Bortezomib Zentiva

Patient Information Leaflet: User Information

Bortezomib Zentiva, 3.5 mg, powder for solution for injection

Bortezomib

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Bortezomib Zentiva and what is it used for
• 2. Important information before using Bortezomib Zentiva
• 3. How to use Bortezomib Zentiva
• 4. Possible side effects
• 5. How to store Bortezomib Zentiva
• 6. Package contents and other information

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

Bortezomib Zentiva contains the active substance bortezomib, which is a so-called "proteasome inhibitor". Proteasomes play a crucial role in controlling cell function and development. By disrupting their function, bortezomib can lead to the death of cancer cells.
Bortezomib Zentiva is used to treat multiple myeloma (a bone marrow cancer) in patients aged 18 and over:

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

Bortezomib Zentiva 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 rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not been previously treated and do not qualify for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Zentiva

When not to use Bortezomib Zentiva

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

Warnings and precautions

Before starting treatment with Bortezomib Zentiva, the patient should discuss with their doctor if they:

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

The patient must have regular blood tests before and during treatment with Bortezomib Zentiva to regularly check the number of blood cells.
If the patient is taking Bortezomib Zentiva in combination with rituximab, they should tell their doctor:

• if they suspect or have had hepatitis B virus infection in the past. In a few cases, patients who had hepatitis B virus infection had recurring episodes of hepatitis, which could be fatal. If the patient has a history of hepatitis B virus infection, they will be closely monitored by their doctor for signs of active hepatitis B virus infection.

Before starting treatment with Bortezomib Zentiva, the patient should carefully read the leaflets of all medicinal products they are taking during treatment to obtain information about them.
If the patient is taking thalidomide, they must exclude pregnancy and then use effective contraception (see section Pregnancy and breastfeeding).

Children and adolescents

Bortezomib Zentiva should not be used in children and adolescents, as it is not known how the medicine works in this age group.

Bortezomib Zentiva and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
In particular, the patient should inform their doctor if they are taking medicines containing any of the following active substances:

• ketokonazole, 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 drugs.

Pregnancy and breastfeeding

Bortezomib Zentiva should not be used during pregnancy, unless it is absolutely necessary.
Both men and women receiving Bortezomib Zentiva must use effective contraception during and for 3 months after completing treatment. If, despite using these methods, the patient becomes pregnant, they should immediately inform their doctor.
Women should not breastfeed during treatment with Bortezomib Zentiva. It is necessary to discuss with the doctor the safe time to return to breastfeeding after completing treatment.
Thalidomide causes birth defects and fetal death. When Bortezomib Zentiva is used in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and using machines

Bortezomib Zentiva may cause fatigue, dizziness, fainting, and blurred vision. If these symptoms occur, the patient should not drive or operate tools or machines; even if symptoms do not occur, caution should still be exercised.

3. How to use Bortezomib Zentiva

The doctor will adjust the appropriate dose of Bortezomib Zentiva for the patient based on their height and weight (body surface area). The most commonly used initial dose of Bortezomib Zentiva is 1.3 mg/m² administered twice a week.
The doctor may change the dose and total number of treatment cycles depending on the patient's response to treatment, the occurrence of side effects, and additional diseases (e.g., liver disease).
Relapsed multiple myeloma
If Bortezomib Zentiva is administered as a single drug, the patient will receive 4 doses of Bortezomib Zentiva intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day break in treatment. The described 21-day period (3 weeks) is considered one treatment cycle.
The patient will receive up to 8 cycles (24 weeks).
The patient may also receive Bortezomib Zentiva in combination with pegylated liposomal doxorubicin or dexamethasone.

