Bortezomib Kern Pharma 3.5 mg powder for solution for injection EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Bortezomib Kern Pharma 3.5 mg powder for solution for injection EFG

Read the entire leaflet carefully before you start taking 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 it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Bortezomib Kern Pharma is and what it is used for

Bortezomib Kern Pharma 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 functioning.

Bortezomib Kern Pharma is used to treat 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 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 considered suitable candidates for high-dose chemotherapy followed by stem cell transplantation;
• in combination with dexamethasone or dexamethasone plus thalidomide, for patients whose disease has not been previously treated and who are undergoing high-dose chemotherapy prior to stem cell transplantation (induction treatment).

Bortezomib Kern Pharma is also used to treat 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 who are not considered suitable candidates for stem cell transplantation.

2. What you need to know before using Bortezomib Kern Pharma

Do not take Bortezomib Kern Pharma:

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting bortezomib if you have:

• low red or white blood cell counts
• bleeding problems and/or low platelet count in the blood
• diarrhea, constipation, nausea, or vomiting
• a history of fainting, dizziness, or lightheadedness
• kidney problems
• moderate to severe liver problems
• a history of numbness, tingling, or pain in the hands or feet (neuropathy)
• heart problems or blood pressure issues
• difficulty breathing or cough
• seizures
• shingles (localized, including around the eyes, or widespread throughout the body)
• symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss or changes, and difficulty breathing
• memory loss, changes in thinking, difficulty walking, or vision loss. These may be signs of a serious brain infection, and your doctor may recommend further testing and monitoring.

You will need to have regular blood tests before and during treatment with Bortezomib Kern Pharma to monitor your blood cell counts regularly.

You must inform your doctor if you have mantle cell lymphoma and are receiving rituximab in combination with Bortezomib Kern Pharma:

• if you currently have or have previously had hepatitis infection. In a few cases, patients who have had hepatitis B may experience reactivation of the infection, which can be fatal. If you have a history of hepatitis B infection, your doctor will closely monitor you for signs of active hepatitis.

Before starting treatment with Bortezomib Kern Pharma, you should read the package leaflets of all the medicines you are taking in combination with Bortezomib Kern Pharma to review information related to these medicines. When thalidomide is used, special attention must be paid to pregnancy testing and preventive measures (see Pregnancy and Breastfeeding in this section).

Children and adolescents

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

Other medicines and Bortezomib Kern Pharma

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including medicines obtained without a prescription.

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 breastfeeding

You must not use Bortezomib Kern Pharma if you are pregnant unless clearly necessary.

Women of childbearing potential must use effective contraception during treatment and for 8 months after stopping treatment. Talk to your doctor if you wish to freeze eggs before starting treatment. Men must not father a child while using Bortezomib Kern Pharma and must use effective contraception during treatment and for 5 months after stopping treatment. Talk to your doctor if you wish to preserve your sperm before starting treatment.

You must not breastfeed while using Bortezomib Kern Pharma. Consult your doctor about when it is safe to restart breastfeeding after completing your treatment.

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

Driving and using machines

Bortezomib Kern Pharma 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 exercise caution.

3. How to take Bortezomib Kern Pharma

Your doctor will determine the dose of Bortezomib Kern Pharma based on your height and weight (body surface area). The usual starting dose of Bortezomib Kern Pharma is 1.3 mg/m² body surface area, administered twice weekly. 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 Kern Pharma is given alone, you will receive 4 doses of Bortezomib Kern Pharma 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) constitutes one treatment cycle. You may receive up to 8 cycles (24 weeks).

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

When Bortezomib Kern Pharma is administered with pegylated liposomal doxorubicin, you will receive Bortezomib Kern Pharma intravenously or subcutaneously in a 21-day treatment cycle, and pegylated liposomal doxorubicin 30 mg/m² is administered intravenously on day 4 of the 21-day Bortezomib Kern Pharma treatment cycle, via infusion after the Bortezomib Kern Pharma injection.

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

When Bortezomib Kern Pharma is administered with dexamethasone, you will receive Bortezomib Kern Pharma 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 Kern Pharma treatment cycle.

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

Previously untreated multiple myeloma

If you have not previously been treated for multiple myeloma and are not a candidate for receiving a stem cell transplant, you will receive Bortezomib Kern Pharma intravenously or subcutaneously 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 Kern Pharma is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, Bortezomib Kern Pharma is administered once weekly 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 a candidate for a stem cell transplant, you will receive Bortezomib Kern Pharma intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction therapy.

