Bortezomib Eugia

Leaflet accompanying the packaging: patient information

Bortezomib Eugia, 3.5 mg, powder for solution for injection

Bortezomib

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Bortezomib Eugia and what is it used for
• 2. Important information before using Bortezomib Eugia
• 3. How to use Bortezomib Eugia
• 4. Possible side effects
• 5. How to store Bortezomib Eugia
• 6. Package contents and other information

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

Bortezomib Eugia contains the active substance bortezomib, which is a so-called proteasome inhibitor. Proteasomes play a crucial role in controlling cell function and development. By disrupting their function, bortezomib can lead to the death of cancer cells.
Bortezomib Eugia is used to treat multiple myeloma (bone marrow cancer) in patients aged 18 and over:

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

Bortezomib Eugia is used to treat mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged 18 and over in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, who have not been previously treated and are not eligible for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Eugia

When not to use Bortezomib Eugia

• If the patient is allergic to bortezomib, boron, or any of the other ingredients of this medicine (listed in section 6).
• If the patient has severe lung or heart disease.

Warnings and precautions

The patient should inform their doctor if they:

• have a low red or white blood cell count;
• have bleeding disorders and (or) a low platelet count;
• experience diarrhea, constipation, nausea, or vomiting;
• have a history of fainting, dizziness, and lightheadedness;
• have kidney disease;
• have moderate to severe liver function disorders;
• have a history of numbness, tingling, and pain in the hands and feet (symptoms of neuropathy);
• have heart disease or blood pressure problems;
• have shortness of breath or cough;
• experience seizures;
• have shingles (around the eyes or widespread on the body);
• experience symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, loss of vision, and shortness of breath;
• experience memory loss, thinking disorders, difficulty walking, or loss of vision. These may be symptoms of a severe brain infection, and the doctor may recommend further tests and observation.

The patient must have regular blood tests before and during treatment with Bortezomib Eugia to regularly check their blood cell count.
If the patient has mantle cell lymphoma and is receiving Bortezomib Eugia with rituximab, they should tell their doctor:

• if they suspect or have had hepatitis B virus infection in the past. In a few cases, patients who had hepatitis B virus infection may have had recurring episodes of hepatitis, which could be fatal. If the patient has a history of hepatitis B virus infection, they will be closely monitored by their doctor for signs of active hepatitis B virus infection.

Before starting treatment with Bortezomib Eugia, the patient should carefully read the leaflets of all medicines they are taking during treatment to obtain information about them.
If the patient is taking thalidomide, they should exclude pregnancy and then use effective contraception (see section Pregnancy and breastfeeding).

Children and adolescents

Bortezomib Eugia should not be used in children and adolescents, as its effects in this patient group are unknown.

Bortezomib Eugia and other medicines

The patient should tell their doctor about all medicines they are currently taking or plan to take.
In particular, the patient should inform their doctor if they are taking medicines containing any of the following active substances:

• ketokonazole, used to treat fungal infections;
• ritonavir, used to treat HIV infection;
• rifampicin, an antibiotic used to treat bacterial infections;
• carbamazepine, phenytoin, or phenobarbital for the treatment of epilepsy;
• St. John's Wort (Hypericum perforatum) for the treatment of depression and other conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding

Bortezomib Eugia should not be used during pregnancy, unless it is absolutely necessary.
Both men and women receiving Bortezomib Eugia must use effective contraception methods during and for 3 months after completing treatment. If, despite using these methods, the patient becomes pregnant, they should immediately inform their doctor.
Patients should not breastfeed while taking Bortezomib Eugia. It is necessary to discuss with the doctor the issue of a safe return to breastfeeding after completing treatment in the patient.
Thalidomide causes birth defects and fetal death. In the case of using Bortezomib Eugia in combination with thalidomide, patients must follow the rules of the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and operating machinery

Bortezomib Eugia may cause fatigue, dizziness, fainting, and blurred vision. If these symptoms occur, the patient should not drive vehicles or operate tools or equipment; even if the symptoms do not occur, the patient should still exercise caution.

