Bortezomib EG

Package leaflet: Information for the user

BORTEZOMIB EG 2.5 mg/ml solution for injection

Generic medicine
Please read all of this leaflet carefully before you are given 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, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What BORTEZOMIB EG is and what it is used for
2. What you need to know before you are given BORTEZOMIB EG
3. How BORTEZOMIB EG is given
4. Possible side effects
5. How to store BORTEZOMIB EG
6. Contents of the pack and other information

1. What BORTEZOMIB EG is and what it is used for

BORTEZOMIB EG contains the active substance bortezomib, a so-called "proteasome inhibitor".
Proteasomes play an important role in controlling cell functions and cell growth. By interfering with their function, bortezomib can kill tumour cells.

BORTEZOMIB EG is used to treat 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 or in whom blood stem cell transplantation has failed or is not feasible;
• in combination with melphalan and prednisone, for previously untreated patients who are not eligible for high-dose chemotherapy with blood stem cell transplantation;
• in combination with dexamethasone or dexamethasone plus thalidomide, for previously untreated patients prior to receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment).

BORTEZOMIB EG 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 taking BORTEZOMIB EG

DO NOT use BORTEZOMIB EG

• 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
Inform your doctor if:

• you have a reduced number of red or white blood cells;
• you have bleeding problems and/or low platelet count in the blood;
• you have diarrhoea, constipation, nausea, or vomiting;
• you have previously experienced fainting, dizziness, or a feeling of lightheadedness;
• you have kidney problems;
• you have moderate to severe liver problems;
• you have previously had numbness, tingling, or pain in your hands or feet (neuropathy);
• you have a heart condition or blood pressure problems;
• you have shortness of breath or cough;
• you have seizures;
• you have shingles (including localized around the eyes or widespread throughout the body);
• symptoms of tumour lysis syndrome such as muscle cramps, muscle weakness, confusion, vision disturbances, or 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 carry out further tests and monitoring.

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

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

Read the package leaflets of all the medicines you are taking in combination with BORTEZOMIB EG for information about these medicines before starting treatment with BORTEZOMIB EG.
When thalidomide is administered, special attention must be paid to pregnancy testing and pregnancy prevention measures (see Pregnancy and breastfeeding in this section).

Children and adolescents
BORTEZOMIB EG must not be used in children and adolescents because it is not known how the medicine works in these individuals.

Other medicines and BORTEZOMIB EG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, tell 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 EG during pregnancy unless strictly necessary.
Men and women undergoing treatment with BORTEZOMIB EG must use effective contraception 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 EG. Discuss with your doctor the appropriate time to resume breastfeeding after treatment ends.
The medicine thalidomide causes congenital malformations and fetal death. When BORTEZOMIB EG is administered together with thalidomide, you must follow the thalidomide pregnancy prevention programme (see the thalidomide package leaflet).

Driving and using machines
BORTEZOMIB EG may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate machinery if you experience any of these symptoms. Exercise particular caution even if these effects are not apparent.

BORTEZOMIB EG contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore essentially "sodium-free".

3. How to use BORTEZOMIB EG

Your doctor will calculate the dose of BORTEZOMIB EG based on your height and weight (body surface area). The initial standard dose of BORTEZOMIB EG 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 adverse effects, and your overall health condition (e.g. liver problems).

Relapsed multiple myeloma
When BORTEZOMIB EG is given alone, you will receive 4 doses of BORTEZOMIB EG 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).

You may also receive BORTEZOMIB EG in combination with pegylated liposomal doxorubicin or dexamethasone.

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

When BORTEZOMIB EG is administered together with dexamethasone, you will receive a 21-day treatment cycle with BORTEZOMIB EG 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 EG treatment cycle. You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and are not eligible for autologous stem cell transplantation, you will receive BORTEZOMIB EG 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 1–4, BORTEZOMIB EG is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5–9, BORTEZOMIB EG 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 are eligible for autologous stem cell transplantation, you will receive BORTEZOMIB EG intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

When BORTEZOMIB EG is administered together with dexamethasone, you will receive a 21-day treatment cycle with BORTEZOMIB EG 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 EG treatment cycle. You will receive 4 cycles (12 weeks).

