Bortezomib Tzf

Package Leaflet: Information for the User

Bortezomib TZF, 3.5 mg, Powder for Solution for Injection

bortezomib

Read All of This Leaflet Carefully Before You Start Using This Medicine.

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

Table of Contents of the Leaflet

• 1. What is Bortezomib and What is it Used For
• 2. Important Information Before You Use Bortezomib
• 3. How to Use Bortezomib
• 4. Possible Side Effects
• 5. How to Store Bortezomib
• 6. Contents of the Pack and Other Information

1. What is Bortezomib and What is it Used For

Bortezomib contains the active substance bortezomib, which is a so-called "proteasome inhibitor". Proteasomes play a crucial role in controlling cell function and cell division. By disrupting their function, bortezomib can cause the death of cancer cells.

Bortezomib is used to treat multiple myeloma (a type of bone marrow cancer) in adults over 18 years of age:

• as a single medicine or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone in patients whose disease has progressed after at least one prior treatment and for whom hematopoietic stem cell transplantation was not successful or not possible;
• in combination with melphalan and prednisone in patients who have not been treated before and do not qualify for high-dose chemotherapy with hematopoietic stem cell transplantation;
• in combination with dexamethasone or dexamethasone plus thalidomide in patients who have not been treated before, before high-dose chemotherapy with hematopoietic stem cell transplantation (induction treatment).

Bortezomib is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in adults over 18 years of age in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone in patients who have not been treated before and do not qualify for hematopoietic stem cell transplantation.

2. Important Information Before You Use Bortezomib

When Not to Use Bortezomib

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

Warnings and Precautions

Before starting treatment with Bortezomib, you should discuss with your doctor if:

• you have a low number of red or white blood cells;
• you have bleeding disorders and (or) a low platelet count;
• you have diarrhea, constipation, nausea, or vomiting;
• you have had fainting, dizziness, or lightheadedness in the past;
• you have kidney disease;
• you have moderate to severe liver function disorders;
• you have had numbness, tingling, or pain in your hands and feet (symptoms of neuropathy);
• you have heart disease or blood pressure problems;
• you have shortness of breath or a cough;
• you have seizures;
• you have shingles (localized around the eyes or widespread on the body);
• you have symptoms of tumor lysis syndrome, such as painful muscle spasms, muscle weakness, confusion, vision loss, or shortness of breath;
• you have memory disorders, thinking disorders, difficulty walking, or vision loss. These may be symptoms of a serious brain infection, and your doctor may recommend further tests and monitoring.

Before starting treatment with Bortezomib and during treatment, you will have regular blood tests to check your blood cell count.

If you are taking Bortezomib for mantle cell lymphoma and are also taking rituximab, you should tell your doctor:

• if you suspect or have had a hepatitis B virus infection. In a few cases, patients who have had hepatitis B may have a recurrence of the infection, with potentially fatal consequences. In patients with a history of hepatitis B, the doctor will closely monitor for signs of active hepatitis.

Before starting treatment with Bortezomib, you should carefully read the package leaflets of all medicines you are taking at the same time to get information about them. If you are taking thalidomide, you must exclude pregnancy and then use effective contraception (see section Pregnancy and Breastfeeding).

Children and Adolescents

Bortezomib should not be used in children and adolescents because its effects in this age group are unknown.

Bortezomib and Other Medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription.

In particular, you should inform your doctor if you are taking medicines containing any of the following active substances:

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

Pregnancy and Breastfeeding

Bortezomib should not be used during pregnancy unless it is absolutely necessary.

Both men and women taking Bortezomib must use effective contraception during treatment and for 3 months after treatment is completed. If, despite contraception, you become pregnant, you should immediately inform your doctor.

You should not breastfeed while taking Bortezomib.

You should discuss with your doctor a safe time to resume breastfeeding after treatment is completed.

Thalidomide can cause birth defects and fetal death. When taking Bortezomib in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see the thalidomide package leaflet).

Driving and Using Machines

Bortezomib may cause fatigue, dizziness, fainting, or blurred vision.

If you experience any of these symptoms, you should not drive or operate machinery.

You should be cautious, even if you do not experience any symptoms.

3. How to Use Bortezomib

Your doctor will determine the appropriate dose of Bortezomib based on your height and weight (body surface area).

The usual starting dose of Bortezomib is 1.3 mg/m² body surface area, administered twice a week.

Your doctor may adjust the dose and total number of treatment cycles based on your response to treatment, the occurrence of certain side effects, and other conditions (such as liver function disorders).

