Bortezomib Msn

Package Leaflet: Information for the Patient

Bortezomib MSN, 3.5 mg, Powder for Solution for Injection

Bortezomib

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

• Keep this leaflet, as 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, inform the doctor or pharmacist. See section 4.

Table of Contents of the Leaflet:

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

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

Bortezomib MSN 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 MSN is used to treat multiple myeloma (a type of bone marrow cancer) in patients aged 18 and over:

• as a single medicine or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone in patients whose disease has progressed after at least one previous treatment and for whom hematopoietic stem cell transplantation was not successful or not possible;
• in combination with melphalan and prednisone in patients who have not been 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 MSN 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 taking Bortezomib MSN

When not to take 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 severe lung or heart disease.

Warnings and precautions

Inform the treating doctor if the patient:

• has a low number of red or white blood cells;
• has bleeding disorders and (or) a low platelet count;
• experiences diarrhea, constipation, nausea, or vomiting;
• has a history of fainting, dizziness, and blurred vision;
• has kidney disease;
• has moderate to severe liver function disorders;
• has a history of numbness, tingling, and pain in the hands and feet (symptoms of neuropathy);
• has heart disease or blood pressure problems;
• has shortness of breath or cough;
• experiences seizures;
• has shingles (around the eyes or widespread on the body);
• experiences symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, loss of vision, and shortness of breath;
• 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 observation.

The patient must undergo regular blood tests before and during treatment with Bortezomib MSN to regularly check the blood cell count.
If the patient is taking Bortezomib MSN in combination with rituximab, inform the doctor:

• if the patient suspects or has had hepatitis B virus infection in the past. In a few cases, patients who had hepatitis B virus infection may have 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 the doctor for signs of active hepatitis B virus infection.

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

Children and adolescents

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

Bortezomib MSN and other medicines

Inform the doctor about all medicines currently taken or recently taken, as well as medicines planned to be taken.
In particular, inform the treating doctor if the patient is 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 for the treatment of epilepsy;
• St. John's Wort (Hypericum perforatum) for the treatment of depression and other conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding

Bortezomib MSN should not be taken during pregnancy, unless absolutely necessary.
Both men and women taking Bortezomib MSN must use effective contraceptive methods during and up to 3 months after completing treatment. If, despite the use of these methods, the patient becomes pregnant, inform the doctor immediately.
Patients should not breastfeed during treatment with Bortezomib MSN. It is necessary to discuss with the doctor the safe timing of returning to breastfeeding after completing treatment in the patient.
Thalidomide causes birth defects and fetal death. When taking Bortezomib MSN in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide package leaflet).

Driving and using machines

Bortezomib MSN may cause fatigue, dizziness, fainting, and blurred vision. In case of such symptoms, do not drive vehicles or operate tools or equipment; even if symptoms do not occur, caution should still be exercised.

3. How to take Bortezomib MSN

The treating doctor will adjust the appropriate dose of Bortezomib MSN for the patient based on the patient's height and weight (body surface area). The most commonly used initial dose of Bortezomib MSN 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).
Progressive multiple myeloma
If Bortezomib MSN is administered as a single medicine, the patient will receive 4 doses of Bortezomib MSN 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 MSN in combination with pegylated liposomal doxorubicin or dexamethasone.

• During cycles 1-4, Bortezomib MSN is administered twice a week, on days: 1, 4, 8, 11,
• 22, 25, 29, and 32.
• During cycles 5-9, Bortezomib MSN 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.

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

If the patient has not been previously treated for multiple myeloma and the patientqualifies for hematopoietic stem cell transplantation, they will receive Bortezomib MSN intravenously or subcutaneously in combination with dexamethasone or dexamethasone with thalidomide for induction treatment.
In the case where 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 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day treatment cycle with Bortezomib MSN. The patient may receive up to 4 cycles (12 weeks).
In the case where Bortezomib MSN 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 the 28-day treatment cycle with Bortezomib MSN, 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 on 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 MSN intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib MSN is 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 may receive up to 8 cycles (24 weeks).
The following medicines are administered as intravenous infusions on day 1 of each 21-day treatment cycle with Bortezomib MSN: 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 treatment cycle with Bortezomib MSN.

How Bortezomib MSN is administered

This medicine is administered intravenously or subcutaneously. Bortezomib MSN will be administered by medical personnel experienced in the use of cytotoxic medicines.
Bortezomib MSN in the form of powder must be dissolved before administration. The preparation of the medicine is carried out by medical personnel. The prepared solution is then injected either quickly intravenously, over 3 to 5 seconds, or subcutaneously. The 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 much of the medicine. If this happens, the doctor will monitor the patient for side effects.

