BORTEZOMIB EVER PHARMA 2.5 mg/mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bortezomib EVER Pharma 2.5 mg/ml solution for injection

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.

• Keep this leaflet, as 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 is Bortezomib EVER Pharma and what is it used for
2. What you need to know before you use Bortezomib EVER Pharma
3. How to use Bortezomib EVER Pharma
4. Possible side effects
5. Storage of Bortezomib EVER Pharma
6. Contents of the pack and other information

1. What is Bortezomib EVER Pharma and what is it used for

This medicine contains the active substance bortezomib, a “proteasome inhibitor”. Proteasomes play an important role in controlling cell function and growth. Bortezomib can destroy cancer cells by interfering with their function.

Bortezomib is used to treat multiple myeloma (a type of bone marrow cancer) in patients aged 18 and over:

• alone or with the medicines doxorubicin liposomal pegylated or dexamethasone, for patients whose disease is getting worse (in progression) after receiving at least one previous treatment and for those patients whose stem cell transplant did not work or is not suitable.
• in combination with the medicines melphalan and prednisone, for patients whose disease has not been treated before and who are not suitable for high-dose chemotherapy before a stem cell transplant.
• in combination with the medicines dexamethasone or dexamethasone plus thalidomide, in patients whose disease has not been treated before and who receive high-dose chemotherapy before a stem cell transplant (induction treatment).

Bortezomib is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients aged 18 and over in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients whose disease has not been treated before and for those patients who are not considered suitable for a stem cell transplant.

2. What you need to know before you use Bortezomib EVER Pharma

Do not use Bortezomib EVER Pharma

• 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 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 your 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 changes, and difficulty breathing.
• memory loss, changes in thinking, 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 to check your blood cell count regularly.

You must tell your doctor if you have mantle cell lymphoma and are given rituximab with bortezomib:

• if you think you have or have had hepatitis infection in the past. In a few cases, patients who have had hepatitis B can have repeated attacks of hepatitis, which can be fatal. If you have a history of hepatitis B infection, you will be closely monitored by your doctor for signs of active hepatitis B.

Before starting treatment with bortezomib, you should read the package leaflets of all the medicines you need to take with bortezomib to find out about the information related to these medicines.

When using thalidomide, special attention should be paid to pregnancy testing and prevention measures (see Pregnancy and Breastfeeding in this section).

Children and adolescents

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

Using Bortezomib EVER Pharma with other medicines

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 breastfeeding

Do not use bortezomib if you are pregnant unless clearly necessary.

Both men and women using bortezomib must use effective contraception during and for up to 3 months after treatment. If, despite these measures, you become pregnant, inform your doctor immediately.

Do not breastfeed while using bortezomib. Ask your doctor when it is safe to restart breastfeeding after finishing your treatment.

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

Driving and using machines

Bortezomib 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 cautious.

Bortezomib EVER Pharma contains sodium

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

3. How to use Bortezomib EVER Pharma

Your doctor will tell you the dose of bortezomib based on your height and weight (body surface area). The usual starting dose of bortezomib 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 is given alone, you will receive 4 doses of bortezomib 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 with the medicines doxorubicin liposomal pegylated or dexamethasone.

When bortezomib is given with doxorubicin liposomal pegylated, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and doxorubicin liposomal pegylated 30 mg/m2 will be given by intravenous infusion on day 4 of the bortezomib 21-day treatment cycle, after the bortezomib injection. You may receive up to 8 cycles (24 weeks).

When bortezomib is given with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone 20 mg will be given orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of the bortezomib 21-day treatment cycle. You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been treated for multiple myeloma before and are nota candidate for a stem cell transplant, you will receive bortezomib with two other medicines; melphalan and prednisone.In this case, one treatment cycle lasts 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1 to 4, bortezomib is given twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, bortezomib 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 the first 4 days of each cycle.

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

When bortezomib is given with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone will be given orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the bortezomib 21-day treatment cycle. You will receive 4 cycles (12 weeks).

When bortezomib is given with thalidomide and dexamethasone, one treatment cycle lasts 28 days (4 weeks).

Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the bortezomib 28-day treatment cycle, and thalidomide is given orally once daily 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 for mantle cell lymphoma before, you will receive bortezomib by intravenous or subcutaneous injection with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib is given by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a “rest” period without treatment. One treatment cycle lasts 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 bortezomib 21-day 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 treatment cycle.

How Bortezomib EVER Pharma is given

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

The solution is injected into a vein or under the skin. The injection into a vein is rapid, lasting between 3 and 5 seconds. The injection under the skin is given into the thighs or abdomen.

If you receive more Bortezomib EVER Pharma than you should

This medicine will be given to you 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.

If you are administered bortezomib for multiple myeloma or mantle cell lymphoma, report immediately to your doctor if you observe 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 alteration of heart rhythm, high blood pressure, fatigue, fainting
• Cough and difficulty breathing or oppression in the chest.

Treatment with bortezomib can very frequently cause a decrease in the number of red and white blood cells and platelets in the blood. Therefore, you will need to undergo regular blood tests before and during treatment with bortezomib, to regularly check your blood cell count. 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.

If you are administered bortezomib 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 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 rupture of small blood vessels
• 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)
• Flushing
• 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 bumps on the skin, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse
• Breast disorders
• Vaginal tear
• Genital inflammation
• Inability to tolerate alcohol consumption
• Emaciation or loss of body mass
• Increased appetite
• Fistula
• Joint effusion
• Cysts in the lining of the joints (synovial cysts)
• Fracture
• Breakdown of muscle fibers that causes 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
• Bile stones
• Hernia
• Wounds
• Weak or brittle nails
• Abnormal protein deposits in vital organs
• Coma
• Intestinal ulcers
• Multi-organ failure
• Death

If you are administered bortezomib together 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 hands or feet due to nerve damage
• Nausea or vomiting
• Diarrhea
• Mouth ulcers
• 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
• Feeling of 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 when exercising
• Cough
• Hiccup
• Ringing in the ears, 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 bumps on the skin, 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 are 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 prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Bortezomib EVER Pharma

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. The expiration date is the last day of the month indicated.

