Bortezomib zentiva

Bortezomib Zentiva, 3.5 mg, powder for solution for injection
Bortezomib

Please read the following information carefully before using this medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Bortezomib Zentiva is and what it is 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. Contents of the pack and other information

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

Bortezomib Zentiva contains an active substance called bortezomib, which is a so-called
"proteasome inhibitor". Proteasomes play a key role in regulating cell functions and their
development process. By interfering with their function, bortezomib may lead to the death of
cancer cells.

Bortezomib Zentiva is used in the treatment of multiple myeloma (a cancer of the bone marrow)
in patients aged 18 years and older:

• as monotherapy or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone, in patients whose disease has progressed after at least one prior therapy and who are either not candidates for or have had a failed autologous hematopoietic stem cell transplantation;
• in combination with melphalan and prednisone, in previously untreated patients who are not eligible for high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation;
• in combination with dexamethasone or with dexamethasone and thalidomide, in previously untreated patients who are eligible for high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (induction therapy).

Bortezomib Zentiva is also used in the treatment of mantle cell lymphoma (a type of cancer
affecting the lymph nodes) in patients aged 18 years and older, in combination with
rituximab, cyclophosphamide, doxorubicin, and prednisone, in those who have not been previously treated and who are not eligible for autologous 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 particularly severe lung or heart diseases.

Warnings and precautions
Before starting treatment with Bortezomib Zentiva, discuss with the doctor if the patient:

• has a low number of red or white blood cells;
• has bleeding disorders and/or a low platelet count;
• has diarrhoea, constipation, nausea or vomiting;
• has previously experienced fainting, dizziness or lightheadedness;
• has kidney diseases;
• has moderate to severe liver function disorders;
• has previously experienced numbness, tingling or pain in hands and feet (neuropathy symptoms);
• has heart diseases or problems with blood pressure;
• has shortness of breath or cough;
• has seizures;
• has shingles (around the eyes or disseminated throughout the body);
• has tumour lysis syndrome symptoms such as muscle cramps, muscle weakness, confusion, vision loss or breathing difficulties;
• experiences memory loss, thinking disorders, difficulty walking or vision loss. These may be symptoms of a severe brain infection and the doctor may recommend further tests and monitoring.

Regular blood tests must be performed before and during treatment with Bortezomib Zentiva to monitor blood cell counts regularly.
If the patient has mantle cell lymphoma and is receiving Bortezomib Zentiva together with a medicine containing rituximab, inform the doctor:

• if the patient suspects a hepatitis virus infection or has had it in the past. In some cases, patients who had hepatitis B virus (HBV) infection have experienced recurrent episodes of hepatitis, which could be fatal. If the patient has a history of HBV infection, the doctor will closely monitor for symptoms of active HBV.

Before starting treatment with Bortezomib Zentiva, carefully read the package leaflets of all medicinal products being taken during treatment to obtain information about them.
If thalidomide is being taken, pregnancy must be excluded and effective contraception must be used (see section Pregnancy and breastfeeding).
Children and adolescents
Bortezomib Zentiva should not be used in children and adolescents, as the effect of the medicine in this group is unknown.
Bortezomib Zentiva and other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
In particular, inform the treating doctor if the patient is 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 Zentiva must not be used during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib Zentiva must use effective contraception during treatment and for 3 months after treatment has ended. If a woman becomes pregnant despite using these methods, she must inform her doctor immediately.
Women must not breastfeed during treatment with Bortezomib Zentiva. The timing of safe return to breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes birth defects and fetal death. When Bortezomib Zentiva is used in combination with thalidomide, patients must comply with the requirements of the "Thalidomide Pregnancy Prevention Programme" (see the thalidomide package leaflet).
Driving and using machines
Bortezomib Zentiva may cause fatigue, dizziness, fainting and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Even if no symptoms are present, caution should still be exercised.

3. How to use Bortezomib Zentiva

The treating physician will adjust the appropriate dose of Bortezomib Zentiva according to the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib Zentiva is 1.3 mg/m² of body surface area administered twice weekly.
The physician may modify the dose and the total number of treatment cycles depending on the patient's response to treatment, occurrence of adverse reactions, and additional medical conditions (e.g. liver disease).

Multiples myeloma
If Bortezomib Zentiva is administered as a single agent, the patient will receive 4 doses of Bortezomib Zentiva intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day treatment break. This 21-day period (3 weeks) is considered one treatment cycle. The patient may 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 together 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 as an 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 together 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 21-day 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 the patient does not qualify for hematopoietic stem cell transplantation, the patient will receive Bortezomib Zentiva in combination with melphalan and prednisone.

