Izamby

Patient Information Leaflet: Information for the User

Izamby 60 mg solution for injection in pre-filled syringe

denosumab
This medicinal product is subject to additional monitoring. This will allow any new safety information to be identified quickly. 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 using this medicine as it contains important information for you.

• Keep this leaflet. 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 other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information that you need to know before and during treatment with Izamby.

Contents of this leaflet

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

1. What Izamby is and what it is used for

What Izamby is and how it works
Izamby contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, for the treatment of bone loss and osteoporosis. Treatment with denosumab 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, the reduction in 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 for various reasons, including ageing and/or low levels of the male hormone testosterone. It may 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 oestrogen 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 what type of treatment is Izamby used
Izamby 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 Izamby

Do not use Izamby

• 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 Izamby.
While being treated with Izamby, 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 accompanied by fever. Inform your doctor immediately if you experience any of these symptoms.
While being treated with Izamby, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
While being treated with Izamby, 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.
In rare cases, severely low levels of calcium in the blood have been reported, leading to hospitalization and even life-threatening reactions. Therefore, your blood calcium levels will be monitored (through blood tests) before each dose and, in patients at risk of developing hypocalcemia, within two weeks after the initial dose.
Inform your doctor if you currently have or have ever had severe kidney problems, impaired kidney function, or if you are undergoing dialysis, or if you are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), as these may increase your risk of low blood calcium levels if you do not take calcium supplements.

Problems with mouth, teeth or jaw
A side effect called osteonecrosis of the jaw (severe deterioration of the jaw bone tissue) has been reported rarely (may occur in up to 1 in 1,000 patients) in patients receiving denosumab for osteoporosis. The risk of osteonecrosis of the jaw increases in patients treated for a long period (may occur in up to 1 in 200 patients treated for 10 years). Osteonecrosis of the jaw can also occur after stopping treatment. It is important to try to prevent the development of osteonecrosis of the jaw, as it is a painful condition that can be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, take the following precautions:
Before receiving treatment, inform your doctor or nurse (healthcare provider) 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 Izamby.
During treatment, it is necessary to maintain good oral hygiene and undergo regular dental check-ups. If you wear dentures, ensure they are properly fitted. If you are currently undergoing dental treatment or are scheduled for dental surgery (e.g., tooth extractions), inform your doctor about the dental treatment and inform your dentist that you are being treated with Izamby.
Contact your doctor and dentist immediately if you notice any new problems with your mouth or teeth, such as tooth loss, pain or swelling, or failure of mouth sores to heal, or presence of discharge, as these could be signs of a side effect called osteonecrosis of the jaw (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
Izamby must not be used in children and adolescents under 18 years of age.

Other medicines and Izamby
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform your doctor if you are taking other medicines containing denosumab.
You must not take Izamby together with other medicines containing denosumab.

Pregnancy and breastfeeding
Izamby has not been studied in pregnant women. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor for advice before taking this medicine. The use of Izamby is not recommended during pregnancy. Women of childbearing potential must use effective contraceptive methods while taking Izamby and for at least 5 months after stopping treatment with Izamby.
If you become pregnant during treatment with Izamby or within 5 months after stopping treatment with Izamby, inform your doctor.
It is not known whether Izamby 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 discontinue breastfeeding or the use of Izamby, taking into account the benefit of breastfeeding for the child and the benefit of Izamby for the mother.
If you are breastfeeding during treatment with Izamby, inform your doctor.
Ask your doctor or pharmacist for advice before taking any medicine.

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

Izamby contains sorbitol
This medicine contains 46 mg of sorbitol per mL of solution.

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

Izamby 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 known allergies.

3. How to use Izamby

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor.
The recommended dose is one pre-filled syringe containing 60 mg administered once every 6 months,
as a single injection under the skin (subcutaneous). The most suitable injection sites are the upper
thighs and the abdomen. If someone assists you with the injection, the upper outer area of the arm may
also be used. Consult your doctor regarding the date of your next possible injection.
Each pack of Izamby contains a reminder card, which can be used to keep track of the date of your next
injection.
During treatment with Izamby, you must also take calcium and vitamin D supplements. Your doctor will
discuss this with you.
Your doctor will decide whether it is better for you or for the person assisting you to administer the
Izamby injection. Your doctor or nursing staff will show you or the person assisting you how to use
Izamby. For instructions on how to inject Izamby, please refer to the section at the end of this leaflet.
Do not shake.
Before administration, the solution should be inspected. Do not inject the solution if it contains
particles, or if it appears cloudy or discoloured.
If you forget to use Izamby
If you have missed a dose of Izamby, 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 Izamby
To obtain the maximum benefit from treatment in reducing the risk of fractures, it is important to use
Izamby 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 everyone will experience them.

