Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bortezomib STADA 2.5 mg/ml solution for injection

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

Keep this leaflet, as you may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

What Bortezomib STADA is and what it is used for
What you need to know before using Bortezomib STADA
How to use Bortezomib STADA
Possible side effects
How to store Bortezomib STADA
Contents of the pack and other information

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

Bortezomib STADA contains the active substance bortezomib, a "proteasome inhibitor". Proteasomes play an important role in regulating cell function and growth. Bortezomib can destroy cancer cells by interfering with their normal function.

Bortezomib is used in the treatment of multiple myeloma (a cancer of the bone marrow) in patients over 18 years of age:

alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (progressing) after having received at least one prior treatment, and for those patients for whom stem cell transplantation has not worked or is not suitable
in combination with melphalan and prednisone, for patients whose disease has not been previously treated and who are not suitable candidates for high-dose chemotherapy prior to stem cell transplantation
in combination with dexamethasone or dexamethasone plus thalidomide, for patients whose disease has not been previously treated and who are receiving high-dose chemotherapy prior to stem cell transplantation (induction treatment)

Bortezomib is also used in the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged 18 years or older, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, for patients whose disease has not been previously treated and for whom stem cell transplantation is not considered appropriate.

2. What you need to know before starting to use Bortezomib STADA

DO NOT use Bortezomib STADA

if you are allergic to bortezomib, boron, or any of the other ingredients of this medicine (listed in section 6)
if you have certain severe lung or heart problems

Warnings and precautions

Tell your doctor, pharmacist, or nurse before using bortezomib, especially if you have any of the following:

? low red blood cell or white blood cell count

? bleeding problems and/or low platelet count in the blood

? diarrhoea, constipation, nausea, or vomiting

? history of fainting, dizziness, or lightheadedness

? kidney problems

? moderate to severe liver problems

? numbness, tingling, or pain in hands or feet (neuropathy) in the past

? heart problems or blood pressure issues

? difficulty breathing or cough

? seizures

? shingles (localized including around the eyes or widespread throughout the body)

? symptoms of tumour lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss or changes, and difficulty breathing

? memory loss, thinking changes, difficulty walking, or vision loss

These may be signs of a serious 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 to monitor your blood cell counts regularly.

Inform your doctor if you have mantle cell lymphoma and are receiving rituximab together with bortezomib:

? if you think you currently have or have previously had hepatitis infection. In some cases, patients who have had hepatitis B may experience recurrent hepatitis episodes, which can be fatal. If you have a history of hepatitis B infection, your doctor will closely monitor you for signs of active hepatitis B.

Before starting treatment with bortezomib, you should read the package leaflets of all the medicines you are to take in combination with bortezomib to review information related to these medicines.

When using thalidomide, special attention must be paid to pregnancy testing and preventive measures (see Pregnancy and Breast-feeding in this section).

Children and adolescents

Bortezomib must not be used in children and adolescents because it is not known how the medicine will affect them.

Using Bortezomib STADA with other medicines

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines.

In particular, inform your doctor if you are 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 for depression or other conditions
oral antidiabetic medicines

Pregnancy and breast-feeding

Do not use bortezomib if you are pregnant unless clearly necessary.

Women of childbearing potential must use effective contraception during treatment and for 8 months after treatment ends. Talk to your doctor about freezing eggs before starting treatment.

Men must not father a child while using bortezomib and must use effective contraception during treatment and for 5 months after treatment ends. Talk to your doctor about preserving sperm before starting treatment.

You must not breast-feed while using bortezomib. Consult your doctor about when it is safe to resume breast-feeding after completing your treatment.

Thalidomide causes birth defects and fetal death. When bortezomib is administered in combination with thalidomide, the thalidomide pregnancy prevention programme must be followed (refer to the thalidomide package leaflet).

Driving and using machines

Bortezomib may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate tools or machinery if you experience these side effects; even if you do not experience them, you should still be cautious.

Bortezomib STADA contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial; this is essentially “sodium-free”.

3. How to use Bortezomib STADA

Your doctor will determine the dose of bortezomib based on your height and weight (body surface area). The usual starting dose of bortezomib is 1.3 mg/m² of body surface area, administered twice a week. Your doctor may adjust the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain adverse effects, and your underlying condition (e.g., liver problems).

Relapsed multiple myeloma

When bortezomib is given alone, you will receive 4 doses of bortezomib intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day period (3 weeks) corresponds to one treatment cycle. You may receive up to 8 cycles (24 weeks).

It is also possible that you will receive bortezomib in combination with pegylated liposomal doxorubicin or dexamethasone.