In this case, each treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1–4, Bortezomib Zentiva is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5–9, Bortezomib Zentiva is administered once weekly 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 the patient qualifies for hematopoietic stem cell transplantation, the patient will receive Bortezomib Zentiva intravenously or subcutaneously in combination with dexamethasone or with dexamethasone and thalidomide as induction therapy.

When Bortezomib Zentiva is administered with dexamethasone, the patient will receive Bortezomib Zentiva intravenously or subcutaneously in 21-day cycles, and dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 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 at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 28-day Bortezomib Zentiva treatment cycle. Thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle; if this dose is tolerated, it is increased to 100 mg from days 15 to 28, and may subsequently be increased to 200 mg daily starting 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, the patient will receive Bortezomib Zentiva intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Zentiva is administered intravenously on days 1, 4, 8, and 11, followed by a "rest period" without treatment. Each treatment cycle lasts 21 days (3 weeks). The patient may receive up to 8 cycles (24 weeks).

The following drugs are 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, and doxorubicin at a dose of 50 mg/m².

Prednisone is 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 used exclusively by intravenous or subcutaneous route. Bortezomib Zentiva will be administered by trained medical personnel experienced in handling cytotoxic drugs.

The Bortezomib Zentiva powder must be reconstituted before administration. The reconstitution is performed by trained medical personnel. The prepared solution is then administered either as a rapid intravenous injection over 3 to 5 seconds or subcutaneously. Subcutaneous injection is given in the thigh or abdomen.

Administration of a higher than recommended dose of Bortezomib Zentiva
Since this medicine is administered by a physician or nurse, it is highly unlikely that the patient will receive an overdose.
However, if this occurs exceptionally, the physician will monitor the patient for any adverse reactions.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Some of these side effects may be serious.
If the patient is receiving Bortezomib Zentiva for the treatment of multiple myeloma or mantle cell lymphoma, inform the doctor immediately if any of the following symptoms occur:

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

Treatment with Bortezomib Zentiva may very commonly lead to a reduction in the number of red and white blood cells and platelets in the patient's blood. Therefore, blood tests must be performed frequently before and during treatment with Bortezomib Zentiva to monitor blood cell counts regularly. The patient may experience a decrease in:

• platelets, which may lead to a tendency to bruise or bleed without injury (e.g., bleeding from the intestines, stomach, mouth and gums, or hemorrhage in the brain or liver);
• red blood cells, which may lead to anaemia, with symptoms such as fatigue and pallor;
• white blood cells, which may increase susceptibility to infections or cause flu-like symptoms.

If the patient is receiving Bortezomib Zentiva for the treatment of multiple myeloma, they may
experience the following side effects:
Very common side effects (may occur in more than 1 in 10 people):

• hypersensitivity, numbness, tingling or burning sensation of the skin, pain in hands or feet due to nerve damage;
• decreased number of red and (or) white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation, with or without abdominal distension (symptoms may be severe);
• diarrhoea: if it occurs, the patient must drink more fluids than usual; the doctor may recommend additional medicines to control diarrhoea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

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

• low blood pressure, sudden drop in blood pressure upon standing, which may lead to fainting;
• high blood pressure;
• reduced 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, flu-like symptoms;
• shingles (localized, e.g., around the eyes, or disseminated throughout the body);
• chest pain, shortness of breath during physical exercise;
• various types of skin rash;
• itchy skin, skin nodules or dry skin;
• facial flushing or capillary rupture;
• skin redness;
• dehydration;
• heartburn, bloating, belching, flatulence, abdominal pain, bleeding from the intestine or stomach;
• liver function abnormalities;
• inflammation of the mouth or lips, dry mouth, mouth ulcers or sore throat;
• weight loss, loss of taste;
• muscle cramps, muscle weakness, limb pain;
• blurred vision;
• infection of the outer layer of the eye and inner eyelid surface (conjunctivitis);
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, changes in mental state, disorientation;
• swelling, including around the eyes and other parts of the body.

