Bortezomib medac

Package Leaflet: Information for the User

Bortezomib medac 1 mg powder for solution for intravenous injection

Bortezomib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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

Contents of the pack and other information

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

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

Bortezomib medac 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 medac is used to treat multiple myeloma (a type of bone marrow cancer) in adults aged 18 years or older:

• as a single medicine or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone in patients whose disease has progressed after at least one prior treatment and who have undergone a failed or are not eligible for hematopoietic stem cell transplantation;
• in combination with melphalan and prednisone in patients who have not received prior treatment and are not eligible for high-dose chemotherapy with hematopoietic stem cell transplantation;
• in combination with dexamethasone or dexamethasone with thalidomide for induction treatment in patients who have not received prior treatment and are eligible for high-dose chemotherapy with hematopoietic stem cell transplantation.

Bortezomib medac is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in adults aged 18 years or older, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not received prior treatment and are not eligible for hematopoietic stem cell transplantation.

2. What you need to know before you take Bortezomib medac

When not to take Bortezomib medac

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

if you have severe lung or heart disease.

• if you have severe lung or heart disease.

Warnings and precautions

Before starting treatment with Bortezomib medac, you should discuss with your doctor or pharmacist if you have any of the following conditions:

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

You will need to have regular blood tests before and during treatment with Bortezomib medac to check your blood cell count.

If you are taking Bortezomib medac in combination with rituximab for mantle cell lymphoma, you should tell your doctor:

• if you suspect you have a hepatitis B virus infection or have had it in the past. In a few cases, patients who had a hepatitis B infection had recurring episodes of hepatitis, which can be life-threatening. If you have a history of hepatitis B, your doctor will closely monitor you for signs of active hepatitis B.

Before starting treatment with Bortezomib medac, you should read the package leaflets of all the medicines you are taking during treatment to get information about them.

If you are taking thalidomide, you must exclude pregnancy and use effective contraception (see section "Pregnancy and breastfeeding").

Children and adolescents

Bortezomib medac should not be used in children and adolescents because its safety and efficacy in this age group have not been established.

Other medicines and Bortezomib medac

Tell your doctor or pharmacist about all the medicines you are taking, have recently taken, or might take.

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

• 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 medicines.

Pregnancy and breastfeeding

Do not take Bortezomib medac if you are pregnant or think you may be pregnant, unless it is absolutely necessary.

Women of childbearing age must use effective contraception during treatment and for 8 months after treatment.

If you want to freeze your eggs (oocytes) before starting treatment, you should discuss this with your doctor.

Men should not father a child during treatment with Bortezomib medac and should use effective contraception during treatment and for up to 5 months after treatment.

If you want to donate sperm before starting treatment, you should consult your doctor.

Do not breastfeed during treatment with Bortezomib medac.

You should discuss with your doctor when it is safe to resume breastfeeding after treatment.

Thalidomide can cause birth defects and fetal death.

When taking Bortezomib medac in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Programme" (see the thalidomide package leaflet).

Driving and using machines

Bortezomib medac may cause fatigue, dizziness, fainting, and blurred vision.

Do not drive or operate machinery if you experience these symptoms.

3. How to take Bortezomib medac

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

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

Your doctor may adjust the dose and total number of treatment cycles based on your response to treatment, side effects, and other conditions (e.g., liver disease).

Relapsed multiple myeloma

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

This 21-day period (3 weeks) is considered one treatment cycle.

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

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

When Bortezomib medac is given in combination with pegylated liposomal doxorubicin, you will receive Bortezomib medac intravenously during the 21-day treatment cycle, and pegylated liposomal doxorubicin will be given as an intravenous infusion at a dose of 30 mg/m² on day 4 of the 21-day cycle.

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

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

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

Untreated multiple myeloma

If you have not received prior treatment for multiple myeloma and are not eligible for hematopoietic stem cell transplantation, you will receive Bortezomib medac intravenously in combination with melphalan and prednisone.

The treatment cycle lasts 42 days (6 weeks).

You will receive 9 cycles (54 weeks).

• During cycles 1-4, Bortezomib medac will be given twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• 11, 22, 25, 29, and 32.
• During cycles 5-9, Bortezomib medac will be given once a week on days 1, 8, 22, and 29.

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

If you have not received prior treatment for multiple myeloma and are eligible for hematopoietic stem cell transplantation, you will receive Bortezomib medac intravenously in combination with dexamethasone or dexamethasone with thalidomide for induction treatment.

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

You may receive up to 4 cycles (12 weeks).

When Bortezomib medac is given in combination with dexamethasone and thalidomide, the treatment cycle lasts 28 days (4 weeks).

Dexamethasone will be given orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day treatment cycle, and thalidomide will be given orally once daily at a dose of 50 mg on day 14 of the first cycle, and the dose may be increased to 100 mg on days 15-28 and may be further increased to 200 mg daily from the second cycle.

You may receive up to 6 cycles (24 weeks).