4. Possible side effects

Like all medicines, Bortezomib MSN can cause side effects, although not everybody gets them.
These effects are usually mild or moderate.
If the patient is taking Bortezomib MSN for multiple myeloma or mantle cell lymphoma, inform the doctor immediately if the patient experiences the following symptoms:

• muscle cramps, muscle weakness;
• confusion, loss 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 pressure.

Treatment with Bortezomib MSN may 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 undergo regular blood tests before and during treatment with Bortezomib MSN to regularly check the blood cell count. The patient may experience a decrease in:

• platelet count, which may lead to a tendency to bruise or bleed without injury (e.g., gastrointestinal bleeding, bleeding from the mouth, gums, or nose);
• red blood cell count, which may lead to anemia, accompanied by symptoms such as fatigue and paleness;
• white blood cell count, which may lead to increased susceptibility to infections or flu-like symptoms.

If the patient is taking Bortezomib MSN 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 caused by nerve damage;
• decrease in the number of red and (or) white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation occurring with or without bloating (symptoms may be severe);
• diarrhea: if it occurs, the patient should drink more water than usual, and the doctor may recommend taking additional medicines to control diarrhea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

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

• low blood pressure, sudden drop in blood pressure when standing up, which may lead to fainting;
• high blood pressure;
• decreased kidney function;
• headache;
• general feeling of being unwell, pain, dizziness, blurred vision, 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 of the skin, skin nodules or dry skin;
• flushing of the face or broken blood vessels;
• redness of the skin;
• dehydration;
• heartburn, bloating, belching, gas, abdominal pain, gastrointestinal bleeding;
• liver function disorders;
• mouth or lip inflammation, dry mouth, mouth ulcers or throat pain;
• weight loss, loss of taste;
• muscle cramps, muscle weakness, limb pain;
• blurred vision;
• 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 affect up to 1 in 100 people):

• heart failure, heart attack, chest pain;
• flushing;
• discoloration of the veins;
• spinal cord inflammation;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• abnormal bowel movements;
• brain bleeding;
• jaundice (yellowing of the skin and eyes);
• stye (inflammation of the eyelid), red and swollen eyelids.

Rare side effects (may affect up to 1 in 1000 people):

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

Reporting side effects

If side effects occur, including those not listed in this leaflet, inform the doctor or pharmacist or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Bortezomib MSN

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the vial after EXP.
There are no special storage instructions for the medicine. Store the vial in its original packaging to protect from light.
The prepared solution is 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 precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.
Bortezomib MSN is for single use only. Any unused medicine or waste material should be disposed of in accordance with local requirements.

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 boronic acid ester with mannitol).
• The other ingredient is mannitol.

Injection solution for intravenous administration:
After reconstitution, 1 ml of injection solution contains 1 mg of bortezomib.
Injection solution for subcutaneous administration:
After reconstitution, 1 ml of injection solution contains 2.5 mg of bortezomib.

What Bortezomib MSN looks like and contents of the pack

Bortezomib MSN is a white or off-white lyophilized powder or powder.
Each carton of Bortezomib MSN contains a glass vial with a blue cap.

Marketing authorization 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 medicine is authorized in the Member States of 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

Date of last revision of the leaflet: 07/2022

Information intended for healthcare professionals only:

1. Preparation of the solution for intravenous injection

Caution: Bortezomib MSN is a cytotoxic product. Therefore, caution should be exercised when handling the medicinal product Bortezomib MSN and when preparing it for use. To avoid skin contact, gloves and protective clothing are recommended.
WHEN HANDLING THE MEDICINAL PRODUCT BORTEZOMIB MSN, STRICT ASEPTIC TECHNIQUE MUST BE FOLLOWED, AS IT DOES NOT CONTAIN PRESERVATIVES.

• 1.1. Preparation of the 3.5 mg vial: carefully add 3.5 mlof sterile, 9 mg/ml (0.9%) sodium chloride injection to the vial containing Bortezomib MSN powder, using an appropriate syringe, without removing the vial cap. Reconstitution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. The reconstituted solution will be clear and colorless, and its final pH will be 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 any change in color or presence of particulate matter is observed, the prepared solution should 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 preparation. However, chemical and physical stability has been demonstrated for 8 hours if the solution is stored at 25°C in the original vial and (or) syringe. The total storage time of the medicinal product after reconstitution, prior to administration, should not exceed 8 hours. If the solution is not used immediately, the storage times and conditions are the responsibility of the user.

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 prepared solution in the syringe (check if the syringe is labeled for intravenous administration).
• Administer the medicinal product solution by intravenous injection over 3 to 5 seconds (bolus) through a centrally or peripherally inserted intravenous catheter.
• The intravenous catheter through which the medicinal product was administered should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride injection.

Bortezomib MSN 3.5 mg, powder for solution for injection

ADMINISTER INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY ANY OTHER ROUTE. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. Disposal

The vial is for single use only, and any remaining solution should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.