Relapsed Multiple Myeloma

If Bortezomib is used as a single medicine, you will receive 4 doses of Bortezomib intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day rest period.

This 21-day period (3 weeks) is one treatment cycle. You may receive up to 8 cycles of treatment (24 weeks).

You may also receive Bortezomib in combination with pegylated liposomal doxorubicin or dexamethasone.

If Bortezomib is administered in combination with pegylated liposomal doxorubicin, you will receive Bortezomib intravenously or subcutaneously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² body surface area as an intravenous infusion on day 4 of the 21-day cycle, after Bortezomib administration.

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

If Bortezomib is administered in combination with dexamethasone, you will receive Bortezomib intravenously or subcutaneously during a 21-day treatment cycle, and dexamethasone will be administered orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib treatment cycle.

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

Previously Untreated Multiple Myeloma

If you have multiple myeloma and have not been treated before and do not qualify for hematopoietic stem cell transplantation, you will receive Bortezomib in combination with two other medicines: melphalan and prednisone.

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

• Cycles 1-4: Bortezomib TZF will be administered twice a week, on days 1, 4, 8, 11, 22, 25, 29, and 32.
• 25, 29, and 32.
• Cycles 5-9: Bortezomib TZF will be administered once a week, on days 1, 8, 22, and 29.

Both melphalan (9 mg/m² body surface area) and prednisone (60 mg/m² body surface area) will be administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

• 2, 3, and 4 of the first week of each cycle.

If you have multiple myeloma and have not been treated before and qualify for hematopoietic stem cell transplantation, you will receive Bortezomib intravenously or subcutaneously in combination with other medicines: dexamethasone or dexamethasone plus thalidomide, as induction treatment.

If Bortezomib is administered with dexamethasone, you will receive Bortezomib intravenously or subcutaneously during a 21-day cycle, and dexamethasone will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib treatment cycle.

You will receive 4 cycles (12 weeks).

If Bortezomib is administered with dexamethasone and thalidomide, the treatment cycle lasts 28 days (4 weeks).

Dexamethasone will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib treatment cycle, and thalidomide will be administered orally once daily at a dose of 50 mg until day 14 of the first cycle, and if the dose is tolerated, it will be increased to 100 mg on days 15-28. From the second cycle onwards, the dose may be increased to 200 mg per day. You may receive up to 6 cycles (24 weeks).

Previously Untreated Mantle Cell Lymphoma

If you have mantle cell lymphoma and have not been treated before, you will receive Bortezomib intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib will be administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without medication administration. One treatment cycle lasts 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines will be administered as intravenous infusions on day 1 of each 21-day Bortezomib cycle: rituximab at a dose of 375 mg/m² body surface area, cyclophosphamide at a dose of 750 mg/m² body surface area, and doxorubicin at a dose of 50 mg/m² body surface area.

Prednisone will be administered orally at a dose of 100 mg/m² body surface area on days 1, 2, 3, 4, and 5 of the Bortezomib treatment cycle.

How Bortezomib is Administered

Bortezomib is intended for intravenous or subcutaneous administration.

Bortezomib will be administered by a healthcare professional with experience in the use of cytotoxic medicines.

The Bortezomib powder must be dissolved before administration. The medicine will be prepared by a healthcare professional.

The prepared solution will then be injected into a vein or under the skin.

Intravenous injection is rapid, lasting 3 to 5 seconds. Subcutaneous injection is administered into the thigh or abdomen.

Overdose of Bortezomib

Since this medicine is administered by a doctor or nurse, it is unlikely that an overdose will occur.

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

4. Possible Side Effects

Like all medicines, Bortezomib can cause side effects, although not everybody gets them.

Some of these side effects may be serious.

If you are receiving Bortezomib for multiple myeloma or mantle cell lymphoma, you should immediately tell your doctor if you experience any of the following symptoms:

• painful muscle spasms, muscle weakness;
• confusion, vision loss or disturbances, blindness, seizures, headaches;
• shortness of breath, swelling of the feet or changes in heart rhythm, high blood pressure, fatigue, fainting;
• cough and difficulty breathing or chest pressure.

The use of 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 have regular blood tests before and during treatment with Bortezomib to regularly check your blood cell count.

You may experience a decrease in:

• platelets, which can increase the risk of bruising or bleeding without visible injury (e.g., gastrointestinal bleeding, bleeding from the mouth, gums, or brain);
• red blood cells, which can lead to anemia with symptoms such as fatigue and paleness;
• white blood cells, which can increase the risk of infections or flu-like symptoms.