Store in the refrigerator (2 °C – 8 °C).

Keep the vial in the outer packaging to protect it from light.

The solution must be used immediately after the first opening/dilution. If the solution (diluted) is not used immediately, the storage times and conditions before use are the responsibility of the user. However, when the solution is stored in the original vial and/or in a polypropylene syringe, the solution (diluted) is stable for 28 days at 2 °C - 8 °C and up to 25 °C protected from light, and for 24 hours up to 25 °C in normal indoor lighting conditions.

Regarding the stability in the syringe, the same storage time applies to the diluted solution and the undiluted solution.

Bortezomib 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 EVER Pharma

The active ingredient is bortezomib. 1 milliliter of injectable solution contains 2.5 milligrams of bortezomib (as boric acid mannitol ester). Each vial with 1 milliliter of injectable solution contains 2.5 milligrams of bortezomib (as boric acid mannitol ester). Each vial with 1.4 milliliters of injectable solution contains 3.5 milligrams of bortezomib (as boric acid mannitol ester).

Each vial contains an additional overfill of 0.2 ml.

The other components are mannitol (E421), sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injectable preparations.

Vial of 1 ml

Subcutaneous route: The product is ready to use with its concentration of 2.5 mg/ml.

Intravenous route: Add 1.8 ml of 0.9% sodium chloride injection solution to obtain a final concentration of 1 mg/ml.

Vial of 1.4 ml

Subcutaneous route: The product is ready to use with its concentration of 2.5 mg/ml.

Intravenous route: Add 2.4 ml of 0.9% sodium chloride injection solution to obtain a final concentration of 1 mg/ml.

Appearance of Bortezomib EVER Pharma and Container Contents

Bortezomib EVER Pharma 2.5 mg/ml injectable solution is a clear, colorless to pale yellow solution.

Bortezomib EVER Pharma is presented in a colorless glass vial with a rubber stopper and an aluminum cap with a plastic flip-off closure.

Package Sizes

1 vial of 1 ml (2.5 mg/1 ml)

5 vials of 1 ml (2.5 mg/1 ml)

1 vial of 1.4 ml (3.5 mg/1.4 ml)

5 vials of 1.4 ml (3.5 mg/1.4 ml)

Only some package sizes may be marketed.

Marketing Authorization Holder

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Manufacturer

EVER Pharma Jena GmbH

Otto Schott Str. 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

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

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicinal product is authorized in the EEA Member States under the following names:

Date of Last Revision of this Leaflet: 09/2021

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es)

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This information is intended for healthcare professionals only:

1. PREPARATION FOR INTRAVENOUS INJECTION

Note: Bortezomib 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. Pregnant women should not handle this medicinal product.

AS BORTEZOMIB DOES NOT CONTAIN PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1. Preparation of a 1 ml vial: add 1.8 millilitersof sterile 0.9% sodium chloride injection solution to the vial containing bortezomib.

Or

Preparation of a 1.4 ml vial: add 2.4 millilitersof sterile 0.9% sodium chloride injection solution to the vial containing bortezomib.

The concentration of the resulting solution will be 1 mg/ml. The solution should be clear, colorless to pale yellow, 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 administration by intravenous route(1 mg/ml).

1.3 The solution does not contain preservatives and should be used immediately after preparation. However, the chemical and physical stability of the diluted solution has been demonstrated for:

• 28 days at 2 °C - 8 °C and protected from light
• 28 days at 25 °C and protected from light
• 24 hours, when stored at 25 °C and under normal indoor lighting conditions in the original vial and/or in a polypropylene syringe.

If the diluted solution is not used immediately, the storage times and conditions prior to use are the responsibility of the user.

1. ADMINISTRATION

• Once diluted, withdraw the appropriate amount of the diluted solution based on the calculated dose according to 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, using a bolus injection of 3-5 seconds.
• Flush the peripheral or intravenous catheter with sterile 0.9% sodium chloride solution.

Bortezomib EVER Pharma 2.5 mg/ml injectable solution SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

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

The disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations for cytotoxic agents.

This information is intended for healthcare professionals only:

1. PREPARATION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib 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. Pregnant women should not handle this medicinal product.

AS BORTEZOMIB DOES NOT CONTAIN PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1.1 Bortezomib is ready to use. The concentration of the solution will be 2.5 mg/ml. The solution is clear, colorless to pale yellow, with a pH of 4.0 to 5.5. It is not necessary to check the pH of the solution.

1.2 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 administration by subcutaneous route(2.5 mg/ml).

1.3 The solution does not contain preservatives and should be used immediately after withdrawing the appropriate amount of solution. However, the chemical and physical stability of the solution has been demonstrated for:

o 28 days at 2 °C - 8 °C and protected from light

o 28 days at 25 °C and protected from light

o 24 hours, when stored at 25 °C and under normal indoor lighting conditions in the original vial and/or in a polypropylene syringe.

If the solution is not used immediately, the storage times and conditions prior to use are the responsibility of the user.

During preparation for administration and during administration itself, it is not necessary to protect the medicinal product from light.

1. ADMINISTRATION

• Withdraw the appropriate amount of solution based on the calculated dose according to 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 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, either a less concentrated solution (1 mg/ml instead of 2.5 mg/ml) can be administered subcutaneously or intravenous injection is recommended.

Bortezomib EVER Pharma 2.5 mg/ml injectable solution SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

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

The disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations for cytotoxic agents.