Evfraxy 60 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Evfraxy 60 mg solution for injection in pre-filled syringe

denosumab

This medicinal product is subject to additional monitoring, which will allow rapid identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 includes information on how to report adverse reactions.

Read all of this leaflet carefully before you start using this medicine, because 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 adverse reactions, talk to your doctor or pharmacist, even if they are adverse reactions 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 your 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 how it works and what it is used for

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

Bone is living tissue that is constantly being renewed. Oestrogens help maintain bone health. After menopause, oestrogen levels decline, 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 can also occur in patients being treated with glucocorticoids. 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 oestrogen or testosterone, used to treat patients with breast or prostate cancer, can also cause bone loss. As a result, bones become weaker and more prone to breaking.

What Evfraxy is used for

Evfraxy is used to treat:

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

2. What you need to know before using Evfraxy

Do not use Evfraxy:

• if you have low levels of calcium in the 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 starting to use Evfraxy.

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

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

While receiving Evfraxy, you may experience 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.

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

Inform your doctor if you have or have had severe kidney problems, renal failure, if you have required 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

In patients receiving denosumab for osteoporosis, a rare adverse effect called osteonecrosis of the jaw (ONJ) (damage to the jawbone) 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 may 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 medicines called corticosteroids (such as prednisolone or dexamethasone).
• you have cancer.

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

During treatment with Evfraxy, 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 Evfraxy.

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 Evfraxy. Consult your doctor if you experience new or unusual pain in the hip, groin or thigh.

Children and adolescents

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

Using Evfraxy 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 to inform your doctor if you are being treated with another medicine containing denosumab.

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

Pregnancy and breastfeeding

Evfraxy has not been studied in pregnant women. It is important to inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Use of Evfraxy during pregnancy is not recommended. Women of childbearing potential should use effective contraception during treatment with 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, inform your doctor.

It is unknown whether denosumab is excreted in human breast milk. It is important to 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 Evfraxy, taking into account the benefits of breastfeeding for the child and the benefits of Evfraxy for the mother.

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

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

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

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 any allergies.

3. How to use Evfraxy

The recommended dose is one pre-filled syringe containing 60 mg administered under the skin (subcutaneously) as a single injection every 6 months. The best places to administer the injection are the upper thighs and the abdomen. If a caregiver (a person who assists you) is giving the injection, it may also be administered into the outer side of the upper arm. Consult your doctor to determine the date of your next possible injection. Each Evfraxy package contains a reminder card that can be detached from the carton and used to keep a record of the date of your next injection.

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

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

Do not shake.

If you forget to use Evfraxy

If you miss a dose of Evfraxy, the injection should be administered as soon as possible.

After that, injections should be scheduled every 6 months starting from the date of the last injection.

If you stop using Evfraxy

To obtain the maximum benefit from your treatment and to reduce the risk of fractures, it is important to use Evfraxy 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 can cause adverse effects, although not everyone will experience them.

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

Rarely, patients receiving Evfraxy 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 Evfraxy or after stopping treatment.

Rarely, patients receiving Evfraxy 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, contractions, or cramps, and/or numbness or tingling in the fingers, toes, 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 femur fractures may occur in patients receiving Evfraxy. 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 femur fracture.

Rarely, allergic reactions may occur in patients receiving Evfraxy. 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 Evfraxy.

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

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

Very 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 bones of the ear.

Reporting of adverse effects

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

5. Storage of Evfraxy

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 medicine in the original container 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 less uncomfortable. 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 you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of 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.

Appearance of Evfraxy and contents of the pack

Evfraxy is a slightly opalescent to clear, pale yellow to colourless injectable solution in a ready-to-use pre-filled syringe.

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

Marketing Authorization 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 C6X8 Ireland

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.euopa.eu/

• Inspect the medicine and the pre-filled syringe (ImageD).