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

• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate;
• kidney failure;
• phlebitis, blood clots in veins and lungs;
• blood clotting disorders;
• circulatory failure;
• pericarditis (inflammation of the outer lining of the heart) or fluid in the pericardium;
• infections including: urinary tract infections, influenza, herpes, ear infection, connective tissue infection;
• blood in stool, mucosal bleeding, e.g., from the mouth or vagina;
• cerebral vascular disorders;
• paralysis, seizures, falls, movement disorders, abnormal, altered or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, twitching;
• arthritis, including arthritis of fingers, toes and jaw;
• lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or respiratory arrest, wheezing;
• hiccups, speech disorders;
• increased or decreased urine production (due to kidney damage), painful urination or blood/protein in urine, fluid retention;
• altered level of consciousness, confusion, worsening or loss of memory;
• hypersensitivity;
• hearing loss, deafness, ringing or discomfort in the ears;
• hormonal disorders affecting salt and water absorption;
• hyperthyroidism;
• insufficient insulin production or resistance to normal insulin levels;
• eye irritation or inflammation, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid nodule (stye), eyelid redness and swelling, eye discharge, vision disturbances, eye bleeding;
• enlarged lymph nodes;
• joint 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;
• infection or inflammation of the mouth, oesophagus, stomach and intestines, sometimes with associated pain and bleeding, impaired intestinal peristalsis (including obstruction), abdominal and oesophageal discomfort, difficulty swallowing, vomiting blood;
• skin infection;
• bacterial and viral infections;
• dental infections;
• pancreatitis, biliary duct obstruction;
• genital organ pain, erectile dysfunction;
• weight gain;
• thirst;
• hepatitis;
• injection site reactions or complications related to vascular catheter use;
• skin reactions and disorders (which may be severe and life-threatening), skin ulceration;
• bruising, falls and injuries;
• inflammation or bleeding of blood vessels manifesting as small red or purple spots (usually on legs) up to large bruise-like subcutaneous patches;
• benign cysts;
• severe reversible encephalopathy syndrome including seizures, high blood pressure, headache, fatigue, confusion, blindness or other visual disturbances.

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

• heart diseases including heart attack, angina pectoris;
• flushing attacks;
• vein discoloration;
• spinal cord inflammation;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of hepatic veins);
• altered or abnormal intestinal function;
• brain haemorrhage;
• yellowing of eyes or skin (jaundice);
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, pain or tightness in the chest, and (or) dizziness/fainting, severe skin itching or raised skin lumps, swelling of face, lips, tongue and (or) throat which may cause difficulty breathing and swallowing, collapse;
• breast disorders;
• vaginal ulceration;
• genital swelling;
• alcohol intolerance;
• wasting or weight loss;
• increased appetite;
• fistula;
• joint effusion;
• synovial cyst (ganglion cyst);
• bone fractures;
• rhabdomyolysis leading to further complications;
• liver swelling, liver bleeding;
• kidney cancer;
• skin condition resembling psoriasis;
• skin cancer;
• skin pallor;
• increased number of platelets or plasma cells (a type of white blood cell);
• blood clot in small blood vessels (thrombotic microangiopathy);
• abnormal reaction to blood transfusion;
• partial or complete vision loss;
• decreased libido;
• drooling;
• eye protrusion;
• photophobia;
• increased respiratory rate;
• anal pain;
• gallstones;
• hernia;
• cuts;
• brittle or weak nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulceration;
• multi-organ failure;
• death;
• severe nerve inflammation which may cause paralysis and breathing difficulties (Guillain-Barré syndrome).

If the patient is receiving Bortezomib Zentiva in combination with other medicines for the treatment of mantle cell lymphoma, they may experience the following side effects:
Very common side effects (may occur in more than 1 in 10 people):

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

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

• shingles (localized, e.g., around the eyes, or disseminated throughout the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• insufficient insulin production or resistance to normal insulin levels;
• fluid retention;
• sleep disturbances;
• loss of consciousness;
• altered level of consciousness, confusion;
• dizziness;
• rapid heartbeat, high blood pressure, sweating;
• visual disturbances, blurred vision;
• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate;
• high or low blood pressure;
• sudden drop in blood pressure upon changing position which may lead to fainting;
• shortness of breath during exertion;
• cough;
• hiccups;
• ringing in the ears, ear discomfort;
• bleeding from the intestine or stomach;
• heartburn;
• abdominal pain, belching;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• inflammation or ulceration of the mouth or lips, sore throat;
• altered liver function;
• itchy skin;
• skin redness;
• rash;
• muscle cramps;
• urinary tract infections;
• limb pain;
• swelling affecting eyes and other body parts;
• chills;
• redness and pain at the injection site;
• general feeling of illness;
• weight loss;
• weight gain.

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

• hepatitis;
• severe allergic reaction (anaphylactic reaction), symptoms of which may include: difficulty breathing, chest pain or tightness, dizziness or fainting, severe skin itching or blisters, swelling of face, lips, tongue, throat, which may cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle twitching;
• dizziness;
• hearing loss, deafness;
• lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or respiratory arrest, wheezing;
• blood clots in the lungs;
• jaundice (yellowing of skin and eyes);
• eyelid nodule (stye), eyelid redness and swelling.