When bortezomib is administered together with pegylated liposomal doxorubicin, you will receive bortezomib intravenously or subcutaneously in a 21-day treatment cycle, and pegylated liposomal doxorubicin 30 mg/m² is administered on day 4 of the 21-day bortezomib treatment cycle, by intravenous infusion after the bortezomib injection. You may receive up to 8 cycles (24 weeks).

When bortezomib is administered together with dexamethasone, you will receive bortezomib intravenously or subcutaneously in a 21-day treatment cycle, and dexamethasone 20 mg is administered orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day bortezomib treatment cycle. You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been previously treated for multiple myeloma and are not eligible for hematopoietic stem cell transplantation, you will receive bortezomib in combination with two other medicines: melphalan and prednisone.

In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

? In cycles 1 to 4, bortezomib is administered twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.

? In cycles 5 to 9, bortezomib is administered once a week on days 1, 8, 22, and 29.

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 you have not previously received treatment for multiple myeloma and are eligible for hematopoietic stem cell transplantation, you will receive bortezomib intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction therapy.

When bortezomib is administered together with dexamethasone, you will receive bortezomib intravenously or subcutaneously in a 21-day treatment cycle, and dexamethasone is administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day bortezomib treatment cycle. You will receive 4 cycles (12 weeks).

When bortezomib is administered together with thalidomide and dexamethasone, the duration of one treatment cycle is 28 days (4 weeks).

Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day bortezomib treatment cycle, and thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the thalidomide dose is increased to 100 mg on days 15–28, and from the second cycle onwards may be further increased to 200 mg daily. You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not been previously treated for mantle cell lymphoma, you will receive bortezomib intravenously or subcutaneously in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without treatment. The duration of one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines are administered by intravenous infusion on day 1 of the 21-day bortezomib 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 treatment cycle.

How Bortezomib STADA is administered

This medicine is administered subcutaneously and, after reconstitution, also intravenously. Bortezomib will be administered by a healthcare professional experienced in the use of cytotoxic medicines.

The solution is then injected either into a vein or under the skin. The intravenous injection is rapid, lasting between 3 and 5 seconds. The subcutaneous injection is administered in the thighs or abdomen.

If you receive more Bortezomib STADA than you should

This medicine will be administered by your doctor or nurse, so it is unlikely that you will receive too much. In the unlikely event of an overdose, your doctor will monitor you for any adverse effects.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. Some of these effects may be serious.

If you are administered bortezomib for multiple myeloma or mantle cell lymphoma, inform your doctor immediately if you notice any of the following symptoms:

Muscle cramps, muscle weakness
Confusion, loss or changes in vision, blindness, seizures, headaches
Difficulty breathing, swelling of the feet, or changes in heart rhythm, high blood pressure, fatigue, fainting
Cough and difficulty breathing or chest tightness.

Treatment with bortezomib may very commonly cause a decrease in the number of red blood cells, white blood cells, and platelets in the blood. Therefore, you will need to have regular blood tests before and during treatment with bortezomib to monitor your blood cell counts regularly. You may experience a reduction in the number of:

Platelets, which may make you more prone to bruising (bruises) or bleeding without evident injury (for example, intestinal, stomach, mouth, and gum bleeding, or bleeding in the brain or liver)
Red blood cells, which may cause anemia, with symptoms such as fatigue and paleness
White blood cells, which may make you more susceptible to infections or flu-like symptoms.

If you are administered bortezomib for the treatment of multiple myeloma, the adverse effects you may experience include the following:

Very common adverse effects (may affect more than 1 in 10 patients)

? Sensitivity, numbness, tingling, or burning sensation in the skin or pain in hands or feet due to nerve damage
? Reduction in the number of red blood cells and/or white blood cells (see above)
? Fever
? Nausea or vomiting, loss of appetite
? Constipation with or without bloating (may be severe)
? Diarrhea: if it occurs, it is important that you drink more water than usual. Your doctor may give you another medicine to control the diarrhea
? Exhaustion (fatigue), feeling of weakness
? Muscle pain, bone pain

Common adverse effects (may affect up to 1 in 10 patients)

