Obodence

Patient Information Leaflet

Obodence 60 mg solution for injection in pre-filled syringe

denosumab
▼This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information that you must know before and during treatment with Obodence.

Contents of this leaflet

1. What Obodence is and what it is used for
2. What you need to know before using Obodence
3. How to use Obodence
4. Possible side effects
5. How to store Obodence
6. 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, for the treatment of bone loss and osteoporosis. Treatment with Obodence makes bones stronger and less prone to fractures.
Bone is a living tissue that is constantly being renewed. Oestrogens help maintain healthy bones. After menopause, reduced oestrogen levels can make bones thin and fragile, which may lead to the development of a condition called osteoporosis. Osteoporosis can also occur in men due to various causes, including ageing and/or low levels of the male hormone testosterone. It can also occur in patients receiving glucocorticoids. Many patients with osteoporosis do not have symptoms, but are still at risk of bone fractures, especially in the spine, hip, and wrists.
Surgical procedures or medications that suppress the production of oestrogens or testosterone, used in the treatment of patients with breast or prostate cancer, can also cause bone loss. As a result, bones become more fragile and more likely to fracture.

For which types of treatment is Obodence used?
Obodence is used for the treatment of:

• osteoporosis in postmenopausal women (postmenopausal osteoporosis) and in men who have an increased risk of fractures (broken bones), to reduce the risk of vertebral, non-vertebral, and hip fractures;
• bone loss in men resulting from reduced hormone levels (testosterone) due to surgery or pharmacological therapy in patients with prostate cancer;
• bone loss due to long-term treatment with glucocorticoids in patients at increased 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 to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before using Obodence.
While being treated with Obodence, you may develop a skin infection with symptoms such as swelling,
redness, most commonly in the lower leg, with a feeling of warmth and pain (cellulitis), possibly with
fever. Inform your doctor immediately if you experience any of these symptoms.
While being treated with Obodence, you must also take calcium and vitamin D supplements. Your doctor
will discuss this with you.
While being treated with Obodence, you may have low levels of calcium in your blood. Inform your
doctor immediately if you notice any of the following symptoms: 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.
Inform your doctor if you have or have ever had severe kidney problems, kidney impairment, if you are
on dialysis, or if you are taking medicines called glucocorticoids (such as prednisolone or dexamethasone),
which may increase your risk of low calcium levels in the blood if you do not take calcium supplements.

Problems with mouth, teeth or jaw
A side effect called osteonecrosis of the jaw/mandible (serious deterioration of the jaw/mandible bone
tissue) has been reported rarely (may occur in up to 1 in 1,000 patients) in patients receiving Obodence
for osteoporosis. The risk of osteonecrosis of the jaw/mandible increases in patients treated for a long
period (may occur in up to 1 in 200 patients if treated for 10 years). Osteonecrosis of the jaw/mandible
may also occur after stopping treatment. It is important to try to prevent the development of osteonecrosis
of the jaw/mandible, as it is a painful condition that may be difficult to treat. To reduce the risk of
developing osteonecrosis of the jaw/mandible, take the following 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 hygiene, gum disorders, or if you are scheduled for a tooth extraction;
• do not regularly receive dental care or have not had a dental check-up for a long time;
• are a smoker (as this may increase the risk of dental problems);
• have previously been treated with a bisphosphonate (used to treat or prevent bone disorders);
• are taking medicines called corticosteroids (such as prednisolone or dexamethasone);
• have cancer.

Your doctor may ask you to have a dental examination (by a dentist) before starting treatment with
Obodence.
During treatment, it is necessary to maintain good oral hygiene and to have regular dental check-ups. If
you wear dentures, make sure they fit properly. If you are currently undergoing dental treatment or are
planning to have dental surgery (e.g. tooth extractions), inform your doctor about the dental treatment
and inform your dentist that you are being treated with Obodence.
Contact your doctor and dentist immediately if you notice any problems with your mouth or teeth such
as tooth loss, pain or swelling, or failure of mouth sores to heal, or if you have discharge, as these may
be signs of a side effect called osteonecrosis of the jaw/mandible (ONJ).

Atypical femoral fractures
Some people have developed atypical fractures of the femur during treatment with denosumab.
Contact your doctor if you experience new or unusual pain in your hip, groin or thigh.

