BORTEZOMIB DR REDDYS 2.5 mg/mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bortezomib Dr. Reddys 2.5 mg 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.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Bortezomib Dr. Reddys and what is it used for

Bortezomib Dr. Reddys 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 Dr. Reddys is used to treat multiple myeloma (a cancer of the bone marrow) 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 whose disease has not been previously treated and who are not suitable for high-dose chemotherapy before a blood stem cell transplant.
• in combination with the medicines dexamethasone or dexamethasone and thalidomide, in patients whose disease has not been previously treated and who receive high-dose chemotherapy before a blood stem cell transplant (induction treatment).

Bortezomib Dr. Reddys is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients 18 years of age or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients whose disease has not been previously treated 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 Dr. Reddys

Do not use Bortezomib Dr. Reddys

• 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 blood cell counts
• bleeding problems and/or low platelet count in the blood
• diarrhea, constipation, nausea, or vomiting
• 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, 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 Dr. Reddys to check your blood cell count regularly.

You must inform your doctor if you have mantle cell lymphoma and are being given rituximab with Bortezomib Dr. Reddys:

• if you think you currently have or have had hepatitis infection in the past. In a few cases, patients who have had hepatitis B may 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 Dr. Reddys, you should read the package leaflets of all the medicines you need to take with Bortezomib Dr. Reddys for information about 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 Dr. Reddys should not be used in children and adolescents because it is not known how it will affect them.

Other medicines and Bortezomib Dr. Reddys

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 Dr. Reddys if you are pregnant unless it is clearly necessary.

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

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

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

Driving and using machines

Bortezomib Dr. Reddys 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.

3. How to use Bortezomib Dr. Reddys

Your doctor will tell you the dose of Bortezomib Dr. Reddys according to your height and weight (body surface area). The usual starting dose of Bortezomib Dr. Reddys 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 Dr. Reddys is given alone, you will receive 4 doses of Bortezomib Dr. Reddys 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 Dr. Reddys with the medicines liposomal doxorubicin or dexamethasone.

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

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

When Bortezomib Dr. Reddys is given with dexamethasone, you will receive Bortezomib Dr. Reddys by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone 20 mg will be given by mouth on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib Dr. Reddys treatment cycle.

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

Previously untreated multiple myeloma

If you have not been previously treated for multiple myeloma and are nota candidate for a blood stem cell transplant, you will receive Bortezomib Dr. Reddys with two other 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 Dr. Reddys will be given twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, Bortezomib Dr. Reddys will be given once a week on days 1, 8, 22, and 29. Melphalan (9 mg/m2) and prednisone (60 mg/m2) will be given by mouth during days 1, 2, 3, and 4 of the first week of each cycle.

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

When Bortezomib Dr. Reddys is given with dexamethasone, you will receive Bortezomib Dr. Reddys by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone will be given by mouth in doses of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Dr. Reddys treatment cycle.

You will receive 4 cycles (12 weeks).

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

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

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

Previously untreated mantle cell lymphoma

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

Bortezomib Dr. Reddys will be 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 will be given by intravenous infusion on day 1 of the 21-day Bortezomib Dr. Reddys 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 will be given by mouth at a dose of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the Bortezomib Dr. Reddys treatment cycle.

How Bortezomib Dr. Reddys is given

Bortezomib Dr. Reddys must be administered by a healthcare professional experienced in the use of cytotoxic medicines.

This medicine is for subcutaneous use (injection under the skin), and after dilution, also for intravenous use (injection into a vein). The injection into a vein is rapid and lasts between 3 and 5 seconds. The injection under the skin is given into the thighs or abdomen.

If you receive more Bortezomib Dr. Reddys 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.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone: 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these effects may be serious.

If you are given Bortezomib Dr. Reddys for multiple myeloma or mantle cell lymphoma, tell your doctor immediately if you notice any of the following symptoms:

• muscle cramps, muscle weakness
• confusion, vision loss or changes, blindness, seizures, headaches
• difficulty breathing, swelling of the feet or changes in heart rhythm, high blood pressure, fatigue, fainting
• coughing and difficulty breathing or chest tightness.

Treatment with Bortezomib Dr. Reddys may very commonly 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 Dr. Reddys to check your blood cell count regularly. 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, or gum bleeding, or bleeding in the brain or liver)
• 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 flu-like symptoms.