Untreated mantle cell lymphoma

If you have not received prior treatment for mantle cell lymphoma, you will receive Bortezomib medac intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib medac will be given intravenously on days 1, 4, 8, and 11, followed by a rest period.

One treatment cycle lasts 21 days (3 weeks).

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

The following medicines will be given as intravenous infusions on day 1 of each 21-day 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 will be given orally at a dose of 100 mg/m² on days 1, 2, 3, 4, and 5 of the treatment cycle.

How Bortezomib medac is given

This medicine is given only by intravenous injection.

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

Bortezomib medac must be dissolved before administration.

The preparation of the medicine is carried out by a healthcare professional.

The resulting solution is then injected into a vein.

The injection into the vein is quick and takes 3 to 5 seconds.

Overdose

Since this medicine is given by a doctor or nurse, it is unlikely that you will receive too much.

If you do receive too much, your doctor will monitor you for side effects.

4. Possible side effects

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

Some of these side effects can be serious.

If you are taking Bortezomib medac for multiple myeloma or mantle cell lymphoma, you should tell your doctor immediately if you 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 pressure. Treatment with Bortezomib medac can very often cause a decrease in the number of red and white blood cells and platelets in the blood.
• platelet count, which can lead to bruising or bleeding that is not caused by injury (e.g., bleeding from the gut, stomach, mouth, and gums, or bleeding in the brain or liver);
• red blood cell count, which can lead to anemia, characterized by fatigue and paleness;
• white blood cell count, which can lead to increased susceptibility to infections or flu-like symptoms.

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

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

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

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

• low blood pressure, sudden drop in blood pressure when standing up, which can lead to fainting;
• high blood pressure;
• decreased kidney function;
• headache;
• general feeling of being unwell, pain, dizziness, lightheadedness, feeling weak 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);
• chest pain and shortness of breath during exercise;
• various types of rash;
• itching, redness, or dryness of the skin;
• flushing of the face or broken blood vessels;
• redness of the skin;
• dehydration;
• heartburn, bloating, belching, gas, abdominal pain, bleeding from the gut or stomach;
• liver function disorders;
• mouth ulcers or mouth pain, dry mouth, mouth infections;
• weight loss, loss of taste;
• muscle spasms, muscle weakness, bone pain;
• blurred vision;
• conjunctivitis;
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depression, restlessness, or agitation, changes in mental status, 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, discomfort in the chest, rapid or slow heart rate;
• kidney failure;
• blood clots in the 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 gut or stomach;
• nervous system disorders, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome);
• joint pain, including pain in the fingers, toes, and jaw;
• respiratory 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;
• ringing in the ears, discomfort in the ears;
• blood clots in the small blood vessels (microangiopathic hemolytic anemia);
• yellowing of the eyes or skin (jaundice);
• severe allergic reactions (anaphylactic reactions), which can cause difficulty breathing, chest pain or tightness, and dizziness or fainting;
• breast disorders;
• vaginal ulcers;
• genital swelling;
• intolerance to alcohol;
• weight loss or gain;
• increased appetite;
• fistula;
• joint effusion;
• ganglion cyst (a type of lump that forms under the skin);
• bone fractures;
• muscle fiber breakdown, which can lead to further complications;
• liver swelling or bleeding;
• kidney cancer;
• a skin condition similar to psoriasis;
• skin cancer;
• pale skin;
• increased platelet count or plasma cells (a type of white blood cell);
• blood clots in the small blood vessels (microangiopathic hemolytic anemia);
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• excessive salivation;
• bulging eyes;
• increased sensitivity to light;
• increased breathing rate;
• rectal pain;
• gallstones;
• hernia;
• brittle or weak nails;
• abnormal protein deposits in organs;
• coma;
• intestinal ulcers;
• multi-organ failure;
• death;
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).

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

• heart disorders, including heart attack, angina;
• flushing;
• discoloration of the veins;
• inflammation of the spinal cord;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (a condition that causes blockage of the hepatic veins);
• abnormal bowel movements;
• brain bleeding;
• yellowing of the eyes or skin (jaundice);
• severe allergic reactions (anaphylactic reactions), which can cause difficulty breathing, chest pain or tightness, and dizziness or fainting;
• breast disorders;
• vaginal ulcers;
• genital swelling;
• intolerance to alcohol;
• weight loss or gain;
• increased appetite;
• fistula;
• joint effusion;
• ganglion cyst (a type of lump that forms under the skin);
• bone fractures;
• muscle fiber breakdown, which can lead to further complications;
• liver swelling or bleeding;
• kidney cancer;
• a skin condition similar to psoriasis;
• skin cancer;
• pale skin;
• increased platelet count or plasma cells (a type of white blood cell);
• blood clots in the small blood vessels (microangiopathic hemolytic anemia);
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• excessive salivation;
• bulging eyes;
• increased sensitivity to light;
• increased breathing rate;
• rectal pain;
• gallstones;
• hernia;
• brittle or weak nails;
• abnormal protein deposits in organs;
• coma;
• intestinal ulcers;
• multi-organ failure;
• death;
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).