When BORTEZOMIB EG is administered together with thalidomide and dexamethasone, the treatment cycle duration 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 EG treatment cycle, and thalidomide is administered daily orally 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 onwards. You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If you have never previously received specific treatment for mantle cell lymphoma, you will receive BORTEZOMIB EG intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
BORTEZOMIB EG is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest" period without treatment. The treatment cycle duration is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

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

How BORTEZOMIB EG is administered
This medicine is for subcutaneous use and, after dilution, also for intravenous use.
BORTEZOMIB EG will be administered by a healthcare professional experienced in the use of cytotoxic medicines.
The solution is then injected into a vein or under the skin. The intravenous injection is rapid, taking between 3 and 5 seconds. The subcutaneous injection can be administered either in the thigh or the abdomen.

If you are given too much BORTEZOMIB EG
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive more than intended. In the unlikely event of an overdose, your doctor will monitor you for adverse 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 EG for multiple myeloma or mantle cell lymphoma, inform your doctor immediately if you notice any of the following symptoms:

• Muscle cramps, muscle weakness;
• Confusion, vision disturbances or loss 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 EG 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 EG to monitor your blood cell counts. You may experience a reduction in the number of:

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

If you are administered BORTEZOMIB EG 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)

• Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the 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 excessive intestinal gas (may be severe);
• Diarrhoea: if this occurs, it is important that you drink much more water than usual. Your doctor may prescribe medication to control diarrhoea;
• Fatigue (tiredness), 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 upon standing which may lead to fainting;
• High blood pressure;
• Reduced kidney function;
• Headache;
• General malaise, pain, dizziness, feeling of emptiness in the head, weakness or loss of consciousness;
• Chills;
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, productive cough, flu-like illness;
• Herpes zoster (may be localized around the eyes or spread to other parts of the body);
• Chest pain or difficulty breathing during physical activity;
• Various types of skin rash;
• Itchy skin, skin nodules or dry skin;
• Facial flushing or small capillary ruptures;
• Skin redness;
• Dehydration;
• Heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding;
• Altered liver function;
• Mouth or lip pain, dry mouth, oral 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 disturbances 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;
• Vein inflammation, 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 infection, and cellulitis;
• Blood in the stool, or mucosal bleeding (e.g. mouth, vagina);
• Cerebrovascular disorders;
• Paralysis, seizures, falls, movement disorders, abnormal or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, spasms;
• Arthritis, including inflammation of the joints of fingers, toes, and jaw;
• Lung disorders that prevent your body from receiving sufficient oxygen. These may include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow breathing difficulty or need to stop, wheezing;
• Hiccups, speech disorders;
• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in urine, fluid retention;
• Altered levels of consciousness, confusion, memory impairment or loss;
• Hypersensitivity;
• Hearing loss, deafness or ringing in the ears (tinnitus), ear discomfort;
• Hormonal disturbances affecting 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, eye discharge, vision disturbances, eye bleeding;
• Swollen 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, oesophageal, stomach or intestinal ulcers sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal obstruction), 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 dysfunction;
• Weight gain;
• Thirst;
• Hepatitis;
• Injection site or catheter site reactions;
• Skin reactions or disorders (which may be severe and potentially fatal), skin ulcerations;
• Bruising, falls and injuries;
• Inflammation or haemorrhage of blood vessels, which may present as small red or purple spots (usually on the legs) that may develop into large bruises on 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 pectoris;
• Flushing;
• Change in vein colour;
• Spinal nerve inflammation;
• Ear problems, ear bleeding;
• Reduced thyroid gland activity;
• Budd-Chiari syndrome (clinical signs caused by blockage of the liver veins);
• Altered or abnormal intestinal function;
• Cerebral haemorrhage (bleeding);
• Yellowing of the eyes and skin (jaundice);
• Severe allergic reaction (anaphylactic shock): signs include difficulty breathing, chest pain or tightness, and/or dizziness/fainting, severe skin itching or skin swellings, facial, lip, tongue and/or throat swelling that 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;
• Fistula;
• 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 cancer;
• Pallor of the 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 libido;
• Loss of saliva;
• Protruding eyes;
• Light sensitivity;
• Rapid breathing;
• Rectal pain;
• Gallstones;
• Hernia;
• Injuries;
• Brittle or weak nails;
• Abnormal protein deposition in vital organs;
• Coma;
• Intestinal ulcers;
• Multi-organ failure;
• Death.