If you are given Bortezomib Dr. Reddys for the treatment of multiple myeloma, the side effects you may experience are listed below:

Very common side 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
• Reduction in the number of red and/or white blood cells (see above)
• Fever
• Feeling sick (nausea) or vomiting, loss of appetite
• Constipation with or without swelling (can be severe)
• Diarrhea: if it occurs, it is important to drink more water than usual. Your doctor may give you another medicine to control diarrhea
• Fatigue (tiredness), feeling weak
• Muscle pain, bone pain

Common side effects (may affect up to 1 in 10 patients)

• Low blood pressure, sudden drop in blood pressure when standing up, which could lead to fainting
• High blood pressure
• Decreased kidney function
• Headache
• General feeling of being unwell, pain, dizziness, lightheadedness, feeling weak or loss of consciousness
• Chills
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness
• Shingles (localized, including around the eyes, or widespread)
• Chest pain or difficulty breathing when exercising
• Different types of rashes
• Itching, skin lumps, or dry skin
• Flushing of the face or broken small blood vessels
• Redness of the skin
• Dehydration
• Heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding
• Abnormal liver function
• Mouth sores 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 sleeping, sweating, anxiety, mood changes, depression, restlessness, or agitation, changes in mental state, disorientation
• Swelling of the body, including around the eyes and in other parts of the body

Adverse effects infrequently encountered (may affect up to 1 in 100 patients)

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
• Kidney failure
• Inflammation of a vein, blood clots in the veins and lungs
• Blood coagulation problems
• Insufficient circulation
• Inflammation of the heart lining or fluid around the heart
• Infections, including urinary tract infections, flu, herpes virus infection, ear infection, and cellulitis
• Bloody stools or bleeding in the mucous membranes, for example, in the mouth or vagina
• Cerebrovascular disorders
• Paralysis, seizures, falls, movement disorders, alterations or changes in, or decreased sensitivity (touch, hearing, taste, smell), attention disorders, tremors, jerks
• Arthritis, including inflammation of the joints of the hands and feet and jaw
• Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that can become shallow, difficult, or stop, panting
• Hiccup, speech disorders
• Increased or decreased urine production (due to kidney damage), pain when urinating or blood/proteins in the urine, fluid retention
• Altered level of consciousness, confusion, altered or lost memory
• Hypersensitivity
• Hearing loss, deafness or ringing in the ears, ear discomfort
• Hormonal changes that can affect salt and water absorption
• Overactivity of the thyroid gland
• Inability to produce sufficient insulin or resistance to normal insulin levels
• Eye irritation or inflammation, overly watery eyes, eye pain, dry eyes, eye infections, eyelid cyst (chalazion), reddened and swollen eyelids, tearful eyes (lacrimation), abnormal vision, eye bleeding
• Lymph node swelling
• Joint or muscle stiffness, feeling of heaviness, groin pain
• Hair loss and abnormal hair texture
• Allergic reactions
• Redness or pain at the injection site
• Mouth pain
• Mouth or esophageal infections, ulcers in the mouth, esophagus, stomach, and intestine, sometimes associated with pain or bleeding, scant intestinal movement (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood
• Skin infections
• Bacterial and viral infections
• Dental infections
• Pancreatitis, bile duct obstruction
• Genital pain, difficulty achieving an erection
• Weight gain
• Thirst
• Hepatitis
• Disorders at the injection site or related to the injection device
• Skin reactions and disorders (which can be severe and life-threatening), skin ulcers
• Bruises, falls, and injuries
• Inflammation or bleeding of blood vessels that can appear as small red or purple spots (usually on the legs) to large bruise-like patches under the skin or tissue
• Benign cysts
• A severe and reversible brain disorder that includes seizures, high blood pressure, headaches, fatigue, confusion, blindness, or other vision problems

Rare adverse effects (may affect up to 1 in 1,000 patients)

• Heart problems, including heart attack, angina pectoris
• Severe nerve inflammation, which can cause paralysis and breathing difficulties (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 pressure in the chest and/or feeling of dizziness/fainting, intense itching of the skin or lumps 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 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
• Pale 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 duct 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 Dr. Reddys along with other medications for the treatment of mantle cell lymphoma, the adverse effects you may experience include the following:

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
• Altered level of consciousness, 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
• Hiccup
• Ringing in the ears, ear discomfort
• Intestinal or stomach bleeding
• Heartburn
• Stomach pain, bloating
• Difficulty swallowing
• Stomach and intestine infection or inflammation
• Stomach pain
• Mouth or lip sores, sore throat
• Abnormal liver function
• Itching skin
• Redness of the skin
• Rash
• Muscle spasms
• Urinary tract infection
• Pain in the limbs
• Body swelling, 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 pressure in the chest and/or feeling of dizziness/fainting, intense itching of the skin or lumps on the skin, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse
• Movement disorders, paralysis, jerks
• Dizziness
• Hearing loss, deafness
• Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that can become shallow, difficult, or stop, panting
• Blood clots in the lungs
• Yellowing of the eyes and skin (jaundice)
• Eyelid cyst (chalazion), reddened 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 breathing difficulties (Guillain-Barré syndrome)

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that is not listed in this leaflet. 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 medication.

5. Storage of Bortezomib Dr. Reddys

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the vial and on the packaging after EXP. Store in a refrigerator (between 2°C and 8°C). Keep the vial in the outer packaging to protect it from light.

After first opening

Chemical and physical stability in use of the undiluted solution has been demonstrated for 72 hours at 25°C in both the vial and the PP syringe with normal indoor lighting, for 12 days at 25°C and for 40 days at 2-8°C in the PP syringe if protected from light.

