BORTEZOMIB SUN 3.5 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bortezomib SUN 3.5 mg powder for solution for injection EFG

bortezomib

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Bortezomib SUN is and what it is used for

Bortezomib SUN contains the active substance bortezomib, a "proteasome inhibitor". Proteasomes play a critical role in controlling cell function and growth. Bortezomib can destroy cancer cells by interfering with their function.

Bortezomib SUN is used for the treatment of:

• multiple myeloma(a type of bone marrow cancer) in patients over 18 years of age:
• alone or with the medicines liposomal doxorubicin or dexamethasone, for patients whose disease is getting worse (in progression) after receiving at least one previous treatment and for those patients whose blood stem cell transplant did not work or is not suitable.
• in combination with the medicines melphalan and prednisone, for patients who have not received previous treatment and are not suitable for high-dose chemotherapy before a blood stem cell transplant.
• in combination with the medicines dexamethasone or dexamethasone plus thalidomide, in patients who have not received previous treatment and are receiving high-dose chemotherapy before a blood stem cell transplant (induction treatment).
• mantle cell lymphoma(a type of cancer that affects the lymph nodes) in patients 18 years or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not received previous treatment and for those patients who are not considered suitable for a blood stem cell transplant.

2. What you need to know before you use Bortezomib SUN

Do not use Bortezomib SUN

• if you are allergic to bortezomib, boron, or any of the other ingredients of this medicine (listed in section 6)
• if you have certain severe lung or heart problems.

Warnings and precautions

Tell your doctor if you have:

• low red blood cell or white blood cell count
• bleeding problems and/or low platelet count in the blood
• diarrhea, constipation, nausea, or vomiting
• a history of fainting, dizziness, or lightheadedness
• kidney problems
• moderate to severe liver problems
• numbness, tingling, or pain in the hands or feet (neuropathy) in the past
• heart problems or high blood pressure
• difficulty breathing or coughing
• seizures
• shingles (localized, including around the eyes, or widespread)
• symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss, or difficulty breathing
• memory loss, thought disturbances, difficulty walking, or vision loss. These may be signs of a serious brain infection, and your doctor may advise further tests and monitoring.

You will need to have regular blood tests before and during treatment with Bortezomib SUN to check your blood cell count regularly.

You must inform your doctor if you have mantle cell lymphoma and are given rituximab together with Bortezomib SUN:

Before starting treatment with Bortezomib SUN, you should read the package leaflets of all the medicines you have to take in combination with Bortezomib SUN to find information related to these medicines. When using thalidomide, special attention should be paid to pregnancy testing and prevention measures (see Pregnancy and Breast-feeding in this section).

Children and adolescents

Bortezomib SUN should not be used in children and adolescents because it is not known how it will affect them.

Other medicines and Bortezomib SUN

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, tell your doctor if you are using medicines that contain any of the following active substances:

• ketoconazole, to treat fungal infections
• ritonavir, to treat HIV infection
• rifampicin, an antibiotic to treat bacterial infections
• carbamazepine, phenytoin, or phenobarbital used to treat epilepsy
• St. John's Wort (Hypericum perforatum), used for depression or other conditions
• oral antidiabetics.

Pregnancy and breast-feeding

You should not use Bortezomib SUN if you are pregnant unless it is clearly necessary.

Women of childbearing age must use effective contraception during treatment and for up to 8 months after finishing treatment. Talk to your doctor if you want to freeze your eggs before starting treatment.

Men should not father a child while using Bortezomib SUN and must use effective contraception during treatment and for up to 5 months after finishing treatment. Talk to your doctor if you want to preserve your sperm before starting treatment.

You should not breast-feed while using Bortezomib SUN. Ask your doctor when it is safe to restart breast-feeding after finishing your treatment.

Thalidomide causes birth defects and fetal death. When Bortezomib SUN is given in combination with thalidomide, you should follow the thalidomide pregnancy prevention program (see the thalidomide package leaflet).

Driving and using machines

Bortezomib SUN may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or use tools or machines if you experience these side effects; even if you do not experience them, you should still be careful.

3. How to use Bortezomib SUN

Your doctor will tell you the dose of Bortezomib SUN according to your height and weight (body surface area). The usual starting dose of Bortezomib SUN is 1.3 mg/m2 of body surface area twice a week.