If you are administered BORTEZOMIB EG 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;
• Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet due to nerve damage;
• Nausea and vomiting;
• Diarrhoea;
• Oral ulcers;
• Constipation;
• Muscle pain, bone pain;
• Hair loss or abnormal hair texture;
• Fatigue, feeling of weakness;
• Fever.

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

• Herpes zoster (may be localized around the eyes or spread to other parts of the body);
• Herpes virus infection;
• Bacterial and viral infections;
• Respiratory infections, bronchitis, productive cough, flu-like illness;
• Fungal infections;
• Hypersensitivity (allergic reaction);
• Inability to produce enough insulin or resistance to normal insulin levels;
• Fluid retention;
• Difficulty or problems sleeping;
• Loss of consciousness;
• Altered levels of consciousness, confusion;
• Dizziness;
• Increased heart rate, high blood pressure, sweating;
• Vision disturbances, blurred vision;
• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate;
• Low or high blood pressure;
• Sudden drop in blood pressure upon standing which may lead to fainting;
• Shortness of breath during physical activity;
• Cough;
• Hiccups;
• Ringing in the ears (tinnitus), ear discomfort;
• Intestinal or stomach bleeding;
• Heartburn;
• Stomach pain, bloating;
• Difficulty swallowing;
• Infection or inflammation of the stomach and intestine;
• Stomach pain;
• Mouth or lip pain, sore throat;
• Altered liver function;
• Itchy 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 or pain at the injection site;
• General feeling of malaise;
• Weight loss;
• Weight gain.

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

• Hepatitis;
• Severe allergic reaction (anaphylactic shock): signs include difficulty breathing, chest pain or tightness, and/or dizziness/fainting, severe skin itching or skin swellings, facial, lip, tongue and/or throat swelling that may cause difficulty swallowing, collapse;
• Movement disorders, paralysis, contractions;
• Dizziness;
• Hearing loss, deafness;
• Lung disorders that prevent your body from receiving sufficient oxygen. These may include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow breathing difficulty or need to stop, wheezing;
• Blood clots in the lungs;
• Yellowing of the eyes and skin (jaundice).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
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 EG

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 on the packaging following the term EXP.
Store the unopened vial in a refrigerator (2 °C – 8 °C). Keep the vial in its outer container to protect the product from light.
The diluted solution should be used immediately after reconstitution. If the diluted solution is not used immediately, the storage times and conditions prior to use are the responsibility of the user. In any case, the diluted solution remains stable for 8 hours at 25°C when stored in the original vial and/or in a polypropylene syringe, with a total storage time for the diluted medicine not exceeding 8 hours before administration.
With regard to stability within the syringe, the same storage times apply to both diluted and undiluted solutions.
BORTEZOMIB EG is for single use only. Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What BORTEZOMIB EG contains

• The active substance is bortezomib. Each vial contains 1.4 ml of injectable solution with 3.5 mg of bortezomib (as mannitol boronic ester).
• The other ingredients are mannitol, sodium chloride, water for injectable preparations.

