Bortezomib msn

Package leaflet: Information for the patient

Bortezomib MSN, 3.5 mg, powder for solution for injection
Bortezomib
Please read all of this leaflet carefully before use, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Bortezomib MSN is and what it is used for
2. Important information before using Bortezomib MSN
3. How to use Bortezomib MSN
4. Possible side effects
5. How to store Bortezomib MSN
6. Contents of the pack and other information

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

Bortezomib MSN contains an active substance called bortezomib, which is a so-called
proteasome inhibitor. Proteasomes play an important role in controlling cell functions and their
development process. By interfering with their function, bortezomib may lead to the death of
cancer cells.
Bortezomib MSN is used in the treatment of multiple myeloma (a cancer of the bone marrow) in
patients aged at least 18 years:

• as monotherapy or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone, in patients whose disease has progressed (progressive disease) after at least one prior therapy and in whom haematopoietic stem cell transplantation has failed or is not possible;
• in combination with melphalan and prednisone, in previously untreated patients who are not eligible for high-dose chemotherapy with haematopoietic stem cell transplantation;
• in combination with dexamethasone or dexamethasone with thalidomide, in previously untreated patients who are eligible for high-dose chemotherapy with haematopoietic stem cell transplantation (induction therapy).

Bortezomib MSN is used in the treatment of mantle cell lymphoma (a type of cancer
affecting the lymph nodes) in patients aged at least 18 years, in combination with the medicines:
rituximab, cyclophosphamide, doxorubicin and prednisone, in previously untreated patients who are not eligible for haematopoietic stem cell transplantation.

2. Important information before using Bortezomib MSN
When not to use Bortezomib MSN

• If the patient is allergic to bortezomib 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
Please inform your doctor if the patient:

• has low numbers of red or white blood cells;
• has bleeding disorders and/or 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 impairment;
• has previously experienced numbness, tingling or pain in hands and feet (neuropathy symptoms);
• has heart diseases or blood pressure problems;
• 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;
• has memory loss, thinking disorders, difficulty walking or vision loss. These may be symptoms of a severe brain infection, and your doctor may recommend further tests and monitoring.

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

• if the patient suspects a hepatitis virus infection or has had it in the past. In some cases, patients with hepatitis B virus (HBV) infection have experienced reactivation of hepatitis, which could be fatal. If the patient has a history of HBV infection, they will be closely monitored by the doctor for signs of active HBV.

Before starting treatment with Bortezomib MSN, please read carefully the leaflets of all
medicinal products used during treatment to obtain information about them. If thalidomide is
used, pregnancy must be excluded and effective contraception must be used (see section Pregnancy and breastfeeding).

Children and adolescents
Bortezomib MSN must not be used in children and adolescents, as its effects in this patient group are unknown.

Bortezomib MSN and other medicines
Please tell your doctor about all medicines currently used, recently used, or planned to be used.
In particular, inform your 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 in epilepsy treatment;
• St John's wort (Hypericum perforatum), used for depression and other conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding
Do not use Bortezomib MSN during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib MSN must use effective contraception during treatment and for 3 months after treatment ends. If pregnancy occurs despite these measures, inform your doctor immediately.
Women must not breastfeed during treatment with Bortezomib MSN. The timing of safe resumption of breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes birth defects and fetal death. When Bortezomib MSN 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 MSN may cause fatigue, dizziness, fainting and blurred vision. If such symptoms occur, do not drive or operate tools or machinery. Even if no symptoms are present, caution should still be exercised.

3. How to use Bortezomib MSN
Your doctor will determine the appropriate dose of Bortezomib MSN based on the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib MSN is 1.3 mg/m² body surface area administered twice weekly.
Your doctor may adjust the dose and total number of treatment cycles depending on the patient's response to treatment, occurrence of side effects and additional conditions (e.g. liver function).