? Low blood pressure, sudden drop in blood pressure when standing, which could lead to fainting
? High blood pressure
? Decreased kidney function
? Headache
? General malaise, pain, dizziness, lightheadedness, feeling of weakness or loss of consciousness
? Chills
? Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness
? Herpes zoster (localized, including around the eyes or spread throughout the body)
? Chest pain or difficulty breathing during exercise
? Various types of rashes
? Itching, skin lumps, or dry skin
? Facial flushing or rupture of small capillaries
? Redness of the skin
? Dehydration
? Stomach burning, bloating, belching, flatulence, stomach pain, intestinal or stomach bleeding
? Liver function abnormalities
? Mouth or lip sores, dry mouth, mouth ulcers, or sore throat
? Weight loss, loss of taste
? Muscle cramps, muscle spasms, muscle weakness, limb pain
? Blurred vision
? Infection of the outer layer of the eye and inner surface of the eyelids (conjunctivitis)
? Nosebleeds
? Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation
? Swelling of the body, including around the eyes and other body parts

Uncommon adverse effects (may affect up to 1 in 100 patients)

? Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
? Kidney failure
? Vein inflammation, blood clots in veins and lungs
? Blood clotting problems
? Poor circulation
? Inflammation of the heart lining or fluid around the heart
? Infections, including urinary tract infections, flu, herpes virus infection, ear infection, and cellulitis
? Bloody stools or bleeding from mucous membranes, for example, from the mouth or vagina
? Cerebrovascular disorders
? Paralysis, seizures, falls, movement disorders, changes or disturbances in, or decreased sensitivity (touch, hearing, taste, smell), attention disorders, tremors, jerking
? Arthritis, including inflammation of the joints of the fingers and toes and jaw
? Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, breathlessness without exercise, breathing that may become shallow, difficult, or stop, wheezing
? Hiccups, speech disorders
? Increased or decreased urine production (due to kidney injury), pain when urinating, or blood/proteins in the urine, fluid retention
? Altered level of consciousness, confusion, altered or loss of memory
? Hypersensitivity
? Hearing loss, deafness, or ringing in the ears, ear discomfort
? Hormonal disorders that may affect salt and water absorption
? Overactivity of the thyroid gland
? Inability to produce sufficient insulin or resistance to normal insulin levels
? Eye irritation or inflammation, excessively wet eyes, eye pain, dry eyes, eye infections, eyelid lump (chalazion), red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye hemorrhage
? Swelling of lymph nodes
? Joint or muscle stiffness, feeling of heaviness, groin pain
? Hair loss and abnormal hair texture
? Allergic reactions
? Redness or pain at the injection site
? Mouth pain
? Infections or inflammation of the mouth, ulcers in the mouth, esophagus, stomach, and intestine, sometimes associated with pain or bleeding, reduced intestinal movement (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood
? Skin infections
? Bacterial and viral infections
? Dental infection
? Pancreatitis, obstruction of bile ducts
? Genital pain, difficulty achieving an erection
? Weight gain
? Thirst
? Hepatitis
? Injection site disorders or those related to the injection device

Skin reactions and disorders (which may be severe and life-threatening), skin ulcers
? Bruising, falls, and injuries
? Inflammation or bleeding of blood vessels appearing as small red or purple spots (usually on the legs) up to large bruise-like areas under the skin or tissue
? Benign cysts
? A serious and reversible brain disorder including seizures, high blood pressure, headaches, fatigue, confusion, blindness, or other vision problems.

Rare adverse effects (may affect up to 1 in 1,000 patients)

? Heart problems, including heart attack, angina
? Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)

Flushing
? Discoloration of veins
? Inflammation of spinal nerves
? Ear problems, ear bleeding
? Underactivity of the thyroid gland
? Budd–Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins)
? Changes or abnormalities in intestinal function
? Cerebral hemorrhage
? Yellowing of the eyes and skin (jaundice)
? Severe allergic reaction (anaphylactic shock), whose signs may include difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense itching or skin lumps, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
? Breast disorders
? Vaginal tear
? Genital inflammation
? Inability to tolerate alcohol consumption
? Wasting or loss of body mass
? Increased appetite
? Fistula
? Joint effusion
? Cysts in the joint lining (synovial cysts)
? Fracture
? Breakdown of muscle fibers causing other complications
? Liver enlargement, liver hemorrhage
? Kidney cancer
? Skin disease resembling psoriasis
? Skin cancer
? Skin pallor
? Increase in platelets or plasma cells (a type of white blood cell) in the blood
Blood clots in small blood vessels (thrombotic microangiopathy)
? Abnormal reaction to blood transfusions
? Partial or complete vision loss
? Loss of libido
? Drooling
? Protruding eyes
? Light sensitivity
? Rapid breathing
? Rectal pain
? Gallstones
? Hernia
? Wounds
? Weak or brittle nails
? Abnormal protein deposits in vital organs
? Coma
? Intestinal ulcers
? Multi-organ failure
? Death