3. How to use Bortezomib Eugia

The doctor will adjust the appropriate dose of Bortezomib Eugia for the patient based on their height and weight (body surface area). The most commonly used initial dose of Bortezomib Eugia is 1.3 mg/m2 (body surface area) administered twice a week.
The doctor may change the dose and total number of treatment cycles depending on the patient's response to treatment, the occurrence of side effects, and additional diseases (e.g., liver disease).

Progressive multiple myeloma

If Bortezomib Eugia is administered as a single medicine, the patient will receive 4 doses of Bortezomib Eugia intravenously or subcutaneously on days: 1, 4, 8, and 11, followed by a 10-day break in treatment.
The described 21-day period (3 weeks) is considered one treatment cycle. The patient will receive up to 8 cycles (24 weeks).
The patient may also receive Bortezomib Eugia in combination with pegylated liposomal doxorubicin or dexamethasone.
When Bortezomib Eugia is administered in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Eugia intravenously or subcutaneously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m2 in an intravenous infusion after Bortezomib Eugia injection on day 4 of the 21-day cycle.
The patient may receive up to 8 cycles (24 weeks).
When Bortezomib Eugia is administered in combination with dexamethasone, the patient will receive Bortezomib Eugia intravenously or subcutaneously during a 21-day treatment cycle, and dexamethasone will be administered orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib Eugia treatment cycle. The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If the patient has not been previously treated for multiple myeloma and the patient does notqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Eugia in combination with melphalan and prednisone.
In this case, the treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1-4, Bortezomib Eugia is administered twice a week, on days: 1, 4, 8, 11, 22, 25, 29, and 32.
• 11, 22, 25, 29, and 32.
• During cycles 5-9, Bortezomib Eugia is administered once a week, on days: 1, 8, 22, and 29. Both 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.
• 3 and 4 of the first week of each cycle.

If the patient has not been previously treated for multiple myeloma and qualifies for hematopoietic stem cell transplantation, they will receive Bortezomib Eugia intravenously or subcutaneously in combination with dexamethasone or dexamethasone with thalidomide as induction treatment.
When Bortezomib Eugia is administered with dexamethasone, the patient will receive Bortezomib Eugia intravenously or subcutaneously during a 21-day cycle, and dexamethasone will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Eugia treatment cycle. The patient may receive up to 4 cycles (12 weeks).
When Bortezomib Eugia is administered with thalidomide and dexamethasone, the treatment cycle lasts 28 days (4 weeks).
Dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib Eugia treatment cycle, and thalidomide will be administered orally once a day at a dose of 50 mg until day 14 of the first cycle, and if the dose is tolerated, it will be increased to 100 mg on days 15-28 and may be further increased to 200 mg per day from the second cycle. The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If the patient has not been previously treated for mantle cell lymphoma, they will receive Bortezomib Eugia intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib Eugia is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without medication administration. One treatment cycle lasts 21 days (3 weeks).
The patient may receive up to 8 cycles (24 weeks).
The following medicines are administered as intravenous infusions on day 1 of each 21-day Bortezomib Eugia 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 Eugia treatment cycle.

How Bortezomib Eugia is administered

This medicine is administered intravenously or subcutaneously. Bortezomib Eugia will be administered by medical personnel with experience in the use of cytotoxic medicines. The Bortezomib Eugia powder must be dissolved before administration. The preparation of the medicine is carried out by medical personnel. The resulting solution is then injected intravenously or subcutaneously. Intravenous injection is performed quickly and lasts from 3 to 5 seconds.
Subcutaneous injection is administered in the thigh or abdomen.