If you are receiving Bortezomib for multiple myeloma, you may experience the following side effects:

Very Common Side Effects (May Affect More Than 1 in 10 People):

• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in the hands or feet due to nerve damage;
• decrease in the number of red and (or) white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation, which may be severe and accompanied by bloating (may be severe);
• diarrhea: if it occurs, you should drink more water than usual, and your doctor may recommend taking additional medicines to control diarrhea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

Common Side Effects (May Affect Up to 1 in 10 People):

• low blood pressure, sudden drop in blood pressure when standing up, which can lead to fainting;
• high blood pressure;
• kidney function disorders;
• headache;
• general malaise, pain, dizziness of peripheral origin, lightheadedness, feeling of weakness or loss of consciousness;
• chills;
• infections, including pneumonia, respiratory tract infections, bronchitis, fungal infections, cough with sputum production, flu-like symptoms;
• shingles (localized around the eyes or widespread on the body);
• chest pain, shortness of breath during exercise;
• various types of rash;
• itching, skin nodules or dry skin;
• flushing of the face or broken blood vessels;
• redness of the skin;
• dehydration;
• heartburn, bloating, belching, gas, abdominal pain, gastrointestinal bleeding;
• liver function disorders;
• mouth or lip inflammation, dry mouth, mouth ulcers or throat pain; weight loss, loss of taste;
• painful muscle spasms, muscle spasms, muscle weakness, bone pain;
• blurred vision;
• infection of the outer layer of the eye (cornea) and the mucous membrane lining the eyelids (conjunctivitis);
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depression, restlessness or agitation, changes in mental state, disorientation;
• swelling, including around the eyes and other parts of the body.

Uncommon Side Effects (May Affect Up to 1 in 100 People):

• heart failure, heart attack, chest pain, feeling of discomfort in the chest, rapid or slow heart rate;
• kidney failure;
• vein inflammation, blood clots in veins and lungs;
• blood clotting disorders;
• circulatory failure;
• inflammation of the sac around the heart (pericarditis) or fluid in the pericardium;
• infections, including urinary tract infections, flu, viral infections, ear and soft tissue infections;
• bleeding in the gut or stomach;
• brain vessel disorders;
• paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, tremors, muscle tremors;
• joint inflammation, including joint inflammation of the fingers, toes, and jaw;
• lung disorders that make breathing difficult. Some of these include difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing;
• hiccups, speech disorders;
• increased or decreased urine production (due to kidney damage), painful urination, or blood/protein in the urine, fluid retention;
• consciousness disorders, confusion, worsening or loss of memory;
• allergic reactions;
• hearing loss, deafness, ringing or discomfort in the ears;
• hormonal disorders that can affect salt and water absorption;
• hyperthyroidism;
• insulin deficiency or insulin resistance;
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, stye (hordeolum), eyelid redness and swelling, eye discharge, vision disturbances, bleeding in the eyes;
• lymph node enlargement;
• joint stiffness or muscle stiffness, feeling of heaviness, groin pain;
• hair loss and abnormal hair structure;
• allergic reactions;
• redness or pain at the injection site;
• mouth pain;
• mouth or throat infection, mouth ulcers, esophagus, stomach, or intestine inflammation, sometimes with accompanying pain and bleeding, poor intestinal motility (including intestinal obstruction), abdominal discomfort, and esophageal discomfort, difficulty swallowing;
• skin infection;
• bacterial and viral infections;
• tooth infection;
• pancreatitis, bile duct obstruction;
• genital pain, erectile dysfunction;
• weight gain;
• thirst;
• hepatitis;
• injection site or catheter-related reactions and disorders;
• skin reactions and disorders (which can be severe and life-threatening), skin ulcers;
• bruising, falls, and injuries;
• inflammation or bleeding of blood vessels in the form of small red or purple spots (usually on the legs) to large, bruise-like spots under the skin;
• mild cysts;
• severe reversible brain disorders, including seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disturbances.

