Bortezomib Sandoz BV

Package leaflet: Information for the user

Bortezomib Sandoz BV 3.5 mg powder for solution for injection

Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Bortezomib Sandoz BV is and what it is used for

Bortezomib Sandoz BV contains the active substance bortezomib, a so-called "proteasome inhibitor".
Proteasomes play an important role in regulating cell functions and cell growth.
By interfering with their function, bortezomib can kill tumor cells.
Bortezomib Sandoz BV is used in the treatment of multiple myeloma (a type of malignant neoplasm
of the bone marrow) in patients aged over 18 years:

• alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients with progressive disease after having received at least one prior therapy and for whom blood stem cell transplantation has been unsuccessful or is not feasible.
• in combination with melphalan and prednisone, for previously untreated patients who cannot receive high-dose chemotherapy with blood stem cell transplantation.
• in combination with dexamethasone or dexamethasone together with thalidomide, for previously untreated patients prior to receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment).

Bortezomib Sandoz BV is used for the treatment of mantle cell lymphoma (a type of malignant
neoplasm affecting the lymph nodes) in patients aged 18 years or older, in combination with the medicines
rituximab, cyclophosphamide, doxorubicin, and prednisone, for previously untreated patients for whom blood stem cell transplantation is not feasible.

2. What you need to know before using Bortezomib Sandoz BV

Do not use Bortezomib Sandoz BV

• 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 problems.

Warnings and precautions
Talk to your doctor or pharmacist before using Bortezomib Sandoz BV if you have:

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

You will need to have regular blood tests before and during treatment with Bortezomib Sandoz BV to monitor your blood cell counts continuously.
If you have mantle cell lymphoma and are being treated with rituximab in combination with Bortezomib Sandoz BV, inform your doctor:

• if you think you have hepatitis or have had it in the past. In some cases, patients who have had hepatitis B may experience a reactivation of the disease, which can be fatal. If you have previously had hepatitis B infection, your doctor will need to monitor you closely for signs and symptoms of active hepatitis B.

Read the package leaflets of all other medicines you are taking in combination with Bortezomib Sandoz BV for information about these medicines before starting treatment with Bortezomib Sandoz BV.
When taking thalidomide, special attention must be paid to the instructions regarding pregnancy testing and the pregnancy prevention programme (see "Pregnancy and breastfeeding" in this section).

Children and adolescents
Bortezomib Sandoz BV must not be used in children and adolescents, as the effect of this medicine in this population group is unknown.

Other medicines and Bortezomib Sandoz BV
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those 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 to treat depression or other conditions
• oral antidiabetic medicines

Pregnancy and breastfeeding
You must not use Bortezomib Sandoz BV during pregnancy unless strictly necessary.
Men and women receiving treatment with Bortezomib Sandoz BV must use effective contraceptive methods during treatment and for up to 3 months after treatment ends. If pregnancy occurs despite these precautions, inform your doctor immediately.
You must not breastfeed during treatment with Bortezomib Sandoz BV. Discuss with your doctor when it is appropriate to resume breastfeeding after treatment ends.
Thalidomide causes birth defects and fetal death. When Bortezomib Sandoz BV is administered together with thalidomide, you must follow thalidomide's pregnancy prevention programme (see the package leaflet for thalidomide).

Driving and using machines
Bortezomib Sandoz BV may cause fatigue, dizziness, fainting, or blurred vision.
Do not drive or operate tools or machinery if you experience any of these symptoms. Exercise particular caution even if these effects do not occur.

3. How to use Bortezomib Sandoz BV

Your doctor will calculate the dose of Bortezomib Sandoz BV based on your height and weight (body surface area). The standard starting dose of Bortezomib Sandoz BV is 1.3 mg/m² of 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 side effects, and your overall health condition (e.g. liver problems).

Relapsed multiple myeloma
When Bortezomib Sandoz BV is given alone, you will receive 4 doses of Bortezomib Sandoz BV 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 of treatment).

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

When Bortezomib Sandoz BV is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib Sandoz BV given intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day Bortezomib Sandoz BV treatment cycle as an intravenous infusion after the injection of Bortezomib Sandoz BV.