Children and adolescents
Obodence must not be used in children and adolescents under 18 years of age.

Other medicines and Obodence
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
It is particularly important that you inform your doctor if you are taking other medicines containing
denosumab.
You must not take Obodence together with other medicines 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 are planning to become pregnant. The use of Obodence is not
recommended during pregnancy. Women of childbearing potential must use effective contraception while
taking 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, please inform your doctor.
It is not known whether denosumab passes into breast milk. It is important that you inform your doctor
if you are breastfeeding or planning to breastfeed. Your doctor will then help you decide whether to stop
breastfeeding or stop taking Obodence, taking into account the benefits of breastfeeding for the child and
the benefits of taking Obodence for the mother.
If you are breastfeeding during treatment with Obodence, please inform your doctor.
Ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines
Obodence has no effect or has a negligible effect on the ability to drive and use machines.

Sorbitol (E420)
This medicine contains 44 mg of sorbitol (E420) per mL of solution.

Sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 60 mg, i.e. essentially ‘sodium-free’.

3. How to use Obodence

The recommended dose is one pre-filled 60 mg syringe administered once every 6 months as a single subcutaneous injection. The most suitable injection sites are the upper thighs and the abdomen. If an assistant is giving the injection, the upper outer area of the arm may also be used. Consult your doctor regarding the timing of your next possible injection.
During treatment with Obodence, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
Your doctor will decide whether it is preferable for you or for your assistant to administer the Obodence injection. Your doctor or nursing staff will show you or your assistant how to administer Obodence. For instructions on how to inject Obodence, please refer to the section at the end of this leaflet.
Do not shake.
If you forget to take Obodence
If you have missed a dose of Obodence, the injection should be given as soon as possible.
Afterwards, injections should be given every 6 months from the date of the last injection.
If you stop using Obodence
To obtain the maximum benefit from treatment in reducing the risk of fractures, it is important to take Obodence for the entire duration prescribed by your doctor. Do not stop treatment without consulting your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Infections of the skin (especially cellulitis) may occur uncommonly in patients treated with Obodence. Contact your doctor immediately if you experience any of the following symptoms while taking Obodence: skin redness and swelling, most commonly in the lower leg, with a feeling of warmth and pain, possibly accompanied by fever.

Rarely, patients treated with Obodence may develop pain in the mouth and/or jaw, swelling or non-healing lesions in the mouth or jaw, discharge, numbness or a sensation of heaviness in the jaw, or loose teeth. These could be signs of a serious deterioration of the bone tissue in the jaw (osteonecrosis). Contact your doctor and dentist immediately if you experience such symptoms during or after treatment with Obodence.

Rarely, patients treated with Obodence may develop low levels of calcium in the blood (hypocalcaemia). 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. Contact your doctor immediately if any of these symptoms occur. Low calcium levels in the blood may also lead to changes in heart rhythm known as QT interval prolongation, which can be detected by an electrocardiogram (ECG).

Rarely, atypical femoral fractures may occur in patients treated with Obodence. Contact your doctor if you develop new or unusual pain in the hip, groin or thigh, as this could be an early sign of a possible femoral fracture.

Rarely, allergic reactions may occur in patients treated with Obodence. Symptoms include swelling of the face, lips, tongue, throat or other body parts; skin rash, itching, hives, wheezing or difficulty breathing. Please contact your doctor if you experience any of these symptoms during treatment with Obodence.

Very common side effects (may occur in more than 1 in 10 people):

• bone, joint and/or muscle pain, sometimes severe,
• pain in arms or legs (limb pain).

Common side effects (may occur in up to 1 in 10 people):

• frequent and painful urination, blood in urine, urinary incontinence,
• upper respiratory tract infections,
• pain, tingling or numbness radiating to the lower limbs (sciatica),
• constipation,
• abdominal discomfort,
• skin rash,
• itching, redness and/or dryness of the skin (eczema),
• hair loss (alopecia).

Uncommon side effects (may occur in up to 1 in 100 people):

• fever, vomiting and abdominal pain or abdominal disorders (diverticulitis),
• ear infections,
• skin rash or mouth ulcers (drug-induced lichenoid eruptions).

Very rare side effects (may occur in up to 1 in 10,000 people):

• allergic reaction that may damage blood vessels, mainly affecting the skin (e.g. purple or red-brown spots, hives or skin ulcers) (hypersensitivity vasculitis).