• When Bortezomib Zentiva is administered in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Zentiva intravenously or subcutaneously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² by intravenous infusion after Bortezomib Zentiva injection on day 4 of the 21-day cycle.
• The patient may receive up to 8 cycles (24 weeks).
• When Bortezomib Zentiva is administered in combination with dexamethasone, the patient will receive Bortezomib Zentiva 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 Bortezomib Zentiva treatment cycle.
• The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If the patient has not been previously treated for multiple myeloma and does notqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Zentiva in combination with melphalan and prednisone.
In this case, the treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1-4, Bortezomib Zentiva is administered twice a week, on days 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5-9, Bortezomib Zentiva is administered once a week, on days 1, 8, 22, and 29. Both melphalan (9 mg/m²) and prednisone (60 mg/m²) are administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If the patient has not been previously treated for multiple myeloma and doesqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Zentiva intravenously or subcutaneously in combination with dexamethasone or dexamethasone with thalidomide for induction treatment.
When Bortezomib Zentiva is administered with dexamethasone, the patient will receive Bortezomib Zentiva 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 Zentiva treatment cycle.
The patient will receive up to 4 cycles (12 weeks).
When Bortezomib Zentiva 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 Zentiva treatment cycle, and thalidomide will be administered orally once a day at a dose of 50 mg up to day 14 of the first cycle, and if the dose is tolerated, it will be increased to 100 mg from days 15-28 and may be further increased to 200 mg per day from the second cycle.
The patient may receive up to 6 cycles (24 weeks).
Previously untreated mantle cell lymphoma
If the patient has not been previously treated for mantle cell lymphoma, they will receive Bortezomib Zentiva intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib Zentiva will be administered intravenously on days 1, 4, 8, and 11, followed by a "rest period" without medication administration. One treatment cycle lasts 21 days (3 weeks). The patient will receive up to 8 cycles (24 weeks).
The following drugs will be administered as intravenous infusions on day 1 of each 21-day Bortezomib Zentiva cycle:

• Rituximab at a dose of 375 mg/m²;
• Cyclophosphamide at a dose of 750 mg/m²;
• Doxorubicin at a dose of 50 mg/m².

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

How Bortezomib Zentiva is administered

This medicine is administered intravenously or subcutaneously. Bortezomib Zentiva will be administered by a healthcare professional with experience in the use of cytotoxic drugs.
The powder of Bortezomib Zentiva must be dissolved before administration. The preparation of the medicine is carried out by a healthcare professional. The resulting solution is then injected either rapidly intravenously over 3 to 5 seconds or subcutaneously. The subcutaneous injection is administered into the thigh or abdomen.

Overdose of Bortezomib Zentiva

Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive too much of the medicine.
If this happens, the doctor will monitor the patient for any side effects.

4. Possible side effects

Like all medicines, Bortezomib Zentiva can cause side effects, although not everybody gets them.
Some of these side effects can be serious.
If the patient is receiving Bortezomib Zentiva for multiple myeloma or mantle cell lymphoma, they should immediately tell their doctor if they experience any of the following symptoms:

• muscle cramps, muscle weakness;
• confusion, loss of vision, 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 tightness.

Treatment with Bortezomib Zentiva can very often cause a decrease in the number of red and white blood cells and platelets in the patient's blood. Therefore, the patient must have regular blood tests before and during treatment with Bortezomib Zentiva to regularly check the number of blood cells. The patient may experience a decrease in:

• platelet count, which can lead to a tendency to bruise or bleed without injury (e.g., gastrointestinal bleeding, bleeding from the mouth, or brain hemorrhage);
• red blood cell count, which can lead to anemia, characterized by symptoms such as fatigue and pallor;
• white blood cell count, which can lead to increased susceptibility to infections or the occurrence of flu-like symptoms.

If the patient is receiving Bortezomib Zentiva for multiple myeloma, they may experience the following side effects:

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

• hypersensitivity, 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;
• diarrhea: if this occurs, the patient should drink more water than usual, and the doctor may recommend taking additional medications to control diarrhea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

Common side effects(may affect less than 1 in 10 people):

• low blood pressure, sudden drop in blood pressure when standing up, which can lead to fainting;
• high blood pressure;
• decreased kidney function;
• headache;
• general feeling of being unwell, pain, dizziness, 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, e.g., around the eyes, or widespread on the body);
• chest pain, shortness of breath during exercise;
• various types of rash;
• itching, skin lumps 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;
• muscle spasms, muscle weakness, bone pain;
• blurred vision;
• infection of the outer layer of the eye and the inner surface of the eyelid (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 less than 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 surrounding the heart (pericarditis) or fluid in the pericardium;
• infections, including urinary tract infections, flu, herpes, ear and soft tissue infections;
• bleeding from the gastrointestinal tract or stomach;
• nerve damage;
• paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, 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;
• blood clots in small blood vessels (microangiopathic thrombosis);
• jaundice (yellowing of the skin and eyes);
• serious 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, swelling of the face, lips, tongue, and throat, which can cause difficulty breathing and swallowing, shock;
• breast disorders;
• vaginal ulcers;
• genital swelling;
• intolerance to alcohol;
• weight loss or gain;
• increased thirst;
• hepatitis;
• complications at the injection site or related to the use of a venous catheter;
• skin reactions (which can be severe and life-threatening), skin ulcers;
• bruises, falls, and injuries;
• inflammation or bleeding of blood vessels, which can cause small red or purple spots (usually on the legs) to large bruise-like spots under the skin;
• benign cysts;
• severe reversible brain disorders, which can include seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disorders.