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

When Bortezomib Sandoz BV is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Sandoz BV given intravenously or subcutaneously, and oral dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib Sandoz BV treatment cycle.

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

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and you are not eligible for stem cell transplantation, you will receive Bortezomib Sandoz BV intravenously 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 of treatment).

• During cycles 1–4, Bortezomib Sandoz BV is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5–9, Bortezomib Sandoz BV 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 never been treated before for multiple myeloma and you are eligible for stem cell transplantation, you will receive Bortezomib Sandoz BV intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

When Bortezomib Sandoz BV is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Sandoz BV given intravenously or subcutaneously, and oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Sandoz BV treatment cycle.

You will receive 4 cycles (12 weeks of treatment).

When Bortezomib Sandoz BV is administered together with thalidomide and dexamethasone, the treatment cycle lasts 28 days (4 weeks).

Oral dexamethasone 40 mg is administered on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day treatment cycle with Bortezomib Sandoz BV, and thalidomide is administered orally 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 may subsequently be increased up to 200 mg daily starting from the second cycle onward.

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

Previously untreated mantle cell lymphoma
If you have never previously received treatment for mantle cell lymphoma, you will receive Bortezomib Sandoz BV intravenously or subcutaneously in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Sandoz BV is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a treatment-free "rest" period. The duration of one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks of treatment).

The following medicines are administered on day 1 of each 21-day Bortezomib Sandoz BV treatment cycle as intravenous infusions:
rituximab at 375 mg/m², cyclophosphamide at 750 mg/m², and doxorubicin at 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 Sandoz BV treatment cycle.

How Bortezomib Sandoz BV is administered
This medicine is for intravenous or subcutaneous use. Bortezomib Sandoz BV will be administered by a healthcare professional experienced in the use of cytotoxic medicines.

The Bortezomib Sandoz BV powder must be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then injected into a vein or under the skin.
The intravenous injection is rapid, administered over a period of 3 to 5 seconds. The subcutaneous injection can be given either in the thigh or the abdomen.

If you are given too much Bortezomib Sandoz BV
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive too much. In the unlikely event of an overdose, your doctor will monitor you for side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some of these side effects can be serious.
If you are administered Bortezomib Sandoz BV 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 disturbances of vision, blindness, seizures, headache
• Shortness of breath, swelling of the feet or changes in heartbeat, high blood pressure, fatigue, fainting
• Cough and difficulty breathing or chest tightness.

Treatment with Bortezomib Sandoz BV can 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 Sandoz BV to monitor your blood cell counts regularly. You may experience a reduction in the number of:

• Platelets, which could make you more prone to bruising or bleeding without obvious injury (for example, bleeding from the intestine, stomach, mouth and gums, or brain or liver haemorrhage)
• Red blood cells, which can cause anaemia, with symptoms such as fatigue and paleness
• White blood cells, which may increase your susceptibility to infections or flu-like symptoms.

If you are administered Bortezomib Sandoz BV for the treatment of multiple myeloma, the possible side effects are listed below:
Very common side effects (may affect more than 1 in 10 people)

• Skin sensitivity, numbness, tingling or burning sensation of the skin, or pain in hands or feet due to nerve damage.
• Reduction in the number of red and/or white blood cells (see above).
• Fever.
• Nausea or vomiting, loss of appetite.
• Constipation with or without swelling (can be severe).
• Diarrhoea: if this occurs, it is important that you drink more water than usual. Your doctor may prescribe another medicine to control diarrhoea.
• Tiredness (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, which may lead to fainting.
• High blood pressure.
• Reduced kidney function.
• Headache.
• General feeling of discomfort, pain, dizziness, feeling of emptiness in the head, 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 disseminated throughout the body).
• Chest pain or shortness of breath during physical activity.
• Various types of skin rash.
• Itching of the skin, skin nodules or dry skin.
• Facial flushing or small capillary ruptures.
• Skin redness.
• Dehydration.
• Heartburn, bloating, belching, gas, stomach pain, bleeding from the intestine or stomach.
• Changes in liver function.
• Irritation of the mouth or lips, 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.
• Sleep difficulties or problems, 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 side effects (may affect up to 1 in 100 people)