Relapsed multiple myeloma
If Bortezomib MSN is administered as monotherapy, the patient will receive 4 doses of Bortezomib MSN 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 will receive up to 8 cycles (24 weeks).
The patient may also receive Bortezomib MSN in combination with: pegylated liposomal doxorubicin or dexamethasone.
When Bortezomib MSN is administered with pegylated liposomal doxorubicin, the patient will receive Bortezomib MSN 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 MSN injection on day 4 of the 21-day cycle.
The patient may receive up to 8 cycles (24 weeks).
When Bortezomib MSN is administered with dexamethasone, the patient will receive Bortezomib MSN 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 MSN 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 is not eligible for haematopoietic stem cell transplantation, they will receive Bortezomib MSN in combination with other medicines: melphalan and prednisone.
In this case, the treatment cycle duration is 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1–4, Bortezomib MSN is administered twice weekly on days: 1, 4, 8, 11, 22, 25, 29 and 32.
• During cycles 5–9, Bortezomib MSN 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 is eligible for haematopoietic stem cell transplantation, they will receive Bortezomib MSN intravenously or subcutaneously in combination with other medicines: dexamethasone or dexamethasone with thalidomide, as induction therapy.
When Bortezomib MSN is administered with dexamethasone, the patient will receive Bortezomib MSN intravenously or subcutaneously in a 21-day cycle, and dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day Bortezomib MSN treatment cycle. The patient will receive up to 4 cycles (12 weeks).
When Bortezomib MSN is administered with dexamethasone and thalidomide, the treatment cycle duration is 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 the 28-day Bortezomib MSN treatment cycle, and thalidomide is administered orally once daily at a dose of 50 mg until day 14 of the first cycle; if tolerated, the dose is increased to 100 mg from days 15 to 28, and may be further increased to 200 mg daily from the second cycle onwards. 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 intravenous Bortezomib MSN in combination with the medicines: rituximab, cyclophosphamide, doxorubicin and prednisone.
Bortezomib MSN is administered intravenously on days 1, 4, 8 and 11, followed by a "rest period" without treatment. One treatment cycle lasts 21 days (3 weeks). The patient will receive up to 8 cycles (24 weeks).
The following medicines are administered as intravenous infusions on day 1 of each 21-day Bortezomib MSN treatment cycle: rituximab at a dose of 375 mg/m², cyclophosphamide at a dose of 750 mg/m² and doxorubicin at a dose of 50 mg/m².
Prednisone is administered orally at a dose of 100 mg/m² on days 1, 2, 3, 4 and 5 of the Bortezomib MSN treatment cycle.

How Bortezomib MSN is administered
This medicine is administered intravenously or subcutaneously. Bortezomib MSN will be administered by medical personnel experienced in handling cytotoxic medicines.
The Bortezomib MSN powder must be reconstituted before administration. Preparation is performed by trained medical personnel. The resulting solution is then administered either as a rapid intravenous injection over 3 to 5 seconds or subcutaneously. Subcutaneous injection is administered into the thigh or abdomen.

Overdose of Bortezomib MSN
Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive too high a dose. If, exceptionally, this occurs, the doctor will monitor the patient for any side effects.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
These reactions are usually mild or moderate.
If the patient is receiving Bortezomib MSN for the treatment of multiple myeloma or mantle cell lymphoma, inform the doctor immediately if the patient experiences any of the following symptoms:

• 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 MSN may very commonly cause 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 MSN to regularly monitor blood cell counts. The patient may experience a reduction in:

• platelets, which may lead to a tendency to bruise or bleeding not caused by injury (e.g.: gastrointestinal or gastric bleeding, bleeding from mouth and gums, or intracranial or hepatic haemorrhage);
• red blood cells, which may lead to anaemia, associated with symptoms such as fatigue and pallor;
• white blood cells, which may lead to increased susceptibility to infections or flu-like symptoms.