Rare Side Effects (May Affect Up to 1 in 1000 People):

• heart disease, including heart attack, angina pectoris;
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome);
• sudden flushing of the face;
• vein discoloration;
• spinal cord inflammation;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• altered or abnormal bowel function;
• brain bleeding;
• jaundice (yellowing of the skin and eyes);
• stye (hordeolum), eyelid redness and swelling;
• severe allergic reaction (anaphylactic shock) with symptoms such as difficulty breathing, chest pain or tightness, and dizziness or fainting, severe itching of the skin or hives, facial, lip, tongue, or throat swelling, which can cause difficulty swallowing, collapse;
• breast disorders;
• vaginal ulceration;
• genital swelling;
• alcohol intolerance;
• weight loss or gain;
• increased appetite;
• fistula;
• joint effusion;
• ganglion cyst (a type of cyst that forms on the joint membrane);
• bone fractures;
• muscle fiber breakdown leading to further complications;
• liver swelling, liver bleeding;
• kidney cancer;
• skin changes similar to psoriasis;
• skin cancer;
• skin pallor;
• increased platelet count or plasma cells (a type of white blood cell);
• blood clots in small blood vessels (microangiopathic thrombosis);
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• excessive salivation;
• exophthalmos;
• photophobia;
• rapid breathing;
• rectal pain;
• gallstones;
• hernia;
• injuries;
• brittle or weak nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulcers;
• multi-organ failure;
• death.

If you are receiving Bortezomib in combination with other medicines for mantle cell lymphoma, you may experience the following side effects:

Very Common Side Effects (May Affect More Than 1 in 10 People):

• pneumonia;
• loss of appetite;
• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in the hands or feet due to nerve damage;
• nausea or vomiting;
• diarrhea;
• mouth ulcers;
• constipation;
• muscle pain, bone pain;
• hair loss and abnormal hair structure;
• fatigue, feeling of weakness;
• fever.

Common Side Effects (May Affect Up to 1 in 10 People):

• shingles (localized around the eyes or widespread on the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, cough with sputum production, flu-like symptoms;
• fungal infections;
• allergic reactions;
• insulin deficiency or insulin resistance;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• consciousness disorders, confusion;
• dizziness;
• rapid heart rate, high blood pressure, increased sweating;
• abnormal or blurred vision;
• heart failure, heart attack, chest pain, feeling of discomfort in the chest, rapid or slow heart rate;
• high or low blood pressure;
• sudden drop in blood pressure when standing up, which can lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• gastrointestinal bleeding;
• heartburn;
• stomach pain;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth or lip inflammation, throat pain;
• liver function changes;
• itching;
• redness;
• rash;
• muscle spasms;
• urinary tract infections;
• bone pain;
• swelling, including around the eyes and other parts of the body;
• chills;
• redness and pain at the injection site;
• general malaise;
• weight loss;
• weight gain.

Uncommon Side Effects (May Affect Up to 1 in 100 People):

• hepatitis;
• severe allergic reaction (anaphylactic reaction), which can cause symptoms such as difficulty breathing, chest pain or tightness, and dizziness or fainting, severe itching of the skin or hives, facial, lip, tongue, or throat swelling, which can cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle tremors;
• peripheral dizziness;
• hearing loss, deafness;
• lung disorders that make breathing difficult. Some of these include difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing;
• pulmonary embolism;
• jaundice (yellowing of the skin and eyes);
• stye (hordeolum), eyelid redness and swelling.

Rare Side Effects (May Affect Up to 1 in 1000 People):

• blood clots in small blood vessels (microangiopathic thrombosis).

Reporting of Side Effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

Al. Jerozolimskie 181C, 02-222 Warsaw

Tel.: +48 22 49 21 301

Fax: +48 22 49 21 309

Website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to Store Bortezomib

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 vial label and carton after "EXP".

The batch number is the lot number.

There are no special storage instructions for this medicine.

Store the vial in the outer packaging to protect from light.

Prepared Solution

It has been demonstrated that the prepared solution is chemically and physically stable for 8 hours at 25°C in both the vial and syringe. For microbiological reasons, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user. Do not store in the refrigerator.

There is no need to protect the prepared solution from light.

6. Contents of the Pack and Other Information

What Bortezomib Contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as boronate ester with mannitol).
• The other ingredient is mannitol (E 421).

Intravenous Solution:

After reconstitution, 1 mL of the intravenous solution contains 1 mg of bortezomib.

Subcutaneous Solution:

After reconstitution, 1 mL of the subcutaneous solution contains 2.5 mg of bortezomib.

What Bortezomib Looks Like and Contents of the Pack

Bortezomib powder for solution for injection is a white or off-white lyophilized powder or powder.

Each pack contains 1 vial for single use.