Your doctor may change the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain side effects, and your underlying condition (e.g., liver problems).

Progressive multiple myeloma

• When Bortezomib SUN is given alone, you will receive 4 doses of Bortezomib SUN by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day period (3 weeks) is one treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive Bortezomib SUN with the medicines liposomal doxorubicin or dexamethasone.

• When Bortezomib SUN is given with liposomal doxorubicin, you will receive Bortezomib SUN by intravenous or subcutaneous injection in a 21-day treatment cycle. Liposomal doxorubicin 30 mg/m2 is given on day 4 of the 21-day Bortezomib SUN treatment cycle by intravenous infusion after the Bortezomib SUN injection.

You may receive up to 8 cycles (24 weeks).

• When Bortezomib SUN is given with dexamethasone, you will receive Bortezomib SUN by intravenous or subcutaneous injection in a 21-day treatment cycle. Dexamethasone is given orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib SUN treatment cycle.

You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been treated before for multiple myeloma and are nota candidate to receive a blood stem cell transplant, you will receive Bortezomib SUN with the medicines melphalan and prednisone.

In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1 to 4, Bortezomib SUN is given twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, Bortezomib SUN is given once a week on days 1, 8, 22, and 29.

Melphalan (9 mg/m2) and prednisone (60 mg/m2) are given orally during days 1, 2, 3, and 4 of the first week of each cycle.

If you have not received previous treatment for multiple myeloma and area candidate to receive a blood stem cell transplant, you will receive Bortezomib SUN by intravenous or subcutaneous injection with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

• When Bortezomib SUN is given with dexamethasone, you will receive Bortezomib SUN by intravenous or subcutaneous injection in a 21-day treatment cycle. Dexamethasone is given orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib SUN treatment cycle.

You will receive 4 cycles (12 weeks).

• When Bortezomib SUN is given with thalidomide and dexamethasone, the duration of one treatment cycle is 28 days (4 weeks).

Dexamethasone is given orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib SUN treatment cycle. Thalidomide is given orally once a day at a dose of 50 mg up to day 14 of the first cycle, and if tolerated, the thalidomide dose is increased to 100 mg on days 15-28, and from the second cycle onwards, it may be increased further to 200 mg daily.

You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not been treated before for mantle cell lymphoma, you will receive Bortezomib SUN by intravenous or subcutaneous injection with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib SUN is given by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a "rest" period without treatment. The duration of one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines are given by intravenous infusion on day 1 of the 21-day Bortezomib SUN treatment cycle:

Rituximab at a dose of 375 mg/m2, cyclophosphamide at a dose of 750 mg/m2, and doxorubicin at a dose of 50 mg/m2.

Prednisone is given orally at a dose of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the Bortezomib SUN treatment cycle.

How Bortezomib SUN is given

This medicine is given by intravenous or subcutaneous injection. You will be given Bortezomib SUN by a healthcare professional experienced in the use of cytotoxic medicines.

Bortezomib SUN powder must be dissolved before administration. This will be done by a healthcare professional. The reconstituted solution is then injected into a vein or under the skin. The injection into a vein is rapid and takes between 3 and 5 seconds. The injection under the skin is given into the thighs or abdomen.

If you receive more Bortezomib SUN than you should

This medicine will be administered by your doctor or nurse, so it is unlikely that you will receive too much.

In the unlikely event of an overdose, your doctor will monitor you for side effects.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Some of these effects can be serious.

Consult your doctor immediately if you experience any of the following symptoms:

• Muscle cramps, muscle weakness
• Confusion, loss or alteration of vision, blindness, convulsions, headaches
• Difficulty breathing, swelling of the feet or alterations in heart rhythm, high blood pressure, fatigue, fainting
• Cough and difficulty breathing or oppression in the chest.

Treatment with Bortezomib SUN may very frequently cause a decrease in the number of red and white blood cells and platelets in the blood. Therefore, you will need to have regular blood tests before and during treatment with Bortezomib SUN to regularly check the count of blood cells. You may experience a reduction in the number of:

• • Platelets, which can make you more prone to bruising (bruises) or bleeding without apparent injury (e.g., intestinal, stomach, mouth, and gum bleeding or brain or liver bleeding)
• Red blood cells, which can cause anemia, with symptoms such as fatigue and paleness
• White blood cells, which can make you more prone to infections or symptoms similar to those of the flu.