Rare side effects(may affect less than 1 in 1000 people):

• heart disease, including heart attack, angina pectoris;
• flushing;
• discoloration of veins;
• inflammation of the spinal cord;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• abnormal or changed bowel function;
• brain bleeding;
• jaundice (yellowing of the skin and eyes);
• serious 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, swelling of the face, lips, tongue, and throat, which can cause difficulty breathing and swallowing, shock;
• breast disorders;
• vaginal ulcers;
• genital swelling;
• intolerance to alcohol;
• weight loss or gain;
• increased thirst;
• hepatitis;
• complications at the injection site or related to the use of a venous catheter;
• skin reactions (which can be severe and life-threatening), skin ulcers;
• bruises, falls, and injuries;
• inflammation or bleeding of blood vessels, which can cause small red or purple spots (usually on the legs) to large bruise-like spots under the skin;
• benign cysts;
• severe reversible brain disorders, which can include seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disorders;
• joint effusion;
• ganglion cyst (a cyst that forms on the tendon sheath);
• bone fractures;
• muscle fiber breakdown leading to further complications;
• liver swelling, liver bleeding;
• kidney cancer;
• a skin condition similar to psoriasis;
• skin cancer;
• pallor;
• increased platelet count or plasma cells (a type of white blood cell);
• blood clots in small blood vessels (microangiopathic thrombosis);
• adverse reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• excessive salivation;
• exophthalmos;
• photophobia;
• increased respiratory rate;
• rectal pain;
• gallstones;
• hernia;
• injuries;
• brittle or weak nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulcers;
• multi-organ failure;
• death;
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).

If the patient is receiving Bortezomib Zentiva in combination with other medicines for mantle cell lymphoma, they may experience the following side effects:

• Very common side effects(may affect more than 1 in 10 people):
• lung inflammation;
• loss of appetite;
• hypersensitivity, 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 less than 1 in 10 people):

• shingles (localized, e.g., around the eyes, or widespread on the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• decreased insulin production or resistance to normal insulin levels;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• changed level of consciousness, confusion;
• dizziness;
• rapid heartbeat, high blood pressure, sweating;
• abnormal or changed vision, 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 in the ears, ear discomfort;
• gastrointestinal bleeding;
• heartburn;
• abdominal pain, belching;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth or lip inflammation, throat pain;
• liver function changes;
• itching;
• redness of the skin;
• rash;
• muscle spasms;
• urinary tract infections;
• limb pain;
• swelling, including around the eyes and other parts of the body;
• chills;
• redness and pain at the injection site;
• general feeling of illness;
• weight loss or gain.

Uncommon side effects(may affect less than 1 in 100 people):

• hepatitis;
• serious 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, swelling of the face, lips, tongue, and throat, which can cause difficulty breathing and swallowing, shock;
• movement disorders, paralysis, tremors;
• 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;
• blood clots in the lungs;
• jaundice (yellowing of the skin and eyes);
• ganglion cyst (a cyst that forms on the tendon sheath).

Reporting side effects

If side effects occur, including those not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products of the Office for Registration of Medicinal Products.
Al. Jerozolimskie 181 C, 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 or its representative in Poland. By reporting side effects, more information can be collected on the safety of the medicine.

• The above information is intended for medical professionals only.

5. How to store Bortezomib Zentiva

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and outer packaging, after "Expiry Date (EXP)".
Store the vial in the outer packaging to protect it from light.
There are no special storage temperature requirements for the medicine.
Diluted solution
From a microbiological point of view, the diluted solution should be used immediately after preparation. If not used immediately, the user is responsible for the storage time and conditions of the diluted solution. The chemical and physical stability of the diluted solution is maintained for 8 days at 25°C, 60% relative humidity, or 15 days at 5±3°C, when stored in the dark, both in the vial and in a polypropylene syringe.

6. Package contents and other information

What Bortezomib Zentiva contains

• The active substance of the medicine is bortezomib. Each vial contains 3.5 mg of bortezomib (as a mannitol and boric acid ester).
• The other ingredients are mannitol (E 421).

