Evfraxy

Package leaflet: Information for the patient

Evfraxy 60 mg solution for injection in pre-filled syringe

denosumab
▼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 because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult 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, inform 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 Evfraxy.

Contents of this leaflet

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

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

Evfraxy contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, for the treatment of bone loss and osteoporosis. Treatment with Evfraxy 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 for various reasons, including ageing and/or low levels of the male hormone testosterone. It may also occur in patients receiving glucocorticoids. Many patients with osteoporosis have no symptoms, but are still at risk of bone fractures, especially in the spine, hip and wrists.
Surgical procedures or medications that stop the production of oestrogen or testosterone, used to treat patients with breast or prostate cancer, can also cause bone loss. Bones then become more fragile and more likely to fracture.
For what type of treatment is Evfraxy used?
Evfraxy is used for the treatment of:

• osteoporosis in postmenopausal women (postmenopausal osteoporosis) and in men who are at 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 drug 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 should know before using Evfraxy Do not use Evfraxy

• 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 Evfraxy.
While being treated with Evfraxy, 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. Immediately inform your doctor if you experience any of these symptoms.
While being treated with Evfraxy, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
While being treated with Evfraxy, you may have low levels of calcium in your blood. Immediately inform your doctor 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, severe low levels of calcium in the blood have been reported, leading to hospitalization and even life-threatening reactions. Therefore, before each dose and in patients at risk of developing hypocalcemia within two weeks after the initial dose, your blood calcium levels will be monitored (through blood tests).
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/mandible (severe deterioration of the jaw/mandible bone tissue) has been reported rarely (may occur in up to 1 in 1,000 patients) in patients receiving denosumab for osteoporosis. The risk of osteonecrosis of the jaw/mandible increases in patients treated for a long duration (may occur in up to 1 in 200 patients if treated for 10 years). Osteonecrosis of the jaw/mandible may also occur after stopping treatment. It is important to try to prevent the development of osteonecrosis of the jaw/mandible, as it is a painful condition that may be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw/mandible, take the following 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 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 Evfraxy.
While on treatment, it is important to maintain good oral hygiene and to have regular 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 the dental treatment and inform your dentist that you are being treated with Evfraxy.
Contact your doctor and dentist immediately if you notice any new problems with your mouth or teeth such as tooth loss, 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/mandible (ONJ).

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

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

Other medicines and Evfraxy
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 Evfraxy together with other medicines containing denosumab.

Pregnancy and breastfeeding
Evfraxy 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 are planning to become pregnant. The use of Evfraxy is not recommended if you are pregnant. Women of childbearing potential must use effective contraceptive methods while taking Evfraxy and for at least 5 months after stopping treatment with Evfraxy.
If you become pregnant during treatment with Evfraxy or within 5 months after stopping treatment with Evfraxy, please inform your doctor.
It is not known whether denosumab passes into breast milk. It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will then help you decide whether to stop breastfeeding or stop taking Evfraxy, considering the benefit of breastfeeding for the child and the benefit of taking Evfraxy for the mother.
If you are breastfeeding during treatment with Evfraxy, inform your doctor.
Ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines
Evfraxy does not alter or alters negligibly the ability to drive or use machines.

Evfraxy contains sorbitol
This medicine contains 47 mg of sorbitol per mL of solution.

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

Evfraxy contains Polysorbate 20
This medicine contains 0.1 mg of polysorbate 20 in each 60 mg/mL pre-filled syringe, equivalent to 0.1 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Evfraxy

The recommended dose is one pre-filled syringe containing 60 mg administered once every 6 months,
as a single subcutaneous injection (under the skin). The most suitable injection sites are the upper thigh and the abdomen. If an assistant is giving the injection, the upper outer area of the arm may also be used. Consult your doctor regarding the date of your next possible injection. Each Evfraxy package contains a reminder card, which can be removed from the box and used to keep track of the date of your next injection.
During treatment with Evfraxy, 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 for your assistant to administer the Evfraxy injection. Your doctor or nursing staff will show you or your assistant how to administer Evfraxy. For instructions on how to inject Evfraxy, refer to the section at the end of this leaflet.
Do not shake.
If you forget to use Evfraxy
If you have forgotten a dose of Evfraxy, the injection should be given as soon as possible.
Afterwards, injections should be given every 6 months from the date of the last injection.
If you stop using Evfraxy
To obtain the maximum benefit from treatment in reducing the risk of fractures, it is important to use Evfraxy 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 everyone experiences them.
Uncommonly, patients treated with Evfraxy may develop skin infections (especially cellulitis). Inform your doctor immediately if any of the following symptoms occur while you are taking Evfraxy: skin redness and swelling, most commonly in the lower leg, accompanied by warmth, pain, and possibly fever.
Rarely, patients treated with Evfraxy may experience pain in the mouth and/or jaw, swelling or non-healing lesions in the mouth or jaw, discharge, numbness or a sensation of heaviness in the jaw, or loose teeth. These could be signs of a serious deterioration of the jawbone (osteonecrosis). Inform your doctor and dentist immediately if you experience any of these symptoms during or after treatment with Evfraxy.
Rarely, patients treated with Evfraxy may have low levels of calcium in the blood (hypocalcemia); severe hypocalcemia may require hospitalization and can even be life-threatening. 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. Inform your doctor immediately if any of these symptoms occur. Low calcium levels in the blood may also lead to changes in heart rhythm known as QT interval prolongation, which can be detected by electrocardiogram (ECG).
Rarely, atypical femoral fractures may occur in patients treated with Evfraxy. Contact your doctor if you develop 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 treated with Evfraxy. Symptoms include swelling of the face, lips, tongue, throat, or other body parts; rash, itching, hives, wheezing, or difficulty breathing. Inform your doctor if you experience any of these symptoms during treatment with Evfraxy.