Use of a higher than recommended dose of Bortezomib Eugia

The medicine is administered by a doctor or nurse, so it is unlikely that the patient will receive too high a dose of the medicine. If this happens, the doctor will monitor the patient for any side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of these side effects may be serious.
If the patient is receiving Bortezomib Eugia for multiple myeloma or mantle cell lymphoma, they should immediately tell their doctor if they experience any of the following symptoms:

• muscle cramps, muscle weakness;
• confusion, loss of vision, blindness, seizures, headaches;
• shortness of breath, swelling of the feet or changes in heart rhythm, high blood pressure, fatigue, fainting;
• cough and difficulty breathing or chest pressure.

Treatment with Bortezomib Eugia may very often cause a decrease in the patient's red and white blood cell count and platelet count. Therefore, the patient must have frequent blood tests before and during treatment with Bortezomib Eugia to regularly check their blood cell count. The patient may experience a decrease in:

• platelet count, which may lead to bruising or bleeding that is not caused by injury (e.g., gastrointestinal bleeding, bleeding from the mouth, gums, or nose, or brain hemorrhage);
• red blood cell count, which may lead to anemia, characterized by symptoms such as fatigue and paleness;
• white blood cell count, which may lead to increased susceptibility to infections or flu-like symptoms.

If the patient is receiving Bortezomib Eugia for multiple myeloma, they may experience the following side effects:

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

• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in the hands or feet caused by nerve damage
• decrease in red and (or) white blood cell count (see above)
• fever
• nausea or vomiting, loss of appetite
• constipation occurring with or without bloating (symptoms may be severe)
• diarrhea: if this happens, the patient should drink more water than usual, and the doctor may recommend taking additional medicines to control diarrhea
• 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 up, which may lead to fainting
• high blood pressure
• decreased kidney function
• headache
• general malaise, pain, dizziness, lightheadedness, feeling of weakness or loss of consciousness
• chills
• infections, including: pneumonia, respiratory tract infections, bronchitis, fungal infections, cough with sputum production, flu-like symptoms
• shingles (localized, e.g., around the eyes or widespread on the body)
• chest pain, shortness of breath during exercise
• various types of rash
• itching, skin rash, or dry skin
• flushing of the face or broken blood vessels
• redness of the skin
• dehydration
• heartburn, bloating, belching, gas, abdominal pain, gastrointestinal bleeding
• liver function disorders
• mouth or lip inflammation, dry mouth, mouth ulcers
• weight loss, loss of taste
• muscle cramps, muscle weakness, bone pain
• blurred vision
• conjunctivitis
• nosebleeds
• difficulty sleeping, sweating, anxiety, mood swings, depression, restlessness, or agitation, changes in mental state, disorientation
• swelling, including around the eyes and other parts of the body.

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

• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate
• kidney failure
• vein inflammation, blood clots in veins and lungs
• blood clotting disorders
• circulatory failure
• inflammation of the sac surrounding the heart (pericarditis) or fluid in the pericardium
• infections, including: urinary tract infections, flu, herpes, ear and soft tissue infections
• blood in the stool, bleeding from mucous membranes, e.g., mouth, vagina
• brain vessel disorders
• paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, tremors, twitching
• joint inflammation, including joint inflammation of the fingers, toes, and jaw
• lung disorders making breathing difficult. Some of these include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing, wheezing
• hiccups, speech disorders
• increased or decreased urine production (due to kidney damage), painful urination, or blood/protein in the urine, fluid retention
• altered level of consciousness, confusion, worsening or loss of memory
• allergic reactions
• hearing loss, deafness, ringing or discomfort in the ears
• hormonal disorders that can affect salt and water absorption
• hyperthyroidism
• insulin deficiency or resistance to normal insulin levels
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, stye (hordeolum), red and swollen eyelids, eye discharge, vision disorders, eye bleeding
• lymph node enlargement
• joint stiffness or muscle stiffness, feeling of heaviness, groin pain
• hair loss and abnormal hair structure
• allergic reactions
• redness or pain at the injection site
• mouth pain
• infections or inflammation of the mouth, esophagus, stomach, and intestines, sometimes with accompanying pain and bleeding, poor intestinal motility (including obstruction), abdominal discomfort, and esophageal discomfort, difficulty swallowing, vomiting blood
• skin infection
• bacterial and viral infections
• tooth infections
• pancreatitis, bile duct obstruction
• genital pain, erectile dysfunction
• weight gain
• thirst
• hepatitis
• disorders related to the injection site or use of a vascular catheter
• skin reactions and disorders (which can be severe and life-threatening), skin ulcers
• bruises, falls, and injuries
• inflammation or bleeding from blood vessels, manifested by small red or purple spots (usually on the legs) to large similar bruise-like spots under the skin
• benign cysts
• severe reversible brain disorders, which include seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disorders.

