and the abdomen. If an assistant is administering the injection, the outer upper arm may also be used. Consult your doctor regarding the date of your next possible injection.
Each Osvyrti pack contains a detachable label, which can be removed from the blister and used to record the date of the next injection.
During treatment with Osvyrti, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
Your doctor will decide whether it is better for you or your assistant to administer the Osvyrti injection. Your doctor or nursing staff will show you or your assistant how to use Osvyrti. For instructions on how to inject Osvyrti, see the section at the end of this leaflet.
Do not shake.

If you forget to use Osvyrti
If you have missed a dose of Osvyrti, the injection should be given as soon as possible.
Afterwards, injections should continue to be given every 6 months from the date of the last injection.

If you stop using Osvyrti
To achieve the maximum benefit from treatment in reducing the risk of fractures, it is important to use Osvyrti for the entire duration prescribed by your doctor. Do not stop treatment without consulting your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Infections of the skin (especially cellulitis) may occur uncommonly in patients treated with Osvyrti. Contact your doctor immediately if you experience any of the following symptoms while taking Osvyrti: skin redness and swelling, most commonly in the lower leg, with a feeling of warmth and pain, possibly accompanied by fever.

Rarely, patients treated with Osvyrti may develop pain in the mouth and/or jaw, swelling or non-healing sores in the mouth or jaw, discharge, numbness or a sensation of heaviness in the jaw, or loose teeth. These may be signs of severe bone deterioration in the jaw (osteonecrosis). Contact your doctor and dentist immediately if you experience any of these symptoms during or after stopping treatment with Osvyrti.

Rarely, patients treated with Osvyrti may have low levels of calcium in the blood (hypocalcaemia). Symptoms include muscle spasms, twitching or cramps, and/or numbness or tingling in the fingers, toes or around the mouth, and/or seizures, confusion, or loss of consciousness. Contact your doctor immediately if you experience any of these symptoms. Low calcium levels in the blood may also lead to changes in heart rhythm known as QT interval prolongation, which can be detected by an electrocardiogram (ECG).

Rarely, atypical femoral fractures may occur in patients treated with Osvyrti. Contact your doctor if you develop new or unusual pain in your hip, groin, or thigh, as this may be an early sign of a possible femoral fracture.

Rarely, allergic reactions may occur in patients treated with Osvyrti. Symptoms include swelling of the face, lips, tongue, throat or other body parts; rash, itching, hives, wheezing or difficulty breathing. Contact your doctor if you experience any of these symptoms during treatment with Osvyrti.

Very common side effects (may occur in more than 1 in 10 people):

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

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

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

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

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

Very rare side effects (may occur in up to 1 in 10,000 people):

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

Not known (frequency cannot be estimated from the available data):

• contact your doctor if you experience ear pain, ear discharge, and/or an ear infection. These may be signs of damage to the ear bone.

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

5. How to store Osvyrti

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
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
The pre-filled syringe may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) before injection. This will make the injection more comfortable.
Once the syringe has reached room temperature (up to 25 °C), it must be used within 30 days.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information What Osvyrti contains

• 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, Osvyrti contains sorbitol, Osvyrti contains polysorbate 20 and Osvyrti contains sodium).

Description of the appearance of Osvyrti and contents of the pack
Osvyrti is a clear, colourless to pale yellow injectable solution (injection) in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with needle protection.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Accord Healthcare S.L.U.
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
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT /
NL / NO / PL / PT / RO / SE / SI / SK
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Α.Ε.
Tel: +30 210 74 88 821
Other sources of information
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:

Guide to the parts

Before use
After use
Important
Before using an Osvyrti pre-filled syringe with automatic needle protection, read
these important instructions:

• • It is important that you do not attempt to perform the injection unless you have received adequate instructions from your doctor or healthcare professional.
• • Osvyrti is administered as an injection into the tissue just beneath the skin (subcutaneous injection). Do not remove the grey cap/needle cover from the pre-filled syringe until you are ready to inject.

Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare professional.

Do not attempt to activate the pre-filled syringe before injection.

Do not touch the needle shield activation clips before use; otherwise, the syringe's needle protection may activate prematurely.

Do not attempt to remove the clear safety shield from the pre-filled syringe.

Contact your doctor or healthcare professional if you have any questions.

B Open the pouch by tearing off the cover. Grasp the safety shield of the prefilled syringe
to remove the prefilled syringe from the pouch.

Grasp here
For safety reasons:
Do not grasp the plunger.

Do not grasp the grey cap/the needle cover.
C Check the medicine and the prefilled syringe.

Medicine window
Do not use the prefilled syringe if:

• The medicine is cloudy or contains particles. It should be a clear, colourless to pale yellow solution.
• Any parts appear cracked or broken.
• The grey cap/the needle cover is missing or not securely attached.
• The expiry date printed on the label has passed the last day of the month indicated. In all these cases, contact your doctor or healthcare provider.

Step 2: Preparation
A Wash your hands thoroughly. Prepare and clean the injection site.

Upper arm
Abdomen
Upper thigh
You may use:

• The upper thigh.
• The abdomen, except for the area within 5 centimetres around the navel.
• The outer upper arm (only if someone else administers the injection). Clean the injection site with an alcohol swab. Let the skin dry. Do not touch the injection site before injecting.

Do not inject into areas where the skin is tender, injured, red, or hardened. Avoid injecting into areas

with scars or stretch marks.

B Tc	Carefully remove the gray cap/needle cover by pulling it outward and away from the body.
Do not twist or bend the cap/needle cover. Do not hold the pre-filled syringe by the plunger rod. Dispose of the cap/needle cover into a sharps disposal container. Do not touch the needle and avoid contact between the needle and any surface. Do not recap the needle.
C S	Lift the injection site to create a stable surface.
It is important to keep the skin lifted during injection.
Step 3: Injection
A	Keep the skin lifted. INSERT the needle into the skin.
Do not touch the clean area of the skin.
B	PUSH the plunger with slow and steady pressure until you feel or hear a "click". Push fully until the click is reached.
It is important to push fully until the "click" to ensure the full dose is injected.
C	RELEASE the thumb. Then REMOVE the syringe from the skin.
After releasing the plunger, the safety shield of the pre-filled syringe will automatically cover the injection needle safely. Do not replace the gray needle cap onto used pre-filled syringes.

Step 4: Disposal
Dispose of the used pre-filled syringe and other materials in a sharps disposal container.

Medicines should be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.
Keep the syringe and the sharps disposal container out of sight and reach of children.
Do not reuse the pre-filled syringe.

Do not recycle pre-filled syringes or dispose of them in household waste.