Enwylma 120 mg solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Enwylma 120 mg solution for injection

denosumab

This medicinal product is subject to additional monitoring, which will allow rapid identification of new information on its safety. You can help by reporting any side effects you may experience. The end of section 4 includes information on how to report side effects.

Read this entire 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, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, 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 Enwylma.

Contents of this leaflet

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

1. What Enwylma is and what it is used for

Enwylma contains denosumab, a protein (monoclonal antibody) that slows down bone destruction occurring when cancer spreads to the bones (bone metastases) or in giant cell tumor of bone.

Enwylma is used in adults with advanced cancer to prevent serious complications caused by bone metastases (e.g., fractures, spinal cord compression, or the need for radiotherapy or surgery).

Enwylma is also used to treat giant cell tumor of bone that cannot be treated with surgery, or when surgery is not the best option, in adults and adolescents whose bones have stopped growing.

2. What you need to know before using Enwylma

Do not use Enwylma

• if you are allergic to denosumab or to any of the other ingredients of this medicine (listed in section 6).

Your healthcare professional will not administer Enwylma to you if you have untreated low blood calcium levels.

Your healthcare professional will not administer Enwylma to you if you have unhealed wounds from dental or oral surgery.

Warnings and precautions

Talk to your doctor before starting treatment with Enwylma.

Calcium and vitamin D supplements

You should take calcium and vitamin D supplements during treatment with Enwylma unless your blood calcium levels are high. Your doctor will explain this to you. If your blood calcium level is low, your doctor may decide to prescribe calcium supplements before starting treatment with Enwylma.

Low blood calcium levels

Contact your doctor immediately if you experience muscle spasms, twitches or cramps and/or numbness or tingling in your fingers, toes or around your mouth and/or seizures, confusion or loss of consciousness during treatment with Enwylma. Your blood calcium level may be low.

Kidney problems

Tell your doctor if you have or have had severe kidney problems, kidney failure or if you have required dialysis, as this may increase the risk of low blood calcium levels, especially if you do not take calcium supplements.

Problems with mouth, teeth and jaw

Osteonecrosis of the jaw (damage to the jawbone) has been frequently reported (may affect up to 1 in 10 people) in patients receiving injectable Enwylma for cancer-related conditions. 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 can be a painful condition that may be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, you should take the following precautions:

• Before receiving treatment, inform your doctor or nurse (healthcare professional) if you have any problems with your mouth or teeth. Your doctor should delay the start of your treatment if you have unhealed wounds in your mouth due to dental procedures or oral surgery. Your doctor will recommend a dental examination before starting treatment with Enwylma.
• While being treated, you should maintain good oral hygiene and have regular dental check-ups. If you wear dentures, make sure 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 Enwylma.
• Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as loose teeth, pain or swelling, non-healing or oozing sores, as these could be signs of osteonecrosis of the jaw.

Patients undergoing chemotherapy and/or radiotherapy, taking steroids or anti-angiogenic medicines (used to treat cancer), who have undergone dental surgery, who do not have regular dental check-ups, who have gum disease or who smoke may have an increased risk of developing osteonecrosis of the jaw.

Unusual fractures of the thigh bone

Some people have developed unusual fractures of the thigh bone during treatment with Enwylma. Contact your doctor if you experience new or unusual pain in your hip, groin or thigh.

High blood calcium levels after stopping treatment with Enwylma

Some patients with giant cell tumour of bone have developed high blood calcium levels weeks or months after stopping treatment. Your doctor will monitor you for signs and symptoms of high blood calcium levels after stopping treatment with Enwylma.

Children and adolescents

Enwylma is not recommended for children and adolescents under 18 years of age, except for adolescents with giant cell tumour of bone whose bones have stopped growing. The use of Enwylma has not been studied in children and adolescents with other types of cancer that have spread to the bones.

Other medicines and Enwylma

Tell your doctor or pharmacist if you are taking, have recently taken or might need to take any other medicines. This includes medicines obtained without a prescription. It is very important that you tell your doctor if you are being treated with

• another medicine containing denosumab
• a bisphosphonate

You should not take Enwylma together with other medicines containing denosumab or bisphosphonates.

Pregnancy and breastfeeding

Enwylma has not been studied in pregnant women. If you are pregnant, think you might be pregnant or are planning to become pregnant, consult your doctor before using this medicine. Enwylma is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment with Enwylma and for at least 5 months after stopping treatment with Enwylma.