If you are administered bortezomib in combination with other medicines for the treatment of mantle cell lymphoma, the adverse effects you may experience include the following:

Very common adverse effects (may affect more than 1 in 10 patients)

? Pneumonia
? Loss of appetite
? Sensitivity, numbness, tingling, or burning sensation in the skin or 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 texture
? Exhaustion, feeling of weakness
? Fever

Common adverse effects (may affect up to 1 in 10 patients)

? Herpes (localized, including around the eyes or spread throughout the body)
? Herpes virus infection
? Bacterial and viral infections
? Respiratory infections, bronchitis, cough with phlegm, flu-like illness
? Fungal infections
? Hypersensitivity (allergic reaction)
? Inability to produce sufficient insulin or resistance to normal insulin levels
? Fluid retention
? Difficulty or problems sleeping
? Loss of consciousness
? Altered level of consciousness, confusion
? Dizziness
? Increased heart rate, high blood pressure, sweating
? Abnormal vision, blurred vision
? Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
? High or low blood pressure
? Sudden drop in blood pressure when standing, which could lead to fainting
? Difficulty breathing during exercise
? Cough
? Hiccups
? Ringing in the ears, ear discomfort
? Intestinal or stomach bleeding
? Stomach burning
? Stomach pain, bloating
? Difficulty swallowing
? Infection or inflammation of stomach and intestine
? Stomach pain
? Mouth or lip sores, sore throat
? Liver function abnormalities
? Itching of the skin
? Redness of the skin
? Rash
? Muscle spasms
? Urinary tract infection
? Limb pain
? Swelling of the body, including around the eyes and other body parts
? Chills
? Redness and pain at the injection site
? General feeling of malaise
? Weight loss
? Weight gain

Uncommon adverse effects (may affect up to 1 in 100 patients)

? Hepatitis
? Severe allergic reaction (anaphylactic reaction), whose signs may include difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense itching or skin lumps, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
? Movement disorders, paralysis, jerking
? Dizziness
? Hearing loss, deafness
? Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, breathlessness without exercise, breathing that may become shallow, difficult, or stop, wheezing
? Blood clots in the lungs
? Yellowing of the eyes and skin (jaundice)

Eyelid lump (chalazion), red and swollen eyelids

Rare adverse effects (may affect up to 1 in 1,000 patients)

Blood clots in small blood vessels (thrombotic microangiopathy)
Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bortezomib STADA

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

Do not use this medicine after the expiry date stated on the vial and packaging following EXP.

Store the unopened vial in the refrigerator (between 2 °C and 8 °C). Keep the vial in the outer packaging to protect it from light.

The diluted solution should be used immediately after preparation. If the diluted solution is not used immediately, the storage times and conditions prior to use are the responsibility of the user. However, the diluted solution is chemically and physically stable for 28 days when stored between 2 °C and 8 °C protected from light, for 7 days when stored at 25 °C protected from light, or for 24 hours when stored at 25 °C (under normal indoor lighting conditions) in the original vial and/or a polypropylene syringe.

Regarding stability in the vial and/or syringe, the same storage times apply to both diluted and undiluted solutions.

Bortezomib is for single use only. Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations.

6. Contents of the pack and other information

Composition of Bortezomib STADA

The active substance is bortezomib.

Each vial contains 1.4 ml of injectable solution containing 3.5 mg of bortezomib (as boric ester of mannitol).
Each vial contains 2.8 ml of injectable solution containing 7 mg of bortezomib (as boric ester of mannitol).

The other components are mannitol, sodium chloride, and water for injectable preparations.

Intravenous route:

After dilution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.

Subcutaneous route:

1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

Appearance of the product and contents of the container

Bortezomib STADA injectable solution is a clear, colourless to pale yellow solution.

Vial containing 1.4 ml of injectable solution / 3.5 mg of bortezomib

Each pack of Bortezomib STADA 2.5 mg/ml solution for injection contains 1 glass vial of 10 ml with a yellow flip-off cap made of polypropylene.

Vial containing 2.8 ml of injectable solution / 7 mg of bortezomib

Each pack of Bortezomib STADA 2.5 mg/ml solution for injection contains 1 glass vial of 10 ml with a dark blue flip-off cap made of polypropylene.

[Each vial is packaged in a transparent polycarbonate (PC) container with a reclosable polypropylene (PP) flip-off cap tamper-evident lid.]

Marketing Authorisation Holder

Laboratorio STADA, S.L.
C/Frederic Mompou, 5
08960 Sant Just Desvern (Barcelona)
Spain
[email protected]

Manufacturer

STADA Arzneimittel AG
Stadastrasse 2 – 18
61118 Bad Vilbel
Germany

Date of the most recent revision of this leaflet: August 2025

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

The following information is intended for healthcare professionals only:

1. PREPARATION FOR INTRAVENOUS INJECTION

Pregnant individuals must not handle this medicine.