If the patient is receiving Bortezomib MSN for the treatment of multiple myeloma, the following adverse reactions may occur:
Very common adverse reactions (may affect 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 bloating (symptoms may be severe);
• diarrhoea: if this occurs, the patient must drink more fluids than usual; the doctor may recommend taking additional medicines to control diarrhoea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

Common adverse reactions (may affect up to 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 production, flu-like symptoms;
• shingles (localized, e.g., around the eyes or disseminated over the body);
• chest pain, shortness of breath during physical exercise;
• various types of skin rashes;
• 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 disorders;
• 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;
• conjunctivitis;
• nosebleeds;
• difficulty falling asleep, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, changes in mental state, disorientation;
• oedema, including around the eyes and in other parts of the body.

Uncommon adverse reactions (may affect up to 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 coagulation 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 and 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 making breathing difficult. 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 output (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 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 (hordeolum), red and swollen eyelids, 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, mouth ulcers, oesophagus, stomach and intestinal ulcers, sometimes with associated pain and bleeding, weak 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 the use of a vascular catheter;
• skin reactions and disorders (which may be severe and life-threatening), skin ulceration;
• bruising, falls and injuries;
• vascular inflammation or bleeding manifesting as small red or purple spots (usually on legs) 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 adverse reactions (may affect up to 1 in 1000 people):

• heart diseases including heart attack, angina pectoris;
• flushing attacks;
• vein discoloration;
• spinal cord inflammation;
• ear diseases, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by hepatic vein obstruction);
• altered or abnormal intestinal function;
• brain haemorrhage;
• yellowing of eyes or skin (jaundice);
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, chest pain or tightness, 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 diseases;
• vaginal ulceration;
• genital oedema;
• alcohol intolerance;
• wasting or weight loss;
• increased appetite;
• fistula;
• joint effusion;
• synovial cyst (ganglion cyst);
• bone fractures;
• rhabdomyolysis leading to further complications;
• liver oedema, liver bleeding;
• kidney cancer;
• psoriasis-like skin condition;
• skin cancer;
• skin pallor;
• increased number of platelets or plasma cells (a type of white blood cell);
• blood clots in small blood vessels (thrombotic microangiopathy);
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• drooling;
• exophthalmos;
• 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 lead to paralysis and breathing difficulties (Guillain-Barré syndrome).

If the patient is receiving Bortezomib MSN in combination with other medicines for the treatment of mantle cell lymphoma, the following adverse reactions may occur:
Very common adverse reactions (may affect 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 adverse reactions (may affect up to 1 in 10 people):

• shingles (localized, e.g., around the eyes or disseminated over 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;
• abnormal vision, 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 intestine;
• abdominal pain;
• inflammation of the mouth or lips, sore throat;
• altered liver function;
• skin itching;
• skin redness;
• rash;
• muscle cramps;
• urinary tract infection;
• limb pain;
• oedema affecting eyes and other body parts;
• chills;
• redness and pain at the injection site;
• general feeling of illness;
• weight loss;
• weight gain.

Uncommon adverse reactions (may affect up to 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 making breathing difficult. 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 (hordeolum), red and swollen eyelids.

Rare adverse reactions (may affect up to 1 in 1000 people):

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

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. Adverse reactions 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 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder. Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Bortezomib MSN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial label after:
Expiry date (EXP). The expiry date refers to the last day of the stated month.
There are no special requirements regarding storage temperature. Store the vial in the original
packaging to protect from light.
The prepared solution remains chemically and physically stable for 8 hours at 25°C if stored in the
original vial and (or) syringe. From a microbiological point of view, unless the reconstitution method excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, the responsibility for the duration and conditions of storage prior to administration lies with the user.
The medicinal product Bortezomib MSN is intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

What Bortezomib MSN contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as a boronic acid ester with mannitol).
• The other ingredient is: mannitol.

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 MSN looks like and contents of the pack
Bortezomib MSN is a white or almost white lyophilised powder or powder.
Each carton of Bortezomib MSN contains a 10 ml glass vial with a blue cap.