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

It is unknown whether denosumab 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 discontinue denosumab, taking into account the benefits of breastfeeding for the child and the benefits of denosumab for the mother.

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

Talk to your doctor or pharmacist before taking any other medicine.

Driving and using machines

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

Enwylma contains sorbitol

This medicine contains 78 mg of sorbitol in each vial.

Enwylma contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 120 mg dose; this is essentially “sodium-free”.

Enwylma contains polysorbate 20 (E 432)

This medicine contains 0.17 mg of polysorbate 20 (E 432) in each vial, equivalent to 0.1 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Enwylma

Enwylma must be administered under the supervision of a healthcare professional.

The recommended dose of Enwylma is 120 mg given once every 4 weeks as a single subcutaneous injection (under the skin). Enwylma will be injected into the thigh, abdomen, or upper arm. If you are being treated for giant cell tumor of bone, you will receive an additional dose 1 and 2 weeks after the first dose.

Do not shake.

You should also take calcium and vitamin D supplements during treatment with Enwylma unless you have excess calcium in your blood. Your doctor will explain this to you.

If you have any further questions about the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Tell your doctor immediately if you experience any of the following symptoms during treatment with Enwylma (may affect more than 1 in 10 people):

• muscle spasms, tics, cramps, numbness or tingling in the fingers and toes or around the mouth and/or seizures, confusion or loss of consciousness. These symptoms may be a sign that your blood calcium levels are low. Low blood calcium may also cause a change in heart rhythm called QT prolongation, which is seen on an electrocardiogram (ECG).

Tell your doctor and dentist immediately if you experience any of the following symptoms during treatment with Enwylma or after stopping treatment (may affect up to 1 in 10 people):

• persistent pain in the mouth and/or jaw, swelling and/or non-healing ulcers in the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or loosening of a tooth, which may be signs of bone damage in the jaw (osteonecrosis).

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

• bone, joint and/or muscle pain, sometimes severe,
• breathing difficulties,
• diarrhoea.

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

• low blood phosphate levels (hypophosphataemia),
• dental extraction,
• excessive sweating,
• in patients with advanced cancer: development of another type of cancer.

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

• high blood calcium levels (hypercalcaemia) after stopping treatment in patients with giant cell tumour of bone,
• new or unusual pain in the hip, groin or thigh (may be an early sign of a possible fracture of the thigh bone),
• skin rash or mouth ulcers (drug-induced lichenoid eruptions).

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

• allergic reactions (for example: wheezing or breathing difficulties; swelling of the face, lips, tongue, throat or other body parts; skin rash, itching or hives). In rare cases, allergic reactions could be severe.

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 Enwylma

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

Do not use this medicine after the expiry date stated on the carton and label 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 vial in the outer packaging to protect it from light.

Before injection, the vial may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) to make the injection less uncomfortable. Once the vial has reached room temperature (up to 25 °C), it must be used within 30 days.

Medicines should 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 Enwylma

• The active substance is denosumab. Each vial contains 120 mg of denosumab in 1.7 ml of solution (equivalent to 70 mg/ml).
• The other components are glacial acetic acid, sodium hydroxide, sorbitol (E 420), polysorbate 20 and water for injections.

Appearance of the product and contents of the pack

Enwylma is an injectable solution.

Enwylma is a clear, colourless to slightly yellow solution, which may contain residual amounts of transparent to white particles.

Each pack contains one single-use vial.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Zentiva k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

Manufacturer

GH GENHELIX S.A.

Parque Tecnológico de León

Edificio GENHELIX

C/Julia Morros, s/n

Armunia 24009

León

Spain

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review 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.euopa.eu.

This information is intended for healthcare professionals only:

• Enwylma solution should be visually inspected before administration. The solution may contain residual amounts of protein particles ranging from translucent to white. Do not inject the solution if it is cloudy, shows a change in color, or contains numerous particles or foreign material.
• Do not shake.
• To avoid discomfort at the injection site, allow the vial to reach room temperature (up to 25 °C) before injection, and administer the injection slowly.
• The entire contents of the vial must be injected.
• For denosumab administration, a 27 G needle is recommended.
• Do not reinsert the needle into the vial.

Any unused medicinal product and materials that have come into contact with it must be disposed of in accordance with local regulations.