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• Kidney failure.
• Inflammation of a vein, blood clots in veins and lungs.
• Blood clotting problems.
• Circulatory failure.
• Inflammation of the membrane surrounding the heart or fluid accumulation around the heart.
• Infections including urinary tract infections, influenza, herpes virus infections, ear infections, and cellulitis.
• Blood in the stool, or mucosal bleeding, for example from the mouth or vagina.
• Cerebrovascular disorders.
• Paralysis, seizures, falls, movement disorders, abnormal, altered or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, spasms.
• Arthritis, including inflammation of the joints of the fingers, toes and jaw.
• Lung disorders that impair the body's ability to receive sufficient oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath even without physical activity, shallow, laboured or interrupted breathing, wheezing.
• Hiccups, speech disorders.
• Increased or decreased urine production (due to kidney damage), painful urination, or presence of blood/protein in the urine, fluid retention.
• Altered levels of consciousness, confusion, impaired or loss of memory.
• Hypersensitivity.
• Hearing loss, deafness or ringing in the ears, ear discomfort.
• Hormonal changes that may affect the reabsorption of salts and water.
• Overactivity of the thyroid gland.
• Inability to produce enough insulin or resistance to normal insulin levels.
• Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, cysts on the eyelid (chalazion), red and swollen eyelids, eye discharge, vision disorders, eye bleeding.
• Enlargement of lymph nodes.
• Joint or muscle stiffness, feeling of heaviness, groin pain.
• Hair loss or abnormal hair texture.
• Allergic reactions.
• Redness or pain at the injection site.
• Mouth pain.
• Infection or inflammation of the mouth, mouth ulcers, oesophagus, stomach and intestine, sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting with blood.
• Skin infections.
• Bacterial and viral infections.
• Dental infections.
• Pancreatitis, obstruction of bile ducts.
• Genital pain, erectile problems.
• Weight gain.
• Feeling of thirst.
• Hepatitis.
• Injection site or device site reactions or disorders.
• Skin reactions or disorders (which can be severe and life-threatening), skin ulcerations.
• Bruising, falls and injuries.
• Inflammation or bleeding of blood vessels, which may present as small red or purple spots (usually on the legs) that may develop into large bruises under the skin or tissues.
• Benign cysts.
• A serious but reversible brain condition including seizures, high blood pressure, headache, fatigue, confusion, blindness or other vision problems.

Rare side effects (may affect up to 1 in 1,000 people)

• Heart problems including heart attack, angina.
• Hot flushes.
• Change in the colour of veins.
• Inflammation of the spinal nerve.
• Ear problems, bleeding from the ear.
• Reduced activity of the thyroid gland.
• Budd-Chiari syndrome (clinical signs are caused by blockage of the liver veins).
• Change or abnormal intestinal function.
• Cerebral haemorrhage.
• Yellowing of the eyes and skin (jaundice).
• Severe allergic reaction (anaphylactic shock), signs include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, swelling of the face, lips, tongue and/or throat which may cause difficulty swallowing, collapse.
• Breast disorders.
• Vaginal discharge.
• Swelling of the genitals.
• Inability to tolerate alcohol consumption.
• Wasting or loss of body mass.
• Increased appetite.
• Fistulas.
• Joint effusion.
• Cysts in the membrane covering the joints (synovial cysts).
• Fractures.
• Muscle fibre rupture leading to further complications.
• Enlarged liver, liver haemorrhage.
• Kidney cancer.
• Skin condition similar to psoriasis.
• Skin tumour.
• Pale skin.
• Increased platelets or plasma cells (a type of white blood cell) in the blood.
• Abnormal reaction to blood transfusion.
• Partial or complete loss of vision.
• Decreased sexual desire.
• Loss of saliva.
• Protruding eyes.
• Light sensitivity.
• Rapid breathing.
• Rectal pain.
• Gallstones.
• Hernia.
• Injuries.
• Brittle or weak nails.
• Abnormal deposition of proteins in vital organs.
• Coma.
• Intestinal ulcers.
• Multi-organ failure.
• Death.
• Blood clot in small blood vessels (thrombotic microangiopathy).