When Bortezomib Kern Pharma is administered with dexamethasone, you will receive Bortezomib Kern Pharma 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 Kern Pharma treatment cycle. You will receive 4 cycles (12 weeks).

When Bortezomib Kern Pharma is administered with thalidomide and dexamethasone, the duration of a 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 Kern Pharma 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, it 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 previously been treated for mantle cell lymphoma, you will receive Bortezomib Kern Pharma intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

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

The following medications are administered via intravenous infusion on day 1 of the 21-day Bortezomib Kern Pharma 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 Kern Pharma treatment cycle.

How Bortezomib Kern Pharma is administered

This medicine is administered intravenously or subcutaneously. Bortezomib Kern Pharma will be given to you by a healthcare professional experienced in the use of cytotoxic medicines.

The Bortezomib Kern Pharma powder must be reconstituted before administration. This will be done by a healthcare professional. The reconstituted solution is then injected into a vein or under the skin. The intravenous injection is rapid and lasts between 3 and 5 seconds. The subcutaneous injection is administered in the thighs or abdomen.

If you receive more Bortezomib Kern Pharma 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 that an overdose occurs, 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 will experience them. Some of these effects may be serious.

If you are administered Bortezomib Kern Pharma 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 Kern Pharma 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 Kern Pharma 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 (contusions) or bleeding without evident injury (for example, bleeding in the intestine, stomach, mouth and gums, 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 Kern Pharma for the treatment of multiple myeloma, the adverse effects you may experience are listed below:

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

• Tenderness, 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
• Feeling unwell (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 fluids than usual. Your doctor may give you another medicine to control the diarrhea
• Exhaustion (tiredness), 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 feeling of discomfort, 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
• Itchy skin, skin lumps, or dry skin
• Facial flushing or rupture of small capillaries
• Redness of the skin
• Dehydration
• Stomach burning, bloating, burping, flatulence, stomach pain, intestinal or stomach bleeding
• Impaired liver function
• 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, increase or decrease in heart rate
• Kidney failure
• Inflammation of a vein, blood clots in veins and lungs
• Blood clotting disorders
• Inadequate circulation
• Inflammation of the lining of the heart 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, alterations or changes in, or decreased sensitivity (touch, hearing, taste, smell), attention disorders, tremors, jerking movements
• Arthritis, including inflammation of the joints of the fingers, toes, and jaw
• Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exertion, breathing that may become shallow, difficult, or stop, gasping breaths
• Hiccups, speech disorders
• Increase or decrease in urine production (due to kidney injury), pain when urinating or blood/proteins in urine, fluid retention
• Altered level of consciousness, confusion, altered or lost memory
• Hypersensitivity
• Hearing loss, deafness, or ringing in the ears (tinnitus), 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 watery eyes, eye pain, dry eyes, eye infections, eyelid cyst (chalazion), red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye bleeding
• Swelling of lymph nodes
• Stiffness of joints or muscles, 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, mouth ulcers, 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
• Inflammation of the pancreas, obstruction of bile ducts
• Genital pain, difficulty achieving an erection
• Weight gain
• Thirst
• Hepatitis
• Injection site reactions or device-related disorders
• Skin reactions and skin 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 patches 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
• 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
• Brain 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 skin itching or skin lumps, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
• Breast disorders
• Vaginal laceration
• 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 swelling, liver bleeding
• Kidney cancer
• Skin disease resembling psoriasis
• Skin cancer
• Paleness of the skin
• Increase in platelets or plasma cells (a type of white blood cell) in the blood
• Blood clot in small blood vessels (thrombotic microangiopathy)
• Abnormal reaction to blood transfusions
• Partial or complete loss of vision
• 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
• Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)
• Multi-organ failure
• Death

If you are administered Bortezomib Kern Pharma together with other medicines for the treatment of mantle cell lymphoma, the adverse effects you may experience are listed below:

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

• Pneumonia
• Loss of appetite
• Tenderness, 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 zoster (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, increase or decrease in 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
• Impaired liver function
• Itchy 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 discomfort
• 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 skin 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, shortness of breath without exertion, breathing that may become shallow, difficult, or stop, gasping breaths
• Blood clots in the lungs
• Yellowing of the eyes and skin (jaundice)
• Eyelid cyst (chalazion), red and swollen eyelids

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

• Blood clot 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 it is a possible adverse effect not listed in this leaflet. You can also report them directly via 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 Kern Pharma

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 outer packaging following "EXP". The expiry date refers to the last day of the month indicated.

