Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Obodence 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 of this leaflet includes information on how to report side effects.

Read this entire leaflet carefully before 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, ask 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, since it could 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 Obodence.

Contents of this leaflet

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

1. What Obodence is and what it is used for

What Obodence is and how it works

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

Bone is living tissue that is constantly being renewed. Oestrogens contribute to maintaining bone health. After menopause, oestrogen 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 can also occur in patients receiving glucocorticoid treatment. 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 prostate or breast cancer, can also cause bone loss. As a result, bones become weaker and more prone to breaking.

What Obodence is used for

Obodence is used to treat:

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

2. What you need to know before using Obodence

Do not use Obodence

if you have low levels of calcium in your blood (hypocalcemia).
if you are allergic to denosumab or 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 Obodence.

During treatment with Obodence, you may develop a skin infection with symptoms such as a swollen and red area on the 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 Obodence. Your doctor will discuss this with you.

While receiving Obodence, 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 calcium levels in the blood 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 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 you do not take calcium supplements.

Problems with mouth, teeth or jaw

In patients receiving Obodence 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 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 it has been a long time since your last dental check-up.
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 Obodence.

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 being treated with Obodence.

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 discharging ulcers, 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

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

Other medicines and Obodence

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 Obodence 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 might be pregnant, or plan to become pregnant. Obodence is not recommended during pregnancy. Women of childbearing potential must use effective contraception during treatment with Obodence and for at least 5 months after stopping treatment with Obodence.

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

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

Consult your doctor or pharmacist before using any other medicine.

Driving and using machines

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

Sorbitol (E 420)

This medicine contains 44 mg of sorbitol (E 420) per ml of solution.

Sodium

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

3. How to use Obodence

The recommended dose is one pre-filled syringe containing 60 mg 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 assists you) is giving the injection, they may also administer it into the outer side of the upper arm. Please consult your doctor about the date of your next possible injection.

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

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

Do not shake.

If you forget to use Obodence

If you miss a dose of Obodence, 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 Obodence

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

4. Possible adverse effects

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

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

Rarely, patients receiving Obodence may develop mouth and/or jaw pain, 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 your dentist immediately if you experience such symptoms while being treated with Obodence or after stopping treatment.

Rarely, patients receiving Obodence 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 Obodence. 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 Obodence. 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 being treated with Obodence.

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

bone, joint, and/or muscle pain, which may sometimes be severe,
leg or arm pain (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., purplish 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 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 listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Obodence

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 CAD/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 less uncomfortable.

Once the syringe has reached room temperature (up to 25 °C), it may be stored at room temperature for a single period of up to 60 days, without exceeding the original expiry date. If it is not used within this 60-day period, the syringe may be returned to the refrigerator and stored for up to 28 days for future use. Do not use the syringe after the expiry date printed on the label.

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 Obodence

The active substance is denosumab. Each 1 ml pre-filled syringe contains 60 mg of denosumab (60 mg/mL).
The other components are histidine, histidine monohydrochloride monohydrate, sorbitol (E 420), polysorbate 20, water for injections.

Appearance of the product and contents of the pack

Obodence is a clear, colourless to slightly yellowish injectable solution, supplied in a ready-to-use pre-filled syringe.

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

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

Instructions for use:

Component Guide
Before use	After use

Important

Read this important information before using the Obodence pre-filled syringe with needle guard:

It is important that you do not attempt to administer the injection yourself unless you have been trained by your doctor or healthcare professional.

Obodence is administered as an injection into the tissue just beneath the skin (subcutaneous injection).

Do not remove the needle cap from the pre-filled syringe until you are ready to inject.

Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare professional.

Do not attempt to activate the pre-filled syringe before the injection.

Do not attempt to remove the clear safety guard from the pre-filled syringe.

If you have any doubts, contact your doctor or healthcare professional.

Step 1: Preparation

Hold the safety shield of the pre-filled syringe to remove the pre-filled syringe from its packaging, and gather the materials you will need for your injection: alcohol wipes, cotton balls or gauze, a bandage, and a sharps disposal container (not included).

A hand holding a syringe with two black arrows indicating to press with fingers on the body of the device to push the piston

For safety:

Do not grasp by the plunger.
Do not grasp by the needle cap.

To minimize discomfort during injection, allow the pre-filled syringe to reach room temperature for about 30 minutes before injecting. Wash your hands thoroughly with soap and water.

Place the new pre-filled syringe and other materials on a clean, well-lit surface.

Do not attempt to heat the syringe using a heat source such as hot water or a microwave.
Do not leave the pre-filled syringe exposed to direct sunlight.
Do not shake the pre-filled syringe.
Keep the pre-filled syringe out of sight and reach of children.

Inspect the medication and the prefilled syringe.

Technical diagram of a medical device with a transparent container holding the medication indicated by a labeled line 'Medication'

Do not use the prefilled syringe if:

The medication is cloudy or contains particles. It should be a clear, colorless to slightly yellow solution.
Any of the components are cracked or broken.
The needle cap is missing or loose.
The expiration date printed on the label has passed (the last day of the month indicated).

In any of these cases, contact your doctor or healthcare professional.

Step 2: Prepare

Wash your hands thoroughly. Prepare and clean the injection site.

Diagram of the human body with gray areas indicating the upper arm

You can inject the medication in:

The upper thigh.
The abdomen, except for an area of 5 cm around the navel.
The outer side of the upper arm (only if administered by someone else).

Clean the injection site with an alcohol swab. Allow the skin to dry.

Do not touch the injection site before injecting.

Warning symbol with an exclamation mark next to Spanish text advising not to inject in areas with sensitive skin or scars

B	Carefully pull the needle cap straight off, keeping the syringe away from your body.

Pinch the injection site to create a firm surface.

Line drawing of a human torso where two hands pinch the skin of the

It is important to keep the skin pinched when injecting.

Step 3: Inject

Keep the skin pinched. INSERT the needle into the skin.

A hand holds a syringe vertically while the

Do not touch the clean area of the skin.

PRESS the plunger head with a gentle, constant pressure until you feel or hear a "click." Push fully downward until you hear the "click."

Two hands holding a medical device for the

Warning symbol composed of a black exclamation mark inside a triangle It is important to press down until you hear the "click" to receive your full dose.

STOP PUSHING the plunger head. Then, REMOVE the syringe from the skin.

A hand holds the top part of a medical device while the other

After releasing the plunger head, the safety shield of the prefilled syringe will securely cover the needle.

Do not recap the needle on used prefilled syringes.

Step 4: Final

Dispose of the used pre-filled syringe and other materials in a sharps disposal container.

A hand holds a syringe with needle pointing downward to insert it into a biohazard waste container with biohazard symbol

Medicines must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer need. This will help protect the environment.

Keep the syringe and sharps disposal container out of sight and reach of children.

Do not reuse the pre-filled syringe.
Do not recycle pre-filled syringes or throw them in the household waste.

B	Examine the injection site.
If you see blood, press the injection site with a cotton ball or gauze. Do not rub the injection site. If necessary, apply a bandage.