If you are administered Bortezomib Sandoz BV in combination with other medicines for the treatment of mantle cell lymphoma, the possible side effects are listed below.
Very common side effects (may affect more than 1 in 10 people):

• Pneumonia.
• Loss of appetite.
• Skin sensitivity, numbness, tingling or burning sensation of the skin, or pain in hands or feet due to nerve damage.
• Nausea and vomiting.
• Diarrhoea.
• Mouth ulcers.
• Constipation.
• Muscle pain, bone pain.
• Hair loss and abnormal hair texture.
• Tiredness, feeling of weakness.
• Fever.

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

• Herpes zoster (localized, including around the eyes, or disseminated 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 enough insulin or resistance to normal insulin levels.
• Fluid retention.
• Sleep difficulties or problems.
• Loss of consciousness.
• Altered levels 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 may lead to fainting.
• Shortness of breath during physical activity.
• Cough.
• Hiccups.
• Ringing in the ears, ear discomfort.
• Intestinal or stomach bleeding.
• Heartburn.
• Stomach pain, bloating.
• Difficulty swallowing.
• Infection or inflammation of the stomach and intestine.
• Stomach pain.
• Irritation of the mouth or lips, sore throat.
• Changes in liver function.
• Itching of the skin.
• Skin redness.
• 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.
• Loss of body weight.
• Increase in body weight.

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

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction), signs of which may include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, swelling of the face, lips, tongue and/or throat which may cause difficulty swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Dizziness.
• Hearing loss, deafness.
• Lung disorders that impair the body's ability to receive sufficient oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath even without physical activity, shallow, laboured or interrupted breathing, wheezing.
• Blood clots in the lungs.
• Yellowing of the eyes and skin (jaundice).
• Cysts on the eyelid (chalazion), red and swollen eyelids.

Rare side effects (may affect up to 1 in 1,000 people)

• Blood clot in small blood vessels (thrombotic microangiopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bortezomib Sandoz BV

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 vial and carton following
Exp. The expiry date refers to the last day of that month.
Store the vial in the outer packaging to protect the medicine from light.
This medicine does not require any special storage temperature conditions.

Reconstituted solution
Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C /60% RH when stored
in the dark in either a vial or a polypropylene syringe.
From a microbiological standpoint, the product should be used immediately, unless the reconstitution/
dilution method prevents the risk of microbial contamination.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the
user.
Bortezomib Sandoz BV is for single use only. Any unused product and waste materials resulting from
this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What Bortezomib Sandoz BV contains
The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol boronic ester).
The other component is mannitol (E421).

Reconstitution for intravenous use:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.

Reconstitution for subcutaneous use:
After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

Description of the appearance of Bortezomib Sandoz BV and contents of the pack
Bortezomib Sandoz BV for injection concentrate powder is a white to off-white powder.
Bortezomib Sandoz BV is supplied in a glass vial with a rubber stopper and a blue flip-off cap.
Each pack contains 1 single-use vial.

Marketing Authorization Holder
Sandoz BV
Veluwezoom 22
1327 AH Almere
The Netherlands
Legal representative in Italy: Sandoz S.p.A., L.go U. Boccioni 1, 21040 Origgio (VA), Italy

Manufacturer
Synthon Hispania SL
C/ Castelló no 1, Pol. Las Salinas, Sant Boi de Llobregat, 08830, Barcelona, Spain
Synthon s.r.o.
Brněnská 32/čp. 597, 678 01, Blansko, Czech Republic
Sandoz GmbH
Biochemiestraße 10
6250 Kundl
Austria
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben
Sachsen-Anhalt
Germany