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

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

• pneumonia;
• loss of appetite;
• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in 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 weak;
• fever.

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

• shingles (localized, e.g., around the eyes, or widespread);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, cough with sputum production, flu-like symptoms;
• fungal infections;
• allergic reactions;
• decreased insulin production or insulin resistance;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• altered level of consciousness, confusion;
• dizziness;
• rapid or slow heart rate, 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 when standing up, which can lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing in the ears, discomfort in the ears;
• bleeding from the gut or stomach;
• heartburn;
• abdominal pain;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth ulcers or mouth pain, sore throat;
• liver function disorders;
• 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 being unwell;
• weight loss;
• weight gain.

Uncommon side effects(may affect up to 1 in 100 people):

• liver inflammation;
• severe allergic reactions (anaphylactic reactions), which can cause difficulty breathing, chest pain or tightness, and dizziness or fainting;
• movement disorders, paralysis, muscle tremors;
• dizziness;
• hearing loss, deafness;
• respiratory 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;
• yellowing of the eyes or skin (jaundice);
• sty (a type of lump that forms on the eyelid), redness and swelling of the eyelid.

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

• blood clots in the small blood vessels (microangiopathic hemolytic anemia).

Reporting of side effects

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

Side effects can be reported to the national reporting system via the website https://smz.ezdrowie.gov.pl.

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

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

5. How to store Bortezomib medac

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after "EXP".

Store the vial in the outer carton in order to protect from light.

No special storage instructions are required for this medicine.

Diluted solution

The chemical and physical stability of the diluted solution has been demonstrated for 8 days when stored at 25°C and 60% relative humidity or 15 days when stored at 5 ± 3°C in the dark, both in the vial and in a polypropylene syringe.

From a microbiological point of view, the product should be used immediately.

If not used immediately, the in-use storage times and conditions are the responsibility of the user.

Normally, the storage time would not exceed 24 hours at 2-8°C, unless the preparation and dilution have been carried out under controlled and validated aseptic conditions.

Bortezomib medac is for single use only.

Any unused product or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Bortezomib medac contains

• The active substance is bortezomib. Each vial contains 1 mg of bortezomib (as a boron ester with mannitol). After reconstitution, 1 ml of the solution for injection contains 1 mg of bortezomib.
• The other ingredient is mannitol (E 421).

What Bortezomib medac looks like and contents of the pack

Bortezomib medac is a white or almost white cake or powder.

Bortezomib medac is packed in a glass vial with a rubber stopper and a green flip-off cap.

Each pack contains 1 vial for single use.

Marketing authorization holder

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel: +49 4103 8006-0

Fax: +49 4103 8006-100

Manufacturer

Synthon s.r.o.

Brněnská 32/čp 597

678 01 Blansko

Czech Republic

Synthon Hispania, S.L.

C/ Castelló, n°1

Pol. Las Salinas, Sant Boi de Llobregat

08830 Barcelona

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Netherlands, Italy: Bortezomib medac

Date of last revision of the leaflet:04/2025

Information intended for healthcare professionals only:

1. Preparation of the solution for intravenous injection

Caution: Bortezomib medac is a cytotoxic medicine. When handling or preparing the medicine, you should exercise caution to minimize exposure.

Since Bortezomib medac does not contain preservatives, strict aseptic techniques must be followed during handling and preparation.

1.1

Preparation of the 1 mg vial: carefully add 1 mlof sterile, 9 mg/ml (0.9%) sodium chloride injection to the vial containing the Bortezomib medac powder, using a 1 ml syringe, without removing the vial stopper.

The dissolution of the lyophilized powder takes less than 2 minutes.

The resulting solution will have a concentration of 1 mg/ml.

After reconstitution, the solution is 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.

Discard the solution if particulate matter or discoloration is observed.

Check the vial label to ensure that the correct dose is administered intravenously(1 mg/ml).

1.3

The reconstituted solution contains no preservatives and should be used immediately.

However, the chemical and physical stability of the reconstituted solution has been demonstrated for 8 days when stored at 25°C and 60% relative humidity or 15 days when stored at 5 ± 3°C in the dark, both in the vial and in a polypropylene syringe.

The total storage time of the reconstituted solution should not exceed 24 hours at 2-8°C, unless the preparation and dilution have been carried out under controlled and validated aseptic conditions.

2. Administration

• Withdraw the appropriate dose of the reconstituted solution based on the patient's body surface area.
• Confirm the dose and concentration of the medicine in the syringe (ensure that the syringe is labeled as for intravenous use).
• Administer the solution as an intravenous bolus injection over 3 to 5 seconds through a central or peripheral intravenous catheter.
• Flush the intravenous catheter with a small amount of sterile, 9 mg/ml (0.9%) sodium chloride injection after administration of Bortezomib medac.

Bortezomib medac 1 mg powder for solution for injection is for INTRAVENOUS USE ONLY. Do not administer by any other route. Intrathecal administration has resulted in death.

3. Disposal

The vial is for single use only.

Dispose of any unused solution or waste material in accordance with local requirements.