Zadenvi 60 mg solution for injection in pre-filled syringe: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

ZADENVI 60 mg solution for injection in pre-filled syringe

denosumab

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

Read this entire 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, consult your doctor or pharmacist.
This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
If you experience any side effects, consult 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 alert card containing important safety information you should know before and during treatment with ZADENVI.

Leaflet Contents

What ZADENVI is and what it is used for
What you need to know before using ZADENVI
How to use ZADENVI
Possible side effects
How to store ZADENVI
Contents of the pack and other information

1. What ZADENVI is and what it is used for

What ZADENVI is and how it works

ZADENVI contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, aimed at treating bone loss and osteoporosis. Treatment with denosumab strengthens bones and reduces the risk of fractures.

Bone is living tissue that is constantly being renewed. Estrogens contribute to maintaining bone health. After menopause, estrogen 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 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 ZADENVI is used for

ZADENVI is used to treat:

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

2. What you need to know before using ZADENVI

Do not use ZADENVI

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 starting to use ZADENVI.

While being treated with ZADENVI, you may develop a skin infection with symptoms such as a red, swollen area of skin, most commonly on 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.

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

While receiving ZADENVI, you may develop low levels of calcium in the blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, twitches 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 levels of calcium in the blood have been reported, requiring hospitalization and, in some instances, leading to potentially life-threatening reactions. Therefore, before each dose is administered, and in patients predisposed to hypocalcemia, within two weeks after the initial dose, your blood calcium levels will be checked (through a blood test).

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 the risk of low blood calcium levels if calcium supplements are not taken.

Problems in the mouth, teeth or jaw

In patients receiving denosumab 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 the development of ONJ, 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 examination 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 ZADENVI.

During treatment, you should maintain good oral hygiene and undergo routine 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 ZADENVI.

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

Unusual femur fractures

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

Children and adolescents

ZADENVI must not be used in individuals under 18 years of age.

Other medicines and ZADENVI

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 ZADENVI together with another medicine containing denosumab.

Pregnancy and breastfeeding

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

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

It is unknown whether ZADENVI 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 ZADENVI, taking into account the benefit of breastfeeding for the child and the benefit of ZADENVI for the mother.

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

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

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

ZADENVI contains sorbitol

This medicine contains 46 mg of sorbitol in each ml of solution.

ZADENVI contains sodium

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

ZADENVI contains polysorbate

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

3. How to use ZADENVI

Follow exactly the instructions for administration of this medicine given by your doctor. If in doubt, consult your doctor again.

The recommended dose is one 60 mg pre-filled syringe administered under the skin (subcutaneous route) as a single injection every 6 months. The best places to give the injection are the upper thighs and the abdomen. If a caregiver (a person who cares for you) is administering the injection, it may also be given in the outer side of the upper arm. Consult your doctor about the date of the next possible injection. Each ZADENVI package contains a reminder card that can be used to keep a record of the date of the next injection.

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

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

Do not shake.

Before administration, the solution should be inspected. Do not inject the solution if it contains particles, is cloudy, or has changed in colour.

If you forget to use ZADENVI

If you miss a dose of ZADENVI, 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 ZADENVI

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

4. Possible adverse effects

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

Patients treated with ZADENVI may occasionally develop skin infections (mainly cellulitis). Inform your doctor immediately if any of the following symptoms occur during treatment with ZADENVI: a swollen and 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 ZADENVI 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). Inform your doctor and your dentist immediately if you experience such symptoms while being treated with ZADENVI or after stopping treatment.

Rarely, patients receiving ZADENVI may develop low levels of calcium in the blood (hypocalcaemia); 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, inform 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 ZADENVI. 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 ZADENVI. Symptoms include swelling of the face, lips, tongue, throat, or other parts of the body; skin rash, itching, or hives; wheezing or difficulty breathing. Inform your doctor if you experience such symptoms while being treated with ZADENVI.

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, discharge from the ear, 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 included in Appendix V.* By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of ZADENVI

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.

Prior to 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 no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of ZADENVI

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.

Appearance of the product and contents of the pack

ZADENVI is an injectable solution, colourless to slightly yellow, available in a pre-filled syringe ready for use.

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

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

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

Belgium/Belgium/Belgium

Zentiva, k.s.

Tel/Tel: +32 (78) 700 112