Note: Bortezomib is a cytotoxic agent. Therefore, caution must be taken during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

SINCE BORTEZOMIB STADA DOES NOT CONTAIN PRESERVATIVES, STRICTLY ASEPTIC TECHNIQUE SHOULD BE FOLLOWED DURING HANDLING.

Vial containing 1.4 ml of injectable solution / 3.5 mg of bortezomib

1.1. Preparation of a 3.5 mg vial: add 2.1 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib STADA.

The resulting solution concentration will be 1 mg/ml. The solution should be clear, colourless to pale yellow, with a final pH of 4 to 7. There is no need to check the pH of the solution.

Vial containing 2.8 ml of injectable solution / 7 mg of bortezomib

1.1. Preparation of a 7 mg vial: add 4.2 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib STADA.

The resulting solution concentration will be 1 mg/ml. The solution should be clear, colourless to pale yellow, with a final pH of 4 to 7. There is no need to check the pH of the solution.

1.2. Before administration, visually inspect the solution for the presence of particles and discoloration. If discoloration or particles are observed, the solution must be discarded. Confirm that the correct dose for intravenous administration (1 mg/ml) is being used.

1.3. The diluted solution contains no preservatives and should be used immediately after preparation. If the diluted solution is not used immediately, storage times and conditions prior to use are the user's responsibility. However, chemical and physical stability during use of the diluted solution has been demonstrated for up to 28 days when stored between 2°C and 8°C protected from light, 7 days when stored at 25°C protected from light, or 24 hours when stored at 25°C (under normal indoor lighting conditions) in the original vial and/or polypropylene syringe.

During preparation for administration and during administration, it is not necessary to protect the product from light.

2. ADMINISTRATION

? After dilution, withdraw the appropriate amount of diluted solution according to the dose calculated based on the patient's Body Surface Area.

? Confirm the dose and concentration in the syringe before use (ensure the syringe is labelled for intravenous administration).

? Inject the solution as an intravenous bolus over 3-5 seconds through a peripheral or central intravenous catheter into a vein.

? Flush the peripheral or intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

Bortezomib STADA 2.5 mg/ml solution for injection IS FOR INTRAVENOUS OR SUBCUTANEOUS USE ONLY. Do not administer by other routes. Intrathecal administration has resulted in fatal cases.

3. DISPOSAL

Each vial is for single use only; any remaining solution must be discarded.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations for cytotoxic medicines.

The following information is intended for healthcare professionals only:

1. PREPARATION FOR SUBCUTANEOUS INJECTION

Pregnant individuals must not handle this medicine.

Note: Bortezomib is a cytotoxic agent. Therefore, caution must be taken during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

SINCE BORTEZOMIB STADA DOES NOT CONTAIN PRESERVATIVES, STRICTLY ASEPTIC TECHNIQUE SHOULD BE FOLLOWED DURING HANDLING.

1.1 Bortezomib STADA is ready for use.

The resulting solution concentration will be 2.5 mg/ml. The solution is clear and colourless, with a pH of 4.0 to 6.0. There is no need to check the pH of the solution.

1.2 Before administration, visually inspect the solution for the presence of particles and discoloration. If discoloration or particles are observed, the solution must be discarded. Confirm that the correct dose for subcutaneous administration (2.5 mg/ml) is being used.

1.3 The medicine contains no preservatives and should be used immediately after withdrawing the appropriate amount of solution. If the solution is not used immediately, storage times and conditions prior to use are the user's responsibility. However, chemical and physical stability during use has been demonstrated for up to 28 days when stored between 2°C and 8°C protected from light, 7 days when stored at 25°C protected from light, or 24 hours when stored at 25°C (under normal indoor lighting conditions) in the original vial and/or polypropylene syringe.

During preparation for administration and during administration, it is not necessary to protect the product from light.

2. ADMINISTRATION

? Withdraw the appropriate amount of solution according to the dose calculated based on the patient's Body Surface Area.

? Confirm the dose and concentration in the syringe before use (ensure the syringe is labelled for subcutaneous administration).

? Inject the solution subcutaneously at an angle of 45–90°.

? The solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left side).

? Injection sites should be rotated with each administration.

? If local reactions occur at the injection site following subcutaneous administration of Bortezomib STADA, either a less concentrated subcutaneous solution of Bortezomib STADA (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.