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 the 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 eruptions 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 affecting the skin (e.g. purple or red-brown spots, hives, or skin ulcers) (hypersensitivity vasculitis).

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

• inform your doctor if you experience ear pain, ear discharge, and/or ear infection. These could 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 listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Evfraxy

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the carton after Exp. The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C – 8 °C). Do not freeze.
Keep the container 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 no longer required. This will help protect the environment.

6. Package contents and other information What is in Evfraxy

• 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 acetate trihydrate, sodium hydroxide, sorbitol, polysorbate 20 and water for injections.

Description of the appearance of Evfraxy and contents of the pack
Evfraxy is an injectable solution ranging from clear to slightly opalescent, colourless to pale yellow, supplied in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with needle protection.
Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36, Grange Parade, Baldoyle Industrial Estate,
Dublin 13,
Dublin, Ireland, D13 R20R
Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building,
Santry, Demesne,
Dublin, D09 C6X, Ireland
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Biocon Biologics Belgium BV Biosimilar Collaborations Ireland Limited
Tél/Tel: 0080008250910 Tel: 0080008250910
България Luxembourg/Luxemburg
Biosimilar Collaborations Ireland Limited Biocon Biologics France S.A.S
Тел: 0080008250910 Tél/Tel: 0080008250910
(Belgique/Belgien)
Česká republika Magyarország
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel.: 0080008250910
Danmark Malta
Biocon Biologics Finland OY Biosimilar Collaborations Ireland Limited
Tlf: 0080008250910 Tel.: 0080008250910
Deutschland Nederland
Biocon Biologics Germany GmbH Biocon Biologics France S.A.S
Tel: 0080008250910 Tel: 0080008250910
Eesti Norge
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Tel: 0080008250910 Tlf: +47 800 62 671
Ελλάδα Österreich
Biocon Biologics Greece ΜΟΝΟΠΡΟΣΩΠΗ Biocon Biologics Germany GmbH
Ι.Κ.Ε Tel: 0080008250910
Τηλ.: 0080008250910
España Polska
Biocon Biologics Spain S.L. Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910
France Portugal
Biocon Biologics France S.A.S Biocon Biologics Spain S.L.
Tel: 0080008250910 Tel: 0080008250910
Hrvatska România
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910
Ireland Slovenija
Biosimilar Collaborations Ireland Limited Biosimilar Collaborations Ireland Limited
Tel: 1800 777 794 Tel: 0080008250910
Ísland Slovenská republika
Biocon Biologics Finland OY Biocon Biologics Germany GmbH
Sími: +345 800 4316 Tel: 0080008250910
Italia Suomi/Finland
Biocon Biologics Spain S.L. Biocon Biologics Finland OY
Tel: 0080008250910 Puh/Tel: 99980008250910
Κύπρος Sverige
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Τηλ: 0080008250910 Tel: 0080008250910
Latvija
Biosimilar Collaborations Ireland Limited
Tel: 0080008250910
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/
Instructions for use:
Parts guide
Before use After use