Uncommonly, patients treated with Izamby may develop skin infections (especially cellulitis). Contact your doctor immediately if you experience any of the following symptoms while taking Izamby: redness and swelling of the skin, most commonly in the lower leg, accompanied by warmth, pain, and possibly fever.

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

Rarely, patients treated with Izamby may develop low levels of calcium in the blood (hypocalcemia). Severe hypocalcemia may require hospitalization and can be life-threatening. Symptoms include 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. Contact your doctor immediately if you experience any of these symptoms. Low calcium levels 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 Izamby. Contact your doctor if you develop 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 treated with Izamby. Symptoms include swelling of the face, lips, tongue, throat, or other parts of the body; rash, itching, hives, wheezing, or difficulty breathing. Contact your doctor if you experience any of these symptoms during treatment with Izamby.

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

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

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

• frequent and painful urination, blood in the 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 discomfort (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 in 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):

• contact your doctor if you experience ear pain, ear discharge, and/or an ear infection. These may 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 referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Izamby

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and on the carton after
Exp/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 pre-filled syringe 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 must be used within 30 days.
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 Izamby contains

• 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.

Description of the appearance of Izamby and contents of the pack
Izamby is an injectable solution, from colourless to slightly yellow, supplied in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with needle protection.

Marketing Authorisation Holder
Mabxience Research SL
C/ Manuel Pombo Angulo 28
28050 Madrid
Spain

Manufacturer
GH GENHELIX S.A.
Parque Tecnológico de León
Edificio GENHELIX
C/Julia Morros, s/n
Armunia, 24009 León, Spain

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

België/Belgique/Belgien Lietuva
Mabxience Research SL UAB EGIS Lithuania
Tél/Tel: + 34 917 711 500 Tel: + 370 5 231 4658

България Luxembourg/Luxemburg
EGIS Bulgaria Mabxience Research SL
Teл.: + 359 2 987 60 40 Tél/Tel: + 34 917 711 500

Česká republika Magyarország
EGIS Praha, spol. s r.o Egis Gyógyszergyár Zrt.
Tel: + 420 227 129 111 Tel.: + 36 1 803 5555

Danmark Malta
Medical Valley Invest AB Mabxience Research SL
Tlf: + 46 40 122131 Tel: + 34 917 711 500

Deutschland Nederland
Mabxience Research SL Medical Valley Invest AB
Tel: + 34 917 711 500 Tel: + 46 40 122131

Eesti Norge
Mabxience Research SL Medical Valley Invest AB
Tel: + 34 917 711 500 Tlf: + 46 40 122131

Ελλάδα Österreich
ELPEN Pharmaceutical Co. Inc Gebro Pharma GmbH
Τel: + 30 210 6039326-9 Tel: + 43 (0)5453 5300-0

España Polska
Laboratorios Gebro Pharma S.A Egis Polska sp. z o.o.
Tel: + 34 93 205 86 86 Tel.: + 48 22 417 92 00

France Portugal
Laboratoires Biogaran Mabxience Research SL
Tél: + 33 (0) 800 970 109 Tel: + 34 917 711 500

Hrvatska România
Mabxience Research SL Egis Rompharma SRL
Tel: + 34 917 711 500 Tel: + 40 21 412 00 17

Ireland Slovenija
Mabxience Research SL Mabxience Research SL
Tel: + 34 917 711 500 Tel: + 34 917 711 500

Ísland Slovenská republika
Mabxience Research SL EGIS SLOVAKIA spol. s r.o.,
Sími: + 34 917 711 500 Tel: + 421 2 3240 9422

Italia Suomi/Finland
Abiogen Pharma S.p.A Medical Valley Invest AB
Tel: + 39 050 315 4101 Puh/Tel: + 46 40 122131

Κύπρος Sverige
Mabxience Research SL Medical Valley Invest AB
Τηλ: + 34 917 711 500 Tel: + 46 40 122131

Latvija
Egis Latvia SIA
Tel: + 371 676 13859

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

Instructions for use

Read these instructions before starting to use the pre-filled syringes of Izamby with needle protection, and each time you receive a new package. There may be new information. You should also consult your healthcare provider regarding your medical condition or treatment.
Keep these Instructions for use so you can refer to them again if necessary.
IMPORTANT INFORMATION
Important information to know before administering the Izamby injection:

• It is important that you do not attempt to perform the injection unless you have received adequate instructions from your doctor or healthcare provider on the correct way to inject Izamby.
• Izamby is administered only as a subcutaneous injection (an injection directly under the skin).
• Do not open the outer packaging until it is time to use this medicine.
• Do not remove the needle cap from the pre-filled syringe until you are ready for the injection.
• Do not use the pre-filled syringe if it has fallen on a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare provider.
• Do not attempt to activate the pre-filled syringe before the injection.
• Do not attempt to remove the needle protection from the pre-filled syringe.