Marketing Authorization Holder and Manufacturer

Tarchomińskie Zakłady Farmaceutyczne "Polfa" S.A.

ul. A. Fleminga 2

03-176 Warsaw

Tel.: (22) 811 18 14

For further information about this medicine, please contact the marketing authorization holder.

Date of Last Revision of the Leaflet

Information Intended for Healthcare Professionals Only:

1. Preparation of the Solution for Injection

Caution: Bortezomib is a cytotoxic medicine. When handling the medicine and preparing it for use, caution should be exercised. To protect the skin from contact with the medicine, gloves and protective clothing are recommended.

Bortezomib TZF does not contain preservatives, so it is essential to follow strict aseptic techniques when handling the medicine.

• 1.1. Preparation of the 3.5 mg vial: to the vial of Bortezomib, add 3.5 mL of sterile sodium chloride 9 mg/mL (0.9%) solution for injection, using an appropriate syringe, without removing the vial stopper. Reconstitution of the lyophilized powder takes less than 2 minutes.

The resulting solution will have a concentration of 1 mg/mL. After reconstitution, the solution will be clear and colorless, with a pH between 4 and 7. There is no need to check the pH of the solution.

• 1.2. Before administration, check the solution for any visible particles or change in color. If any change in color or precipitation is observed, the solution should be discarded. Ensure that the correct dose is administered intravenously (1 mg/mL).
• 1.3. The prepared solution has been shown to be chemically and physically stable for 8 hours at 25°C in both the vial and syringe. For microbiological reasons, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user. Do not store in the refrigerator.

There is no need to protect the prepared solution from light.

2. Administration

• After reconstitution, withdraw the appropriate dose of the prepared solution based on the calculated dose according to the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (check that the syringe is labeled as for intravenous use).
• Administer the solution as an intravenous bolus injection over 3 to 5 seconds through a central or peripheral intravenous catheter.
• Flush the intravenous catheter with a small amount of sterile sodium chloride 9 mg/mL (0.9%) solution for injection after administering Bortezomib.

Bortezomib is Intended for Intravenous or Subcutaneous Administration. Do Not Administer by Any Other Route. Intrathecal Administration Has Resulted in Death.

3. Disposal of the Medicine

The vial is for single use only, and any remaining solution should be discarded.

Any unused medicine or waste material should be disposed of in accordance with local regulations.

The following information is intended for healthcare professionals only:

Only the 3.5 mg vial can be used for subcutaneous administration, as described below.

Preparation of the Solution for Subcutaneous Injection

Caution: Bortezomib is a cytotoxic medicine. When handling the medicine and preparing it for use, caution should be exercised. To protect the skin from contact with the medicine, gloves and protective clothing are recommended.

Bortezomib TZF does not contain preservatives, so it is essential to follow strict aseptic techniques when handling the medicine.

• 1.1. Preparation of the 3.5 mg vial: to the vial of Bortezomib TZF, add 1.4 mL of sterile sodium chloride 9 mg/mL (0.9%) solution for injection, using an appropriate syringe, without removing the vial stopper. Reconstitution of the lyophilized powder takes less than 2 minutes.

The resulting solution will have a concentration of 2.5 mg/mL. After reconstitution, the solution will be clear and colorless, with a pH between 4 and 7. There is no need to check the pH of the solution.

• 1.2. Before administration, check the solution for any visible particles or change in color. If any change in color or precipitation is observed, the solution should be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/mL).
• 1.3. The prepared solution has been shown to be chemically and physically stable for 8 hours at 25°C in both the vial and syringe. For microbiological reasons, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user. Do not store in the refrigerator.

There is no need to protect the prepared solution from light.

2. Administration

• After reconstitution, withdraw the appropriate dose of the prepared solution based on the calculated dose according to the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (check that the syringe is labeled as for subcutaneous use).
• Administer the solution subcutaneously at an angle of 45-90°.
• Administer the prepared solution subcutaneously into the thigh (right or left) or abdomen (right or left side).
• Rotate the injection sites.
• If a local reaction occurs after subcutaneous injection of Bortezomib, the solution may be administered subcutaneously at a lower concentration (dilution to 1 mg/mL instead of 2.5 mg/mL) or the route of administration may be changed to intravenous.

Bortezomib is Intended for Intravenous or Subcutaneous Administration. Do Not Administer by Any Other Route. Intrathecal Administration Has Resulted in Death.

3. Disposal of the Medicine

The vial is for single use only, and any remaining solution should be discarded.

Any unused medicine or waste material should be disposed of in accordance with local regulations.