Multiple Myeloma

If you are given Bortezomib SUN for the treatment of multiple myeloma, the adverse effects you may experience are included below:

Very Common Adverse Effects (may affect more than 1 in 10 patients)

• Sensitivity, numbness, tingling, or burning sensation in the skin or pain in the hands or feet due to nerve damage
• Decrease in the number of red and/or white blood cells (see above)
• Fever
• Feeling of discomfort (nausea) or vomiting, loss of appetite
• Constipation with or without swelling (can be severe)
• Diarrhea: if it appears, it is important that you drink more water than usual. Your doctor may give you another medicine to control diarrhea
• Exhaustion (fatigue), feeling of weakness
• Muscle pain, bone pain.

Common Adverse Effects (may affect up to 1 in 10 patients)

• Low blood pressure, sudden drop in blood pressure when standing, which could lead to fainting
• High blood pressure
• Decreased kidney function
• Headache
• Feeling of general discomfort, pain, dizziness, drowsiness, feeling of weakness or loss of consciousness
• Chills
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness
• Herpes zoster (localized, including around the eyes or spread throughout the body)
• Chest pain or difficulty breathing when exercising
• Various types of rashes
• Itching of the skin, skin bumps, or dry skin
• Facial flushing or broken capillaries
• Redness of the skin
• Dehydration
• Heartburn, swelling, belching, flatulence, stomach pain, intestinal or stomach bleeding
• Alteration of liver function
• Sores in the mouth or lip, dry mouth, mouth ulcers, or sore throat
• Weight loss, loss of taste
• Muscle cramps, muscle spasms, muscle weakness, pain in the limbs
• Blurred vision
• Infection of the outer layer of the eye and the inner surface of the eyelids (conjunctivitis)
• Nosebleeds
• Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, restlessness, or agitation, changes in mental state, disorientation
• Swelling of the body, including around the eyes and in other parts of the body.

Uncommon Adverse Effects (may affect up to 1 in 100 patients)

• Heart problems, including heart attack, angina pectoris
• • Severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome)
• Hot flashes
• Discoloration of the veins
• Inflammation of the spinal nerves
• Ear problems, ear bleeding
• Underactive thyroid gland
• Budd-Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins)
• Changes or anomalies in intestinal function
• Cerebral hemorrhage
• Yellowing of the eyes and skin (jaundice)
• Severe allergic reaction (anaphylactic shock), whose signs can be difficulty breathing, pain or oppression in the chest and/or feeling of dizziness/fainting, intense itching of the skin or skin bumps, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse
• Breast disorders
• Vaginal tearing
• Genital inflammation
• Inability to tolerate alcohol consumption
• Emaciation or loss of body mass
• Increased appetite
• Fistula
• Joint effusion
• Cysts in the joint lining (synovial cysts)
• Fracture
• Breakdown of muscle fibers that can cause other complications
• Liver swelling, liver bleeding
• Kidney cancer
• Skin disease similar to psoriasis
• Skin cancer
• Pallor of the skin
• Increased platelets or plasma cells (a type of white blood cell) in the blood
• Blood clot in small blood vessels (thrombotic microangiopathy)
• Abnormal reaction to blood transfusions
• Partial or total loss of vision
• Loss of libido
• Drooling
• Bulging eyes
• Sensitivity to light
• Rapid breathing
• Rectal pain
• Gallstones
• Hernia
• Wounds
• Weak or brittle nails
• Abnormal protein deposits in vital organs
• Coma
• Intestinal ulcers
• Multi-organ failure
• Death.

Mantle Cell Lymphoma

If you are given Bortezomib SUN along with other medicines for the treatment of mantle cell lymphoma, the adverse effects you may experience are included below:

Very Common Adverse Effects (may affect more than 1 in 10 patients)

• Pneumonia
• Loss of appetite
• Sensitivity, numbness, tingling, or burning sensation in the skin or pain in the hands or feet due to nerve damage
• Nausea or vomiting
• Diarrhea
• Sores in the mouth
• Constipation
• Muscle pain, bone pain
• Hair loss and abnormal hair texture
• Exhaustion, feeling of weakness
• Fever.