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

• heart disease, including heart attack, angina pectoris
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome)
• flushing
• vein discoloration
• spinal cord inflammation
• ear disorders, ear bleeding
• hypothyroidism
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins)
• abnormal or changed intestinal function
• brain bleeding
• jaundice (yellowing of the skin and eyes)
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, pain or pressure in the chest, and (or) feeling of dizziness/fainting, severe itching of the skin or hives, swelling of the face, lips, tongue, and (or) throat, which can cause difficulty breathing and swallowing, collapse
• breast disorders
• vaginal ulcers
• genital swelling
• alcohol intolerance
• weight loss or gain
• increased appetite
• fistula
• joint effusion
• synovial cyst (ganglion cyst)
• bone fractures
• muscle fiber breakdown leading to further complications
• liver swelling, liver bleeding
• kidney cancer
• skin condition similar to psoriasis
• skin cancer
• pale skin
• increased platelet count or plasma cells (a type of white blood cell)
• blood clots in small blood vessels (microangiopathic thrombosis)
• abnormal reaction to blood transfusion
• partial or complete loss of vision
• decreased libido
• excessive salivation
• exophthalmos
• photosensitivity
• increased respiratory rate
• rectal pain
• gallstones
• hernia
• injuries
• brittle or weak nails
• abnormal protein deposition in organs
• coma
• intestinal ulcers
• multi-organ failure
• death.

If the patient is receiving Bortezomib Eugia with other medicines for mantle cell lymphoma, they may experience the following side effects:

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

• pneumonia
• loss of appetite
• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in the hands or feet caused by nerve damage
• nausea or vomiting
• diarrhea
• mouth ulcers
• constipation
• muscle pain, bone pain
• hair loss and abnormal hair structure
• fatigue, feeling of weakness
• fever.

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

• shingles (localized, e.g., around the eyes or widespread on the body)
• herpes virus infection
• bacterial and viral infections
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms
• fungal infections
• allergic reactions
• insulin deficiency or resistance to normal insulin levels
• fluid retention
• sleep disorders
• loss of consciousness
• altered level of consciousness, confusion
• dizziness
• rapid heartbeat, high blood pressure, sweating
• abnormal or changed vision
• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate
• high or low blood pressure
• sudden drop in blood pressure when standing up, which may lead to fainting
• shortness of breath during exercise
• cough
• hiccups
• ringing or discomfort in the ears
• gastrointestinal bleeding
• heartburn
• abdominal pain, belching
• difficulty swallowing
• infections or inflammation of the stomach or intestines
• abdominal pain
• mouth or lip inflammation, sore throat
• liver function disorders
• itching
• redness of the skin
• rash
• muscle cramps
• urinary tract infections
• bone pain
• swelling, including around the eyes and other parts of the body
• chills
• redness and pain at the injection site
• general malaise
• weight loss
• weight gain.

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

• hepatitis
• severe allergic reaction (anaphylactic reaction), which may include symptoms such as: difficulty breathing, pain or pressure in the chest, and (or) feeling of dizziness/fainting, severe itching of the skin or hives, swelling of the face, lips, tongue, and (or) throat, which can cause difficulty swallowing, collapse
• movement disorders, paralysis, tremors
• dizziness
• hearing loss, deafness
• lung disorders making breathing difficult. Some of these include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing, wheezing
• blood clots in the lungs
• jaundice (yellowing of the skin and eyes)
• stye (hordeolum), red and swollen eyelids.