Figure A
Important information
Read the Patient Information Leaflet, which contains important information about Evfraxy,
before using these Instructions for Use.
Before using a pre-filled syringe of Evfraxy with automatic needle protection,
read the following important information:
It is important not to attempt to administer the injection yourself unless you have been trained by your doctor or a healthcare professional.
The pre-filled syringe is equipped with a safety needle shield that automatically activates to cover the needle after injection. The needle shield helps prevent needle-stick injuries for anyone handling the syringe after injection.
Ensure that the name Evfraxy is visible on the packaging and on the syringe label.
Evfraxy is administered as an injection into the tissue just beneath the skin (subcutaneous injection).
Do not use the pre-filled syringe if the packaging is open or damaged.
Do not remove the grey needle cap from the pre-filled syringe until you are ready to inject.
Do not use the pre-filled syringe if it has been dropped onto a hard surface. In this case, 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 try to remove the transparent safety shield of the pre-filled syringe.
Do not use the pre-filled syringe if it is broken, already activated, or separated from the needle shield.
Contact your doctor or healthcare professional if you have any questions.
Storage of the Evfraxy pre-filled syringe
Store Evfraxy in the refrigerator at a temperature between 2°C and 8°C in its original packaging.
Do not freeze. Before administration, Evfraxy may be kept at room temperature (up to 25°C) in its original container.
After removal from the refrigerator, Evfraxy must not be exposed to temperatures above 25°C and must be used within 30 days. If not used within 30 days, Evfraxy must be discarded. See Step 4: Disposal of used pre-filled syringes.
Step 1: Gather materials
Identify a clean, well-lit, flat work surface.
Remove the pre-filled syringe pack from the refrigerator and place it on the clean work surface. Allow it to reach room temperature for 30 minutes before administering the injection.
Remove the pre-filled syringe tray from the packaging.
Wash your hands thoroughly with soap and water.
Gather the necessary materials for injection (not included) Figure B:
alcohol wipes
cotton ball or gauze pad
adhesive bandage
sharps disposal container

Do not attempt to warm the syringe using a heat source such as hot water or a microwave.
Do not leave the pre-filled syringe exposed to direct sunlight.
Do not shake the pre-filled syringe.

• Keep the pre-filled syringe out of the sight and reach of children. Figure B

Step 2: Prepare the injection
Open the tray by peeling back the cover to remove it. Grasp the safety shield of the pre-filled syringe to remove the syringe from its casing (Figure C).

Grasp here
Figure C
For safety reasons:
Do not grasp the plunger.
Do not grasp the grey needle cap.
Inspect the medicine and the pre-filled syringe (Figure D).

Figure D
Do not use the pre-filled syringe if:

• the medicine is cloudy or contains particles. It should be a clear or slightly opalescent solution, colourless to pale yellow;
• any part appears cracked or broken;
• the grey needle cap is missing or not securely attached;
• the expiry date printed on the label has passed the last day of the month indicated.

In any of these cases, use a new pre-filled syringe and contact your doctor or healthcare professional.
Wash your hands thoroughly. Prepare and clean the injection site.
You may use (Figure E):
The upper thigh.
The abdomen, avoiding an area within 5 cm of the navel.
The outer upper arm (only if someone else is administering the injection).

Figure E
Clean the injection site with an alcohol wipe. Wait for the skin to dry.
Do not touch the injection site before injecting.
Do not inject into areas where the skin is tender, bruised, red, or hardened.
Avoid injecting into areas with scars or stretch marks.
Hold the pre-filled syringe by the needle shield. When ready, carefully remove the grey needle cap by pulling it straight off and away from the syringe body (Figure F).

Figure F
Do not twist or bend the grey needle cap.
Do not hold the pre-filled syringe by the plunger rod.
Dispose of the grey needle cap in the sharps disposal container.
Pinch the injection site to create a taut skin surface (Figure G).

Figure G
! It is important to keep the skin taut during injection.
Step 3: Injection
Hold the skin taut. Insert the needle into the skin (Figure H).

Figure H
Do not touch the cleaned area of skin.
Push the plunger with slow, steady pressure until you feel or hear a "click". Continue pushing until the plunger stops completely (Figure I).

Figure I
It is important to push fully until the "click" to deliver the full dose.
Once the full dose has been injected, the needle shield will activate. You may then proceed in one of the following two ways (see Figure J):
Release the plunger until the entire needle is covered, then remove the needle from the injection site.
Or
Gently remove the needle from the injection site and then release the plunger until the entire needle is covered by the safety needle shield.

Figure J
After releasing the plunger, the safety shield of the pre-filled syringe will securely cover the injection needle.
If the needle shield does not activate or only partially activates, discard the product (without replacing the needle cap). See "Step 4: Disposal of used pre-filled syringes".
Do not replace the grey needle cap onto used pre-filled syringes.
Examine the injection site.
If there is bleeding, apply a cotton ball or gauze pad to the injection site. Do not rub the injection site. Apply an adhesive bandage if needed.
Step 4: Disposal of used pre-filled syringes
Dispose of the used pre-filled syringe and other materials in a sharps disposal container (Figure K).

Figure K
Medicines must 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 used syringe and the sharps disposal container out of the 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.