Common Adverse Effects (may affect up to 1 in 10 patients)

• Herpes zoster (localized, including around the eyes or spread throughout the body)
• Herpes virus infection
• Bacterial and viral infections
• Respiratory infections, bronchitis, cough with phlegm, flu-like illness
• Fungal infections
• Hypersensitivity (allergic reaction)
• Inability to produce sufficient insulin or resistance to normal insulin levels
• Fluid retention
• Difficulty or problems sleeping
• Loss of consciousness
• Alteration of consciousness level, confusion
• Dizziness
• Increased heart rate, high blood pressure, sweating
• Abnormal vision, blurred vision
• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
• High or low blood pressure
• Sudden drop in blood pressure when standing, which could lead to fainting
• Difficulty breathing with exercise
• Cough
• Wheezing
• Ear ringing or ear discomfort
• Intestinal or stomach bleeding
• Heartburn
• Stomach pain, swelling
• Difficulty swallowing
• Infection or inflammation of the stomach and intestine
• Stomach pain
• Sores in the mouth or lip, sore throat
• Alteration of liver function
• Itching of the skin
• Redness of the skin
• Rash
• Muscle spasms
• Urinary tract infections
• Pain in the limbs
• Swelling of the body, including around the eyes and in other parts of the body
• Chills
• Redness and pain at the injection site
• Feeling of general discomfort
• Weight loss
• Weight gain.

Uncommon Adverse Effects (may affect up to 1 in 100 patients)

• Hepatitis
• Severe allergic reaction (anaphylactic reaction), whose signs can be difficulty breathing, pain or oppression in the chest and/or feeling of dizziness/fainting, intense itching of the skin or skin bumps, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse
• Movement disorders, paralysis, tremors
• Dizziness
• Hearing loss, deafness
• Disorders that affect the lungs, preventing the body from receiving a sufficient amount of oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that can become shallow, difficult, or stop, rapid breathing
• Blood clots in the lungs
• Yellowing of the eyes and skin (jaundice)
• Cyst in the eyelid (chalazion), red and swollen eyelids.

Rare Adverse Effects (may affect up to 1 in 1,000 patients)

• Blood clot in small blood vessels (thrombotic microangiopathy).
• Severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is 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 contribute to providing more information on the safety of this medicine.

5. Storage of Bortezomib SUN

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the vial and on the packaging after CAD.

Do not store above 25 °C. Keep the vial in the outer packaging to protect it from light.

From a microbiological point of view, the reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user. However, the reconstituted solution is stable for 8 hours at 25 °C stored in the original vial and/or a syringe; the total storage time of the reconstituted medicine should not exceed 8 hours before administration.

Bortezomib SUN is exclusively for single use. The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

6. Container Contents and Additional Information

Composition of Bortezomib SUN

• The active ingredient is bortezomib. Each vial contains 3.5 mg of bortezomib (as boronic acid mannitol ester).
• The other component is mannitol (E421).

Reconstitution for intravenous administration:

After reconstitution, 1 ml of the solution for intravenous injection contains 1 mg of bortezomib.

Reconstitution for subcutaneous administration:

After reconstitution, 1 ml of the solution for subcutaneous injection contains 2.5 mg of bortezomib.

Appearance of Bortezomib SUN and Container Contents

Bortezomib SUN 3.5 mg powder for solution for injection EFG is a lyophilized tablet or a lyophilized powder, white or off-white.

Each container of Bortezomib SUN contains a 10 ml glass vial with a light green aluminum cap, in a transparent blister.

Marketing Authorization Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Denmark/Estonia/Greece/Croatia/Ireland/Iceland/Cyprus/

Latvia/Lithuania/Luxembourg/Luxemburg/Hungary/

Malta/Netherlands/Norway/Austria/Portugal/

Slovenia/Slovak Republic/Finland/Sweden

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands/Pays-Bas/Niederlande/Нидерланды/Nizozemsko/Nederlandene/Holland/Ολλανδία/Nizozemska/

Niderlande/Nyderlandai/Pays-Bas/Niederlande/Hollandia/L-Olanda/Nederland/Nederland/Niederlande/Países Baixos/