Not known (frequency cannot be estimated from the available data):

• inform your doctor if you experience ear pain, ear discharge, and/or ear infection. These could be signs of damage to the ear bone.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the container in the outer packaging to protect the medicine from light.
The pre-filled syringe may be removed from the refrigerator and allowed to reach room temperature (up to 25°C) before injection. This will make the injection more comfortable.
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, but not beyond the original expiry date. If it is not used within this maximum period of 60 days, the syringe may be returned to the refrigerator for up to 3 days for future use. Do not reuse the syringe after the expiry date stated on the label.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Obodence contains

• The active substance is denosumab. Each 1 mL pre-filled syringe contains 60 mg of denosumab (60 mg/mL).
• The other components are histidine, monohydrochloride monohydrate of histidine, sorbitol (E420), polysorbate 20, water for injections.

Description of the appearance of Obodence and contents of the pack
Obodence is a clear, colourless to slightly yellow, injectable solution in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with needle protection.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Instructions for use:

Guide to the parts
Before use	After use
Plunger Base for fingers Syringe label Syringe barrel Needle safety shield Safety spring of the needle Needle cap inserted	Used plunger Used syringe label Used syringe barrel Used needle Used needle safety spring Removed needle cap

Important
Before using a pre-filled Obodence syringe with needle protection, read these important
information:

• It is important that you do not attempt to perform the injection unless you have received adequate instructions from 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 for injection.
• 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 transparent safety shield from the pre-filled syringe. Contact your doctor or healthcare professional for any questions.

Step 1: Preparation
A	Grasp the safety shield of the prefilled syringe to remove the prefilled syringe from its packaging and prepare the materials needed for the injection: alcohol swabs, a cotton ball or gauze, a bandage, and a sharps disposal container (not included).
Grasp here For safety reasons: •Do not grasp the plunger. •Do not grasp the needle cap.
For a more comfortable injection, allow the prefilled syringe to reach room temperature for approximately 30 minutes before injection. Wash your hands thoroughly with soap and water. Place the new prefilled syringe and other required materials on a clean, well-lit work surface. •Do not attempt to warm the syringe using a heat source such as hot water or a microwave. •Do not expose the prefilled syringe to direct sunlight. •Do not shake the prefilled syringe excessively. •Keep the prefilled syringe out of sight and reach of children.

B Check the medicine and the pre-filled syringe.

Medicine
Do not use the pre-filled syringe if:

• The medicine is cloudy or there are particles inside. It should be a clear, colourless to slightly yellow solution.
• Any parts appear cracked or broken.
• The needle cap is missing or not securely attached.
• The expiry date printed on the label has passed the last day of the month indicated. In all cases, contact your doctor or healthcare provider.

Step 2: Preparation
A	Wash your hands thoroughly. Prepare and clean the injection site.
You may use: Upper arm Abdomen Upper thigh •The upper thigh. •The abdomen, except for a 5-centimeter area directly around the navel. •The outer upper arm (only if someone else is administering the injection). Clean the injection site with an alcohol swab. Let the skin dry. •Do not touch the injection site before injecting. Do not inject in areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
B	Carefully remove the needle cap by pulling it straight off and away from the body.
C	Lift the injection site to create a stable surface.
It is important to keep the skin lifted during injection.
Step 3: Injection
A	Keep the skin lifted. INSERT the needle into the skin.
Do not touch the cleaned area of skin.

B PUSH the plunger slowly and steadily until you feel or hear a "click".
Push all the way to the "click".

"Click"

It is important to push all the way to the "click" to deliver the full dose.

C	RELEASE your thumb. Then WITHDRAW the syringe from the skin.
After releasing the plunger, the safety shield of the pre-filled syringe will automatically cover the injection needle securely. •Do not recap the needle on used pre-filled syringes.
Step 4: Completion
A	Dispose of the used pre-filled syringe and other materials in a sharps disposal container.
Medicines must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Keep the syringe and sharps disposal container out of the sight and reach of children. •Do not reuse the pre-filled syringe. •Do not recycle pre-filled syringes or dispose of them in household waste.
B	Examine the injection site.
If you see any bleeding, apply a cotton ball or gauze pad to the injection site. Do not rub the injection site. Apply a bandage if needed.