After dilution

Chemical and physical stability in use of the diluted solution (1.0 mg/ml bortezomib diluted with 9 mg/ml (0.9%) sodium chloride) has been demonstrated for 72 hours at 25°C in both the vial and the PP syringe with normal indoor lighting, for 12 days at 25°C and for 40 days at 2-8°C in the vial or PP syringe if protected from light.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C.

Bortezomib Dr. Reddys is for single use only. Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

6. Package contents and additional information

Composition of Bortezomib Dr. Reddys

• The active ingredient is bortezomib. Each 1 ml or 1.4 ml vial of injectable solution contains 2.5 mg/ml of bortezomib (as boronic acid ester of mannitol).
• The other ingredients are mannitol (E421), sodium chloride, and water for injections.

Intravenous route:

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

Subcutaneous route:

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

Appearance of the product and package contents

Bortezomib Dr. Reddys powder for injectable solution is a clear, colorless solution.

Transparent glass vial Type I with rubber stopper and gray aluminum cap containing 1 ml of injectable solution.

Transparent glass vial Type I with rubber stopper and yellow aluminum cap containing 1.4 ml of injectable solution.

Package sizes

1 vial of 1 ml

1 vial of 1.4 ml

Not all package sizes may be marketed.

Marketing authorization holder

Reddy Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona (Spain)

Manufacturer

betapharm Arzneimittel GmbH,

Kobelweg 95,

86156 Augsburg

Germany

or

Pharmadox Healthcare Ltd.,

KW20A Kordin Industrial Park

Paola PLA 3000

Malta

or

Rual Laboratories SRL

313, Splaiul Unirii, Building H

1st floor, sector 3

030138 Bucuresti

Romania

This medication is authorized in the member states of the European Economic Area with the following names:

Date of last revision of this leaflet:May 2024

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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The following information is intended only for healthcare professionals:

Note: Bortezomib Dr. Reddys 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 who are part of the staff should not handle this medication.

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

Bortezomib Dr. Reddys 2.5 ml solution for injection IS FOR SUBCUTANEOUS OR INTRAVENOUS ADMINISTRATION ONLY. It should not be administered by other routes. Administration by the intrathecal route has resulted in death.

1.

1. Preparation of a 2.5 mg/1 ml vial: add 1.6 mlof 9 mg/ml (0.9%) sodium chloride injectable solution to the vial containing Bortezomib.

Preparation of a 3.5 mg/1.4 ml vial: add 2.2 mlof 9 mg/ml (0.9%) sodium chloride injectable solution to the vial containing Bortezomib.

Each vial contains an additional 0.1 ml excess. Consequently, each 1 ml and 1.4 ml vial contains 2.75 mg and 3.75 mg of bortezomib, respectively.

The resulting solution concentration will be 1 mg/ml. The solution should be clear and transparent.

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).

The diluted solution does not contain preservatives and should be used immediately after preparation. However, it has been demonstrated that the chemical and physical stability for use is 24 hours at 20°C - 25°C. The total storage time of the diluted medication should not exceed 24 hours prior to administration. If the diluted solution is not used immediately, the storage times and conditions before use are the responsibility of the user. It is not necessary to protect the diluted medication from light.

2.

1. After dilution, withdraw the appropriate amount of diluted solution according to the calculated dose based on the patient's body surface area.
2. Confirm the dose and concentration contained in the syringe before use (verify that the syringe is marked for intravenous use).
3. Inject the solution through a peripheral or central intravenous catheter in a vein, using a bolus injection of 3 to 5 seconds.
4. Flush the peripheral or intravenous catheter with 9 mg/ml (0.9%) sodium chloride solution.

3.

1. Bortezomib solution for injection is ready for use by the subcutaneous route.

The solution concentration is 2.5 mg/ml. The solution is clear and transparent.

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).
2. The product does not contain preservatives and should be used immediately after withdrawing the appropriate amount of solution from the vial.

1. During preparation for administration or during administration itself, it is not necessary to protect the medication from light.

4.

1. Extract the appropriate amount of diluted solution based on the calculated dose according to the patient's body surface area.
2. Confirm the dose and concentration contained in the syringe before use (verify that the syringe is marked for subcutaneous use).
3. Inject the solution subcutaneously at an angle of 45°-90°.
4. The solution is administered subcutaneously in the thighs (right or left) or in the abdomen (to the right or left).
5. The injection sites should be rotated for subsequent injections.
6. In the event of a reaction at the injection site after subcutaneous administration of injectable bortezomib, a solution of bortezomib with a lower concentration (1 mg/ml instead of 2.5 mg/ml) may be administered subcutaneously, or alternatively, it is recommended to switch to intravenous injection.

5.

A vial is for single use and any remaining solution must be discarded.

The disposal of unused medication or all residual material must be carried out in accordance with local regulations.