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

• blood clots in small blood vessels (microangiopathic thrombosis).

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Bortezomib Eugia

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and carton after: EXP. The expiry date refers to the last day of the month stated.
Store the vial in the outer packaging to protect from light.

For intravenous injection:

Reconstituted solution: 1 mg/ml.
Do not store in the refrigerator.
The prepared solution is chemically and physically stable for 7 days if stored at 25°C in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 7 days. If the prepared solution is not used immediately, the person administering the medicine is responsible for the storage time and conditions until administration to the patient.

For subcutaneous injection:

Reconstituted solution: 2.5 mg/ml.
Do not store in the refrigerator.
The prepared solution is chemically and physically stable for 7 days if stored at 25°C in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 7 days. If the prepared solution is not used immediately, the person administering the medicine is responsible for the storage time and conditions until administration to the patient.
Bortezomib Eugia is intended for single use only. Any unused solution or waste material should be disposed of in accordance with local regulations.

6. Package contents and other information

What Bortezomib Eugia contains

• The active substance of the medicine is bortezomib. Each vial contains 3.5 mg of bortezomib (as boron acid ester with mannitol).
• The other ingredient is: mannitol.

Solution for injection:

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

What Bortezomib Eugia looks like and what the pack contains

Bortezomib Eugia is a white or off-white lyophilized powder or granular powder.
Each carton of Bortezomib Eugia, 3.5 mg, powder for solution for injection, contains a 10 ml glass vial, type I, with a gray rubber stopper and an aluminum seal and a PP cap.
Pack sizes: 1, 3, 5, 10 vials with protective plastic cover or without.

Marketing authorization holder and manufacturer/importer

Marketing authorization holder:

Eugia Pharma (Malta) Ltd.
Vault 14, level 2
Valletta Waterfront
Floriana, FRN1914
Malta
e-mail: medicalinformation@aurovitas.pl

Manufacturer/Importer:

APL Swift Services (Malta) Ltd
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Generis Farmacêutica S.A.
Rua João de Deus 19, Venda Nova
2700-487 Amadora
Portugal
Arrow Generiques
26 Avenue Tony Garnier
69007 Lyon
France

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

Belgium
Bortezomib Eugia 3.5 mg powder for solution for injection / powder for solution injectable / Pulver zur Herstellung einer Injektionslösung
France
Bortezomib Arrow 3.5 mg powder for solution injectable
Germany
Bortezomib PUREN 3.5 mg Pulver zur Herstellung einer Injektionslösung
Italy
Bortezomib Aurobindo
Netherlands
Bortezomib Eugia 3.5 mg, powder for solution for injection
Poland
Bortezomib Eugia
Portugal
Bortezomib Generis
Spain
Bortezomib Aurovitas 3.5 mg polvo para solución inyectable EFG

Date of last revision of the leaflet: 08/2024

Information intended for healthcare professionals only:

1. PREPARATION OF THE SOLUTION FOR INTRAVENOUS INJECTION

Caution: Bortezomib Eugia is a cytotoxic medicine. When handling Bortezomib Eugia and preparing it for use, caution should be exercised. To avoid skin contact with the medicine, the use of gloves and other protective clothing is recommended.
WHEN HANDLING BORTEZOMIB EUGIA, IT IS ESSENTIAL TO STRICTLY FOLLOW ASEPTIC TECHNIQUE GUIDELINES, AS IT DOES NOT CONTAIN PRESERVATIVES.

• 1.1. Preparation of the 3.5 mg vial: carefully add 3.5 mlof sterile sodium chloride 9 mg/ml (0.9%) solution for injection to the vial containing Bortezomib Eugia powder, using an appropriate syringe, without removing the vial stopper. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. The prepared solution will be clear and colorless, and its final pH will be between 4 and 7. There is no need to check the pH of the solution.