For intravenous use: After dilution, 1 ml of intravenous solution contains 1 mg of
bortezomib.
For subcutaneous use: 1 ml of subcutaneous solution contains 2.5 mg of
bortezomib.
Description of the appearance of BORTEZOMIB EG and contents of the pack
BORTEZOMIB EG injectable solution is a clear, colourless or slightly yellow solution.
Each pack of BORTEZOMIB EG 2.5 mg/ml injectable solution contains one 10 ml glass vial with a coloured flip-off cap made of polypropylene.
Marketing Authorisation Holder
EG S.p.A., via Pavia 6, 20136 Milano
Manufacturer
STADA Arzneimittel AG, Stadastrasse 2 – 18, 61118 Bad Vilbel - Germany
STADAPHARM GmbH, Feodor-Lynen-Straße 35, 30625 Hannover - Germany
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
AT Bortezomib STADA 2.5 mg/ml Injektionslösung
BE Bortezomib EG 2.5 mg/ml oplossing voor injectie
DE Bortezomib STADA 2.5 mg/ml Injektionslösung
DK Bortezomib STADA
ES Bortezomib STADA 2.5 mg/ml solución inyectable
FI Bortezomib STADA 2.5 mg/ml injektioneste, liuos
FR Bortezomib EG 2.5 mg/ml solution injectable
IE Bortezomib Clonmel 2.5 mg/ml solution for injection
IT BORTEZOMIB EG
LU Bortezomib EG 2.5 mg/ml solution injectable
NL Bortezomib CF 2.5 mg/ml, oplossing voor injectie
PL Bortezomib Stada
SE Bortezomib STADA 2.5 mg/ml injektionsvätska, lösning
SI Bortezomib STADA 2.5 mg/ml raztopina za injiciranje
SK Bortezomib STADA
________________________________________________________________________
The following information is intended exclusively for physicians or healthcare professionals:

1. PREPARATION OF THE INTRAVENOUS INJECTION

Pregnant personnel must not handle this medicinal product.
Note: BORTEZOMIB EG is a cytotoxic agent. Therefore, 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, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED DURING THE HANDLING OF BORTEZOMIB EG.
1.1 Reconstitution of the 3.5 mg vial: add 2.1 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing BORTEZOMIB EG.
The concentration of the resulting solution is 1 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 The solution must be inspected visually before administration to check for the presence of particles or any colour change. If particles or a colour change are observed, the solution must be discarded. Ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The diluted solution is preservative-free and must be used immediately after preparation. However, the chemical and physical in-use stability of the diluted solution has been demonstrated for 8 hours at 25°C in the original vial and/or in a polypropylene syringe. The total storage time of the reconstituted medicinal product must not exceed 8 hours before administration. If the reconstituted solution is not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.
There is no need to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

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

BORTEZOMIB EG 2.5 mg/ml solution for injection is INTENDED FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. Do not administer by other routes.
INTRATHECAL ADMINISTRATION HAS RESULTED IN PATIENT DEATH.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused product or waste material must be disposed of in accordance with local regulations concerning cytotoxic products.
The following information is intended exclusively for physicians or healthcare professionals:

1. PREPARATION OF THE SUBCUTANEOUS INJECTION

Pregnant personnel must not handle this medicinal product.
Note: BORTEZOMIB EG is a cytotoxic agent. Therefore, 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 KIND OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED DURING THE HANDLING OF BORTEZOMIB EG.
1.1 BORTEZOMIB EG is ready for use.
The concentration of the resulting solution is 2.5 mg/ml. The solution will be clear and colourless with a pH between 4.0 and 5.5. It is not necessary to check the pH of the solution.
1.2 The solution should be inspected visually before administration to check for the presence of particles or any change in colour. If particles or discolouration are present, the solution must be discarded. Ensure that the correct dose is administered by subcutaneous route (2.5 mg/ml).
1.3 The product contains no preservatives and must be used immediately after withdrawal of the appropriate volume of solution. However, the chemical and physical in-use stability of the solution has been demonstrated for 8 hours at 25°C in the original vial and/or in a polypropylene syringe. The total storage time of the medicinal product must not exceed 8 hours prior to administration. If the solution is not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.
During preparation for administration and during administration itself, it is not necessary to protect the medicinal product from light.

2. ADMINISTRATION

• Withdraw the appropriate volume 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 (check that the syringe is labeled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left).
• Injection sites should be rotated with each subsequent injection.
• If local reactions occur at the injection site after subcutaneous administration of BORTEZOMIB EG, a lower concentration of BORTEZOMIB EG solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or intravenous injection is recommended.

BORTEZOMIB EG 2.5 mg/ml solution for injection is FOR SUBCUTANEOUS OR INTRAVENOUS USE ONLY.
DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN PATIENT DEATH.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused product or waste material must be disposed of in accordance with local regulations regarding cytotoxic products.