Store the vial in its original packaging to protect it from light.

This medicine does not require any special storage temperature conditions.

Reconstituted solution

Chemical and physical stability of the reconstituted solution has been demonstrated for a period of 8 days at 25°C/60% RH and 15 days at 2–8°C RH when stored in the dark, in either the original vial and/or a polypropylene syringe.

From a microbiological standpoint, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user.

Bortezomib Kern Pharma is intended for single use only.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines and packaging you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Bortezomib Kern Pharma

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as manitol boronic ester).
• The other component is mannitol (E421).

Intravenous reconstitution:

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

Subcutaneous reconstitution:

After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

Appearance of the product and contents of the container

Bortezomib Kern Pharma powder for injectable solution is a white to off-white paste or powder.

Each pack of Bortezomib Kern Pharma 3.5 mg powder for injectable solution contains 1 glass vial with a rubber stopper and a blue flip-off cap.

Each pack contains 1 single-use vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Kern Pharma, S.L.

Venus, 72 – Pol. Ind. Colón II

08228 Terrassa – Barcelona

Spain

Manufacturer:

Synthon Hispania, S.L.

C/ Castelló no1, Pol. Las Salinas

08830 Sant Boi de Llobregat (Barcelona)

Spain

or

Synthon s.r.o.

Brnenská 32/cp. 597,

678 01 Blansko

Czech Republic

This medicinal product is authorized in the European Economic Area member states under the following names:

Netherlands	Bortezomib Synthon 3.5 mg, powder for solution for injection
France	Bortezomib Synthon 3.5 mg powder for injectable solution
Spain	Bortezomib Kern Pharma 3.5 mg powder for injectable solution EFG

Date of the latest review of this leaflet: April 2025

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

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

SINCE BORTEZOMIB KERN PHARMA DOES NOT CONTAIN PRESERVATIVES, STRICT ASEPTIC TECHNIQUE SHOULD BE FOLLOWED DURING HANDLING.

1.1 Preparation of a 3.5 mg vial: carefully add 3.5 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing the Bortezomib Kern Pharma lyophilized powder, using a suitably sized syringe without removing the vial stopper. Dissolution of the lyophilized powder is complete within less than 2 minutes.

The resulting solution concentration will be 1 mg/ml. The solution should be clear and colourless, with a final pH of 4 to 7. It is not necessary to verify 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 reconstituted solution contains no preservatives and should be used immediately after preparation. However, chemical and physical in-use stability has been demonstrated for 8 days at 25°C/60%RH and 15 days at 2–8°C when stored in the dark in the original vial and/or syringe.

From a microbiological standpoint, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate amount of the reconstituted 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).
• Administer the solution as an intravenous bolus over 3–5 seconds through a peripheral or central intravenous catheter into a vein.
• Flush the peripheral or central catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

BORTEZOMIB KERN PHARMA 3.5 mg powder for solution for injection MUST BE ADMINISTERED ONLY BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has resulted in fatal cases.

3. ELIMINATION

A vial is for single use only, and 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 agents.

The following information is intended for healthcare professionals only:

Only the 3.5 mg vial may be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

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

SINCE BORTEZOMIB KERN PHARMA DOES NOT CONTAIN PRESERVATIVES, STRICT ASEPTIC TECHNIQUE SHOULD BE FOLLOWED DURING HANDLING.

1.1 Preparation of a 3.5 mg vial: carefully add 1.4 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing the Bortezomib Kern Pharma lyophilized powder, using a suitably sized syringe without removing the vial stopper. Dissolution of the lyophilized powder is complete within less than 2 minutes.

The resulting solution concentration will be 2.5 mg/ml. The solution should be clear and colourless, with a final pH of 4 to 7. It is not necessary to verify 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 reconstituted solution contains no preservatives and should be used immediately after preparation. However, chemical and physical in-use stability has been demonstrated for 8 days at 25°C/60%RH and 15 days at 2–8°C when stored in the dark in the original vial and/or syringe.

From a microbiological standpoint, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate amount of the reconstituted 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 reconstituted 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 Kern Pharma, either a less concentrated subcutaneous solution of Bortezomib Kern Pharma (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

BORTEZOMIB KERN PHARMA 3.5 mg powder for solution for injection MUST BE ADMINISTERED ONLY BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has resulted in fatal cases.

3. ELIMINATION

A vial is for single use only, and 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 agents.