Nizozemska/Holandsko/Alankomaat/Nederländerna/Nederländerna

Tel./Тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./

+31 (0)23 568 5501

Germany

Sun Pharmaceuticals Germany GmbH

Hemmelrather Weg 201

51377 Leverkusen

Germany

tel. +49 (0) 214 403 99 0

Spain

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

tel. +34 93 342 78 90

France

Sun Pharma France

11-15, Quai de Dion Bouton

92800 Puteaux

France

tel. +33 1 41 44 44 50

Italy

Sun Pharma Italia Srl

Viale Giulio Richard, 1

20143 Milano

Italy

tel. +39 02 33 49 07 93

Poland

Ranbaxy (Poland) Sp. z o. o.

ul. Kubickiego 11

02-954 Warszawa

Poland

Tel. +48 22 642 07 75

Romania

Terapia S.A.

Str. Fabricii nr 124

Cluj-Napoca, Judetul Cluj

Romania

Tel. +40 (264) 501 500

Date of Last Revision of this Leaflet:

Other Sources of Information

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

This information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib SUN is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

SINCE BORTEZOMIB SUN IS FREE OF PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1. Preparation of a 3.5 mg vial: carefully add 3.5 mlof sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib SUN powder using a suitable-sized syringe without removing the vial cap. The dissolution of the lyophilized powder is completed in less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. The solution should be colorless and transparent, with a final pH of 4 to 7. It is not necessary to check the pH of the solution.

1. Before administration, visually inspect the solution to rule out the presence of particles and discoloration. If any discoloration or particles are observed, the solution should be discarded. Check that the correct dose is being used for intravenous administration (1 mg/ml).

1. The reconstituted solution lacks preservatives and should be used immediately after preparation. However, the chemical and physical stability during use has been demonstrated for 8 hours at 25 °C in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 8 hours before administration. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user.

It is not necessary to protect the reconstituted product from light.

1. ADMINISTRATION METHOD

• Once dissolved, withdraw the appropriate amount of the reconstituted solution based on the calculated dose based on the patient's Body Surface Area.
• Confirm the dose and concentration contained in the syringe before use (check that the syringe is marked for intravenous administration).
• Inject the solution through a peripheral or central intravenous catheter in a vein as a bolus over 3-5 seconds.
• Flush the peripheral or intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

BORTEZOMIB SUN 3.5 MG POWDER FOR SOLUTION FOR INJECTION EFG SHOULD BE ADMINISTERED ONLY BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

1. DISPOSAL

A vial is for single use and the remaining solution should be discarded.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

This information is intended for healthcare professionals only:

Only the 3.5 mg vial can be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib SUN is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

SINCE BORTEZOMIB SUN IS FREE OF PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1. Preparation of a 3.5 mg vial: carefully add 1.4 mlof sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib SUN powder using a suitable-sized syringe without removing the vial cap. The dissolution of the lyophilized powder is completed in less than 2 minutes.

The concentration of the resulting solution will be 2.5 mg/ml. The solution should be colorless and transparent, with a final pH of 4 to 7. It is not necessary to check the pH of the solution.

1. Before administration, visually inspect the solution to rule out the presence of particles and discoloration. If any discoloration or particles are observed, the solution should be discarded. Check that the correct dose is being used for subcutaneous administration (2.5 mg/ml).

1. The reconstituted solution lacks preservatives and should be used immediately after preparation. However, the chemical and physical stability during use has been demonstrated for 8 hours at 25 °C in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 8 hours before administration. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user.

It is not necessary to protect the reconstituted product from light.

1. ADMINISTRATION METHOD

• Once dissolved, withdraw the appropriate amount of the reconstituted solution based on the calculated dose based on the patient's Body Surface Area.
• Confirm the dose and concentration contained in the syringe before use (check that the syringe is marked for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45-90°.
• The reconstituted solution is administered subcutaneously into the thigh (right or left) or abdomen (right or left side).
• The injection sites should be rotated with each injection.
• If local reactions occur at the injection site after subcutaneous injection of Bortezomib SUN, either a less concentrated solution of Bortezomib SUN (1 mg/ml instead of 2.5 mg/ml) can be administered subcutaneously or it is recommended to switch to intravenous injection.

BORTEZOMIB SUN 3.5 MG POWDER FOR SOLUTION FOR INJECTION EFG SHOULD BE ADMINISTERED ONLY BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

1. DISPOSAL

A vial is for single use and the remaining solution should be discarded.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.