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

• blood clot in small blood vessels (thrombotic microangiopathy).

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform the doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.
Al. Jerozolimskie 181 C
02 - 222 Warsaw
Tel.: + 48 22 49 21 301
Faks: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting side effects helps to provide more information on the safety of this medicine.

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,
following "Expiry date (EXP)".
Store the vial in the outer packaging to protect it from light.
There are no special requirements regarding storage temperature.
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.
The solution has been shown to be chemically and physically stable for 8 days at 25°C and 60% relative humidity,
or for 15 days at 5±3°C, stored in a place protected from light, both in the vial and in a polypropylene syringe.

6. Contents of the pack and other information

What Bortezomib Zentiva contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol ester and boric acid).
• Other ingredients: mannitol (E 421).

Intravenous injection solution:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Subcutaneous injection solution:
After reconstitution, 1 ml of subcutaneous injection solution 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 almost white, compacted powder or powder.
Bortezomib Zentiva 3.5 mg is available in glass vials with a bromobutyl rubber stopper, aluminium seal and plastic flip-off cap, packed in a cardboard box.
Each pack contains 1 single-use vial.

Marketing Authorisation 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 further information about this medicinal product and its names in the European Economic Area countries, please contact the representative of the marketing authorisation holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00

The following information is intended for healthcare professionals only:

1. PREPARATION OF INTRAVENOUS INJECTION SOLUTION
Warning: Bortezomib Zentiva is a cytotoxic agent. Exercise caution when handling and preparing the medicinal product. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE BORTEZOMIB ZENTIVA DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.

1.1. Reconstitution of the 3.5 mg vial: add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib Zentiva powder. Dissolution of the lyophilised 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 colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.

1.2. Visually inspect the solution before administration to ensure it is free from particles and discolouration. If particles or discolouration are observed, the solution must be discarded. Check the concentration on the vial to ensure the correct dose is administered intravenously (1 mg/ml).

1.3. The reconstituted product is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for 8 days at 25°C and 60% relative humidity, or for 15 days at 5±3°C when stored protected from light, both in the vial and in a polypropylene syringe. If the diluted solution is not administered immediately after preparation, the person administering the medicinal product to the patient is responsible for the storage time and conditions prior to use.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicinal product in the syringe (check whether the syringe is labelled for intravenous administration).
• Inject the solution as an intravenous bolus over 3 to 5 seconds through a centrally or peripherally inserted intravenous catheter.
• The intravenous catheter used for administration should be flushed with a small volume of sterile 9 mg/ml (0.9%) sodium chloride injection solution.

Bortezomib Zentiva 3.5 mg, powder for solution for injection, IS ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL OF THE MEDICINAL PRODUCT
The vial is for single use only, and any unused solution must be discarded.
Any unused product or waste material must be disposed of in accordance with local regulations.

The following information is intended for healthcare professionals only:
Only the 3.5 mg vial may be used for subcutaneous administration, as described below.

1. PREPARATION OF SUBCUTANEOUS INJECTION SOLUTION
Warning: Bortezomib Zentiva is a cytotoxic agent. Exercise caution when handling and preparing the medicinal product. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE BORTEZOMIB ZENTIVA DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.

1.1. Reconstitution of the 3.5 mg vial: add 1.4 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib Zentiva powder. Dissolution of the lyophilised 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 colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.

1.2. Visually inspect the solution before administration to ensure it is free from particles and discolouration. If particles or discolouration are observed, the solution must be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).

1.3. The reconstituted product is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for 8 days at 25°C and 60% relative humidity, or for 15 days at 5±3°C when stored protected from light, both in the vial and in a polypropylene syringe. If the diluted solution is not administered immediately after preparation, the person administering the medicinal product to the patient is responsible for the storage time and conditions prior to use.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicinal product in the syringe (check whether the syringe is labelled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The prepared solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left side).
• Rotate injection sites for subsequent injections.
• In case of local reactions after subcutaneous administration of Bortezomib Zentiva, it is recommended to administer a less concentrated subcutaneous solution of Bortezomib Zentiva (diluted to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous administration.

Bortezomib Zentiva, powder for solution for injection, 3.5 mg dose, IS ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL OF THE MEDICINAL PRODUCT
The vial is for single use only, and any unused solution must be discarded.
Any unused product or waste material must be disposed of in accordance with local regulations.