This medicinal product is authorized in the European Economic Area (EEA) Member States under the following names:
Austria Bortezomib Sandoz 3.5 mg - Powder for solution for injection
Belgium Bortezomib Sandoz 3.5 mg powder for solution for injection
Bulgaria Бортезомиб Сандоз 3.5 mg прах за инжекционен разтвор
Denmark Bortezomib Sandoz
Finland Bortezomib Sandoz 3.5 mg for injection, powder for solution
France BORTEZOMIB SANDOZ 3.5 mg, powder for solution for injection
Germany Bortezomib Hexal 3.5 mg
Greece Bortezomib/Sandoz
Italy Bortezomib Sandoz BV
Ireland Bortezomib Rowex 3.5 mg Powder for solution for injection
Iceland Bortezomib Sandoz stungulyfsstofn, lausn
Norway Bortezomib Sandoz
The Netherlands Bortezomib Sandoz 3.5 mg, powder for solution for injection
Poland Bortezomib Sandoz
Portugal Bortezomib Sandoz Farmacêutica
United Kingdom Bortezomib Sandoz 3.5 mg powder for solution for injection
Czech Republic Bortezomib Sandoz
Slovakia Bortezomib Sandoz
Romania Bortezomib Sandoz 3.5 mg, powder for solution for injection
Slovenia Bortezomib Sandoz 3.5 mg for injection, powder for solution
Spain Bortezomib Sandoz 3.5 mg powder for solution for injection EFG
Sweden Bortezomib Sandoz 3.5 mg powder for injection solution
Hungary Bortezomib Sandoz 3.5 mg por oldatos injekcióhoz

The following information is intended exclusively for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Sandoz BV is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, STRICT ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB SANDOZ BV.
1.1 Preparation of the 3.5 mg vial: carefully add 3.5 ml of sterile sodium chloride 9 mg/ml (0.9%) solution for injection to the vial containing the Bortezomib Sandoz BV lyophilized powder, using an appropriate syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution will be 1 mg/ml. The solution will be clear and colourless, with a final pH between 4 and 7. Testing of the solution pH is not required.
1.2 Visually inspect the solution before administration to check for the presence of particulate matter or any discolouration. If discolouration or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The reconstituted solution contains no preservatives and must be used immediately after preparation. However, chemical and physical in-use stability has been demonstrated for 8 hours at 25°C /60% RH when stored protected from light, either in the original vial and/or in a syringe.
From a microbiological standpoint, the product should be used immediately unless the reconstitution/dilution method precludes the risk of microbial contamination.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume 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 (check that the syringe is labeled for intravenous administration).
• Administer the solution as an intravenous bolus injection over 3–5 seconds through a peripheral or central intravenous catheter into a vein.
• Flush the peripheral or intravenous catheter with sterile 9 mg/ml (0.9%) sodium chloride solution.

Bortezomib Sandoz BV 3.5 mg powder for injectable solution IS FOR
SUBCUTANEOUS OR INTRAVENOUS USE ONLY. Do not administer by other routes.
Intrathecal administration of bortezomib has resulted in deaths.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with
applicable local regulations.
The following information is intended exclusively for healthcare professionals:
Only the 3.5 mg vial can be administered by subcutaneous route, as described below:

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Sandoz BV is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, STRICT ASEPTIC TECHNIQUE MUST BE FOLLOWED DURING THE HANDLING OF BORTEZOMIB SANDOZ BV.
1.1 Preparation of the 3.5 mg vial: carefully add 1.4 ml of sterile sodium chloride 9 mg/ml (0.9%) for injection to the vial containing the Bortezomib Sandoz BV lyophilized powder using an appropriate syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution will be 2.5 mg/ml. The solution will be clear and colourless, with a final pH between 4 and 7. There is no need to check the pH of the solution.
1.2 Visually inspect the solution before administration to check for the presence of particulate matter or discoloration. If discoloration or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered by subcutaneous route (2.5 mg/ml).
1.3 The reconstituted solution contains no preservatives and must be used immediately after preparation. However, chemical and physical in-use stability has been demonstrated for 8 hours at 25°C /60% RH when stored in the dark, either in the original vial and/or in a syringe. The total storage time for the reconstituted medicinal product must not exceed 8 hours prior to administration.
From a microbiological standpoint, the product should be used immediately, unless the reconstitution/dilution method excludes the risk of microbial contamination.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.

2. ADMINISTRATION

• After dissolution, withdraw the appropriate volume 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 (check that the syringe is labeled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The reconstituted solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left side).
• For subsequent administrations, rotate the injection site.
• If local reactions occur at the injection site after subcutaneous administration of Bortezomib Sandoz BV, a lower concentration of Bortezomib Sandoz BV solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

Bortezomib Sandoz BV 3.5 mg powder for injectable solution FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. Do not administer by other routes. Intrathecal administration
of bortezomib has resulted in deaths.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with
applicable local regulations.