• 1.2.Before administration, the solution should be visually inspected for any precipitate or discoloration. If any discoloration or precipitate is observed, the solution should be discarded. Ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3.The prepared solution is preservative-free and should be used immediately after preparation. However, it has been shown to be chemically and physically stable for 7 days if stored at 25°C in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 7 days. If the prepared solution is not used immediately, the person administering the medicine is responsible for the storage time and conditions until administration to the patient.

There is no need to protect the prepared solution from light.

2. ADMINISTRATION

• After reconstitution, the appropriate amount of the prepared solution should be drawn up according to the dose calculated based on the patient's body surface area.
• Before administration, the dose and concentration of the medicine in the syringe should be confirmed (ensure that the syringe is intended for intravenous administration).
• The solution is injected intravenously in a bolus injection lasting from 3 to 5 seconds.
• The intravenous catheter through which the medicine was administered should be flushed with a small amount of sterile sodium chloride 9 mg/ml (0.9%) solution for injection.

Bortezomib Eugia, 3.5 mg, powder for solution for injection SHOULD BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY ANY OTHER ROUTE. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL

The vial is for single use only, and any unused solution should be discarded.
Any unused medicine or waste material should be disposed of in accordance with local regulations.
Information intended for healthcare professionals only:
Only the 3.5 mg vial can be administered subcutaneously, as described below.

1. PREPARATION OF THE SOLUTION FOR SUBCUTANEOUS INJECTION

Caution: Bortezomib Eugia is a cytotoxic medicine. When handling Bortezomib Eugia and preparing it for use, caution should be exercised. To avoid skin contact with the medicine, the use of gloves and other protective clothing is recommended.
WHEN HANDLING BORTEZOMIB EUGIA, IT IS ESSENTIAL TO STRICTLY FOLLOW ASEPTIC TECHNIQUE GUIDELINES, AS IT DOES NOT CONTAIN PRESERVATIVES.

• 1.1. Preparation of the 3.5 mg vial: carefully add 1.4 mlof sterile sodium chloride 9 mg/ml (0.9%) solution for injection to the vial containing Bortezomib Eugia powder, using an appropriate syringe, without removing the vial stopper. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 2.5 mg/ml. The prepared solution will be clear and colorless, and its final pH will be between 4 and 7. There is no need to check the pH of the solution.

• 1.2.Before administration, the solution should be visually inspected for any precipitate or discoloration. If any discoloration or precipitate is observed, the solution should be discarded. Ensure that the correct dose is administered subcutaneously(2.5 mg/ml).
• 1.3.The prepared solution is preservative-free and should be used immediately after preparation. However, it has been shown to be chemically and physically stable for 7 days if stored at 25°C in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 7 days. If the prepared solution is not used immediately, the person administering the medicine is responsible for the storage time and conditions until administration to the patient.

There is no need to protect the prepared solution from light.

2. ADMINISTRATION

• After reconstitution, the appropriate amount of the prepared solution should be drawn up according to the dose calculated based on the patient's body surface area.
• Before administration, the dose and concentration of the prepared solution in the syringe should be confirmed (ensure that the syringe is intended for subcutaneous administration).
• The solution is injected subcutaneously at an angle of 45-90°.
• The prepared solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left side).
• The injection site should be rotated.
• If a local reaction occurs after subcutaneous injection of Bortezomib Eugia, it is recommended to administer the subcutaneous injection of Bortezomib Eugia at a lower concentration (1 mg/ml instead of 2.5 mg/ml) or to switch to intravenous administration.

Bortezomib Eugia, 3.5 mg, powder for solution for injection SHOULD BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY ANY OTHER ROUTE. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL

The vial is for single use only, and any unused solution should be discarded.
Any unused medicine or waste material should be disposed of in accordance with local regulations.