Contact your doctor or healthcare provider if you or the person assisting you has any questions about the correct way to inject Izamby.
Figure 1 shows what the pre-filled syringe with needle protection looks like before (a) and after (b) use.

Figure 1

1. Preparation for Izamby Injection

Gather the materials

• On a clean, well-lit work surface, gather the materials needed for the injection:
  o Izamby package with prefilled syringe
  o Alcohol swabs
  o Cotton ball or gauze
  o Adhesive bandage
  o Sharps disposal container

Allow to reach room temperature

• For a more comfortable injection, let the prefilled syringe package remain at room temperature for approximately 30 minutes before injection ( Figure A ).
  o Do not attempt to warm the prefilled syringe using a heat source such as hot water or microwave.
  o Do not expose the prefilled syringe to direct sunlight.
  o Do not shake the prefilled syringe.
  o Keep the prefilled syringe out of sight and reach of children.

Figure A
Wash your hands

• Wash your hands thoroughly with soap and water ( Figure B ).

Figure B
Remove the prefilled syringe from the package

• Open the package.
• Hold the prefilled syringe by the barrel ( Figure C ).
• Lift the syringe out of the package.
• Place the syringe on a clean, flat work surface. For safety:
  o Do not touch the plunger.
  o Do not touch the needle cap.

Figure C
Inspect the medicine and prefilled syringe

• Check that the name “Izamby” is printed on the label ( Figure D ).
• Check the expiration date printed on the label ( Figure D ).
• Check that the medicine is a clear, colorless to slightly yellow solution ( Figure D ).
• Check whether the prefilled syringe is damaged.

Do not use the prefilled syringe if:

• The solution is cloudy or contains particles.
• Any parts appear cracked or broken.
• The needle cap is missing or not securely attached.
• The expiration date printed on the label has passed the last day of the month indicated.

If any of the above conditions apply, contact your doctor or healthcare provider.

Figure D

2. Preparation

Prepare the injection site

• Choose the injection site (Figure E): You may use:
  • The upper part of the thigh.
  • The abdomen, except for an area within 5 centimeters around the navel.
  • The outer upper part of the arm (only if someone else is administering the injection to you).
• Do not inject into areas where the skin is tender, bruised, red, or hardened. Avoid injecting into areas with scars or stretch marks.

Figure E
Clean the injection site

• Clean the injection site with an alcohol swab (Figure F).
• Allow the skin to dry.
• Do not touch the injection site before injecting.

Figure F
Remove the needle cap

• Carefully remove the needle cap by pulling it straight off, away from your body (Figure G).
• Discard the needle cap.
• Do not attempt to re-cap the needle.

Figure G

3. Izamby Injection

Insert the needle

• Lift the injection site to create a stable surface (Figure H).
• Do not touch the cleaned area of skin. Note: It is important to keep the skin lifted during injection.
• Insert the needle at a 45-90 degree angle into the lifted skin (Figure I).

Figure H

Figure I
Izamby Injection

• Slowly and completely push the plunger until all the liquid has been injected and the syringe is empty (Figure J).

Note: The plunger must be fully depressed to ensure the full dose has been administered and to activate the needle safety guard.

Figure J
Release the thumb

• Release your thumb from the plunger to allow the needle safety guard to cover the needle (Figure K).
• Then remove the syringe from the skin (Figure L).
• Release the lifted skin.

Contact your doctor or healthcare professional immediately if:

• You did not inject the full dose, or
• The needle safety guard does not activate after injection.

Figure K

Figure L

1. Disposal of Izamby

Dispose of the syringe

• Place the used pre-filled syringe and other materials into a sharps disposal container ( Figure M ). Note: Medicines must be disposed of in accordance with local regulations. Ask your doctor or healthcare provider how to dispose of medicines you no longer use. This will help protect the environment.
• Do not replace the needle cap on used pre-filled syringes.
• Do not reuse the pre-filled syringe, even if not all of the medicine was injected.
• Do not recycle pre-filled syringes or dispose of them in household waste.
• Keep the syringe and the sharps disposal container out of sight and reach of children.

Figure M
Examine the injection site

• If you see blood, press a cotton ball or gauze pad against the injection site.
• Do not rub the injection site. A bandage may be applied if needed.

Record the date of your next injection

• Record the date of your next injection on the reminder card included in the package ( Figure N ).

Figure N