Kefdensis 60 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Kefdensis 60 mg solution for injection in pre-filled syringe

denosumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4 at the end 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, consult 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 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 reminder card containing important safety information you should know before and during your treatment with Kefdensis.

Leaflet contents

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

1. What Kefdensis is and what it is used for

What Kefdensis is and how it works

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

Bone is living tissue that is constantly renewed. Estrogens contribute to maintaining bone health. After menopause, estrogen levels decrease, 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 remain at risk of bone fractures, particularly in the spine, hip, and wrists.

Surgical procedures or medications that suppress estrogen or testosterone production, used to treat patients with prostate or breast cancer, can also cause bone loss. Bones become weaker and break more easily.

What Kefdensis is used for

Kefdensis is used to treat:

• postmenopausal osteoporosis in women and osteoporosis in men who are at increased risk of fracture, 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 are at high risk of fracture.

2. What you need to know before using Kefdensis

Do not use Kefdensis

• 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 treatment with Kefdensis.

While receiving Kefdensis, 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), and which may be accompanied by fever. Contact your doctor immediately if you experience any of these symptoms.

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

While receiving Kefdensis, you may develop low levels of calcium in the blood. Contact 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.

In rare cases, very low levels of calcium 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, within two weeks after the initial dose, your blood calcium levels will be checked (via 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 medications called glucocorticoids (such as prednisolone or dexamethasone), as these may increase your 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 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 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 a 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 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 Kefdensis.

During treatment, 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 receiving Kefdensis.

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 ulcers, as these could be symptoms of ONJ.

Unusual femur fractures

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

Children and adolescents

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

Other medicines and Kefdensis

Tell 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 Kefdensis together with another medicine containing denosumab.

Pregnancy and breastfeeding

Denosumab 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 plan to become pregnant. Kefdensis is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment with Kefdensis and for at least 5 months after stopping treatment with Kefdensis.

If you become pregnant during treatment with Kefdensis or within 5 months after stopping treatment with Kefdensis, 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 stop using Kefdensis, taking into account the benefits of breastfeeding for the child and the benefits of Kefdensis for the mother.

If you are breastfeeding during treatment with Kefdensis, 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 negligible or none.

3. How to use Kefdensis

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 sites for the injection are the upper thighs and the abdomen. Your caregiver may also administer the injection into the outer side of your upper arm. Consult your doctor for the date of your next possible injection. You will be given a reminder card, which can be used to keep a record of the date of your next injection.

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

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

Do not shake.

If you forget to use Kefdensis

If you miss a dose of Kefdensis, 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 Kefdensis

To get the maximum benefit from your treatment and to reduce the risk of fractures, it is important to use Kefdensis 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 may cause adverse effects, although not everyone experiences 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 Kefdensis: 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 heaviness sensation 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 on treatment with Kefdensis 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 femoral 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 femoral 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 these symptoms while on treatment with Kefdensis.

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

• bone, joint, and/or muscle pain, sometimes severe,
• pain in 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).

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 dark red 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 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 may also report them through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Kefdensis

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 on the carton after 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.

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 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 that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Kefdensis

• 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 Kefdensis and contents of the pack

Kefdensis is a clear, colorless to slightly yellowish injectable solution in a ready-to-use pre-filled syringe.

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

Marketing Authorization Holder

STADA Arzneimittel AG

Stadastrasse 2–18

61118 Bad Vilbel

Germany

Manufacturer

Alvotech hf

Sæmundargata 15-19

102 Reykjavik

Iceland

For further 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 medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/