Acvybra 60 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Acvybra 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. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for information on how to report adverse reactions.

Read this 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. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.
• You will be provided with a patient reminder card containing important safety information you should know before and during your treatment with Acvybra.

Leaflet contents

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

1. What Acvybra is and what it is used for

What Acvybra is and how it works

Acvybra 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 a living tissue that is continuously 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 may also occur in patients receiving glucocorticoid therapy. Many patients with osteoporosis do not have symptoms, yet remain 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 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 Acvybra is used for

Acvybra is used to treat:

• osteoporosis in postmenopausal women and men who are at increased risk of fractures (broken bones), reducing the risk of vertebral, non-vertebral, and hip 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 at high risk of fracture.

2. What you need to know before using Acvybra

Do not use Acvybra:

• 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 Acvybra.

During treatment with denosumab, 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.

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

While receiving denosumab, you may develop low levels of calcium in the 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.

Rarely, cases of very low blood calcium levels have been reported, requiring hospitalization and, in some cases, 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 insufficiency, if you have required dialysis, or if you are taking medications called glucocorticoids (such as prednisolone or dexamethasone), as these may increase the 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, as it can be a painful condition that may be difficult to treat. To reduce the risk of developing ONJ, follow these precautions:

Before starting 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 medications called corticosteroids (such as prednisolone or dexamethasone).
• you have cancer.

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

During treatment with denosumab, 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 denosumab.

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 draining sores, as these could be symptoms of ONJ.

Unusual femur fractures

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

Children and adolescents

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

Other medicines and Acvybra

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 Acvybra together with another medicine containing denosumab.

Pregnancy and breastfeeding

Denosumab has not been studied in pregnant women. It is important to inform your doctor if you are pregnant, think you might be pregnant, or plan to become pregnant. Denosumab is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment with denosumab and for at least 5 months after stopping treatment with denosumab.

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

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

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

3. How to use Acvybra

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 thigh and the abdomen. If the injection is given by a caregiver (a person who assists you), the injection may also be administered into the outer side of the upper arm. Consult your doctor for the date of your next possible injection. Each denosumab 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 Acvybra. Your doctor will discuss this with you.

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

Do not shake.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, stating the medication and the amount ingested.

If you forget to use Acvybra

If you miss a dose of Acvybra, the injection should be given as soon as possible. After that, injections should be scheduled every 6 months starting from the date of the last injection.

If you stop treatment with Acvybra

To obtain the maximum benefit from your treatment and to reduce the risk of fractures, it is important that you use denosumab 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 denosumab may rarely develop skin infections (mainly cellulitis). Contact your doctor immediately if any of the following symptoms occur during treatment with denosumab: 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 denosumab 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 receiving denosumab treatment or after stopping treatment.

Rarely, patients receiving denosumab may develop low levels of calcium in the blood (hypocalcemia); very low calcium levels can require hospitalization and may 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 denosumab.

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 denosumab. Symptoms include swelling of the face, lips, tongue, throat, or other body parts; skin rash, itching, or hives; wheezing or difficulty breathing. Contact your doctor if you experience such symptoms while receiving Acvybra.

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

• bone, joint, and/or muscle pain, sometimes severe,
• pain in the 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, 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, talk to your doctor, pharmacist, or nurse, even if it is an 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 Acvybra

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the label and carton following "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 its outer packaging 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 any unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Acvybra

• The active substance is denosumab. Each 1 ml pre-filled syringe contains 60 mg of denosumab (60 mg/mL).
• The other components are L-histidine, L-histidine monohydrochloride monohydrate, sucrose, poloxamer 188, and water for injections.

Appearance of Acvybra and contents of the pack

Acvybra is a clear, colourless to slightly yellowish injectable solution available in a pre-filled syringe ready for use.

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

Marketing Authorization Holder

Reddy Holding GmbH
Kobelweg 95
86156 Augsburg
Germany

Manufacturer responsible for production

Alvotech hf
Sæmundargata 15-19
102 Reykjavik
Iceland

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

Date of the most recent review of this leaflet: 10/2025

Other sources of information

You can find detailed information about this medicine on the website of the European Medicines Agency: https://www.ema.europa.eu.