Intravenous solution for injection:
After dissolution, 1 ml of the solution for injection contains 1 mg of bortezomib.
Subcutaneous solution for injection:
After dissolution, 1 ml of the solution for injection contains 2.5 mg of bortezomib.

What Bortezomib Zentiva looks like and contents of the pack

Bortezomib Zentiva powder for solution for injection is a white or off-white lyophilized powder or powder.
Bortezomib Zentiva 3.5 mg is available in glass vials with a bromobutyl rubber stopper and an aluminum seal with a plastic flip-off cap, in a cardboard box.
Each pack contains 1 vial for single use.
Marketing authorization holder
Zentiva, k.s.
U Kabelovny 130, 102 37 Prague 10, Czech Republic
Manufacturer
Synthon Hispania SL, Castelló 1101, Las Salinas, Barcelona, 08830, Spain; Synthon s.r.o., Blansko, Brnenska 32/c.p.597, 678 01 Blansko, Czech Republic

For more detailed information on the medicine and its names in the Member States of the European Economic Area, please contact the representative of the marketing authorization holder in Poland:

Zentiva Polska Sp. z o.o., ul. Bonifraterska 17, 00-203 Warsaw, tel.: +48 22 375 92 00
Date of last revision of the leaflet:February 2021

The following information is intended for healthcare professionals only:

1. Preparation of the solution for intravenous injection

Caution: Bortezomib Zentiva is a cytotoxic product. When handling the medicine and preparing it for use, caution should be exercised. To protect against skin contact with the medicine, the use of gloves and other protective clothing is recommended.
Since Bortezomib Zentiva does not contain preservatives, strict aseptic techniques must be followed when handling the medicine.

• 1.1. Preparation of the 3.5 mg vial: add 3.5 ml of sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib Zentiva powder. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. After dissolution, 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, visually inspect the solution for particulate matter and discoloration. If particulate matter or discoloration is observed, the solution should be discarded. Ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3. The reconstituted solution is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution is maintained for 8 days at 25°C, 60% relative humidity, or 15 days at 5±3°C, when stored in the dark, both in the vial and in a polypropylene syringe. If the diluted solution is not used immediately, the user is responsible for the storage time and conditions of the solution before administration.

2. Administration

• After reconstitution, withdraw the appropriate volume of the reconstituted solution based on the dose calculated from the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (ensure that the syringe is labeled for intravenous administration).
• Administer the solution as an intravenous bolus over 3 to 5 seconds.
• Flush the intravenous administration line with a small amount of sterile, 9 mg/ml (0.9%) sodium chloride solution for injection.

Bortezomib Zentiva 3.5 mg, powder for solution for injection is administered intravenouslyor subcutaneously. 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.
Dispose of any unused product or waste material in accordance with local requirements.

The following information is intended for healthcare professionals only:

1. Preparation of the solution for subcutaneous injection

Caution: Bortezomib Zentiva is a cytotoxic product. When handling the medicine and preparing it for use, caution should be exercised. To protect against skin contact with the medicine, the use of gloves and other protective clothing is recommended.
Since Bortezomib Zentiva does not contain preservatives, strict aseptic techniques must be followed when handling the medicine.

• 1.1. Preparation of the 3.5 mg vial: add 1.4 ml of sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib Zentiva powder. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 2.5 mg/ml. After dissolution, 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, visually inspect the solution for particulate matter and discoloration. If particulate matter or discoloration is observed, the solution should be discarded. Ensure that the correct dose is administered subcutaneously(2.5 mg/ml).
• 1.3. The reconstituted solution is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution is maintained for 8 days at 25°C, 60% relative humidity, or 15 days at 5±3°C, when stored in the dark, both in the vial and in a polypropylene syringe. If the diluted solution is not used immediately, the user is responsible for the storage time and conditions of the solution before administration.

2. Administration

• After reconstitution, withdraw the appropriate volume of the reconstituted solution based on the dose calculated from the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (ensure that the syringe is labeled for subcutaneous administration).
• 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 Zentiva, it is recommended to administer the solution subcutaneously at a lower concentration (dilution to 1 mg/ml instead of 2.5 mg/ml) or to switch to intravenous administration.

Bortezomib Zentiva powder for solution for injection 3.5 mg is administered intravenouslyor subcutaneously. 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.
Dispose of any unused product or waste material in accordance with local requirements.