Marketing Authorisation Holder:
Vivanta Generics s.r.o.
Třtinová 260/1, Čakovice
196 00 Prague 9
Czech Republic

Importer:
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA3000
Malta

This medicinal product is authorised for marketing in the European Economic Area under the following names:
Finland Bortezomib MSN
Czech Republic Bortezomib MSN
Hungary Bortezomib MSN
Poland Bortezomib MSN
Romania Bortezomib MSN 3.5 mg powder for solution for injection

Information intended exclusively for healthcare professionals:

1. PREPARATION OF INTRAVENOUS INJECTION SOLUTION
Warning: Bortezomib MSN is a cytotoxic product. Therefore, caution must be taken when handling Bortezomib MSN medicinal product and during its preparation for use. To avoid skin contact, use of gloves and protective clothing is recommended.
WHEN HANDLING BORTEZOMIB MSN MEDICINAL PRODUCT, STRICT ASEPTIC TECHNIQUES MUST BE FOLLOWED, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

1.1. Reconstitution of the 3.5 mg vial: carefully add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib MSN powder, using an appropriate syringe without removing the vial stopper. The lyophilised powder dissolves in less than 2 minutes.
The concentration of the resulting solution will be 1 mg/ml. The reconstituted solution will be clear and colourless, with a final 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 undissolved particles or discolouration. If any change in colour or presence of solid particles is observed, the prepared solution must be discarded. Ensure that the correct dose is administered intravenously (1 mg/ml).

1.3. The prepared solution is preservative-free and should be used immediately after reconstitution. However, chemical and physical stability has been demonstrated for up to 8 hours when stored at 25°C in the original vial and/or syringe. The total storage time of the medicinal product after reconstitution before administration should not exceed 8 hours. If the solution is not used immediately, the user is responsible for the storage period and conditions.

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 solution in the syringe (check that the syringe is labelled for intravenous administration).
• Inject the medicinal product solution as an intravenous bolus over 3 to 5 seconds through a centrally or peripherally placed intravenous catheter.
• The intravenous catheter used for administration should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride injection solution.

Medicinal product Bortezomib MSN 3.5 mg, powder for solution for injection
IS ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. Do not administer by any other route. Intrathecal administration has resulted in death.

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

The following information is intended exclusively for healthcare professionals:
Only the 3.5 mg vial may be administered subcutaneously, as described below.

1. PREPARATION OF SUBCUTANEOUS INJECTION SOLUTION
Warning: Bortezomib MSN is a cytotoxic product. Therefore, caution must be taken when handling Bortezomib MSN medicinal product and during its preparation for use. To avoid skin contact, use of gloves and protective clothing is recommended.
WHEN HANDLING BORTEZOMIB MSN MEDICINAL PRODUCT, STRICT ASEPTIC TECHNIQUES MUST BE FOLLOWED, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

1.1. Reconstitution of the 3.5 mg vial: carefully add 1.4 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib MSN powder, using an appropriate syringe without removing the vial stopper. The lyophilised powder dissolves in less than 2 minutes.
The concentration of the resulting solution will be 2.5 mg/ml. The reconstituted 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. Before administration, visually inspect the solution for undissolved particles or discolouration. If any change in colour or presence of solid particles is observed, the prepared solution must be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).

1.3. The prepared solution is preservative-free and should be used immediately after reconstitution. However, chemical and physical stability has been demonstrated for up to 8 hours when stored at 25°C in the original vial and/or syringe. The total storage time of the medicinal product after reconstitution before administration should not exceed 8 hours. If the solution is not used immediately, the user is responsible for the storage period and conditions.

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 solution in the syringe (check that the syringe is labelled for subcutaneous administration).
• Inject the medicinal product solution subcutaneously at an angle of 45–90°.
• The prepared solution is administered subcutaneously into the thigh (right or left) or abdomen (right or left side).
• Injection sites should be rotated with subsequent injections.
• In case of local reaction after subcutaneous administration of Bortezomib MSN, it is recommended to administer a more diluted solution of Bortezomib MSN (diluted to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous administration.

Medicinal product Bortezomib MSN 3.5 mg, powder for solution for injection
IS ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. Do not administer by any other route. Intrathecal administration has resulted in death.

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