Bortezomib Adamed

Patient Information Leaflet: User Information

Bortezomib Adamed, 2.5 mg, powder for solution for injection

Bortezomib

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

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

Table of Contents of the Leaflet

• 1. What is Bortezomib Adamed and what is it used for
• 2. Important information before using Bortezomib Adamed
• 3. How to use Bortezomib Adamed
• 4. Possible side effects
• 5. How to store Bortezomib Adamed
• 6. Contents of the pack and other information

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

Bortezomib Adamed contains the active substance bortezomib, which is a so-called "proteasome inhibitor". Proteasomes play an important role in controlling cell function and development. By disrupting their function, bortezomib can lead to the death of cancer cells.
Bortezomib Adamed is used to treat multiple myeloma (a type of 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 for whom hematopoietic stem cell transplantation was not successful or not possible;
• in combination with medicines: melphalan and prednisone, in patients who have not been previously treated and do not qualify for high-dose chemotherapy with hematopoietic stem cell transplantation.
• in combination with medicines: dexamethasone or dexamethasone with thalidomide in patients who have not been previously treated and qualify for high-dose chemotherapy with hematopoietic stem cell transplantation (induction treatment).

Bortezomib Adamed is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients aged 18 and over in combination with medicines: rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not been previously treated and do not qualify for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Adamed

When not to use Bortezomib Adamed

• 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

Before starting treatment with Bortezomib Adamed, the patient should discuss with their doctor if they have:

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

The patient will have blood tests before and during treatment with Bortezomib Adamed to regularly check the number of blood cells.
If the patient has mantle cell lymphoma and is also receiving a medicine containing rituximab, they should tell their doctor:

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

Before starting treatment with Bortezomib Adamed, the patient should carefully read the leaflets of all medicinal products that will be used at the same time with Bortezomib Adamed to obtain information about them. When taking thalidomide, it is especially important to rule out pregnancy and then use effective contraception (see section Pregnancy and breastfeeding).

Children and adolescents

Bortezomib Adamed should not be used in children and adolescents, as it is not known how the medicine works in children and adolescents.

Bortezomib Adamed and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they 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 used to treat epilepsy;
• St. John's Wort (Hypericum perforatum) used to treat depression and other conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding

Bortezomib Adamed should not be used during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib Adamed must use effective contraception during treatment and for 3 months after the end of treatment. If, despite the use of contraception, the patient becomes pregnant, they should immediately inform their doctor.
The patient should not breastfeed while taking Bortezomib Adamed. It is necessary to discuss with the doctor the safe timing of returning to breastfeeding after the end of treatment.
Thalidomide causes birth defects and fetal death. When using Bortezomib Adamed in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and using machines

Bortezomib Adamed may cause fatigue, dizziness, fainting, and blurred vision. If these symptoms occur, the patient should not drive or operate tools or machines; even if the symptoms do not occur, the patient should still be cautious.

3. How to use Bortezomib Adamed

The doctor will adjust the appropriate dose of Bortezomib Adamed for the patient based on their growth and body weight (body surface area). The most commonly used initial dose of Bortezomib Adamed is 1.3 mg/m² of 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, side effects, and additional diseases (e.g., liver disease).
Progressive multiple myeloma
If Bortezomib Adamed is administered as a single medicine, the patient will receive 4 doses of Bortezomib Adamed 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 Adamed in combination with medicines: pegylated liposomal doxorubicin or dexamethasone.
When Bortezomib Adamed is administered in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Adamed intravenously or subcutaneously during the 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² in an intravenous infusion after the injection of Bortezomib Adamed on day 4 of the 21-day cycle.
The patient may receive up to 8 cycles (24 weeks).
When Bortezomib Adamed is administered in combination with dexamethasone, the patient will receive Bortezomib Adamed intravenously or subcutaneously during the 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 treatment cycle with Bortezomib Adamed. 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 does notqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Adamed in combination with other medicines: 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 Adamed is administered twice a week, on days: 1, 4, 8,
• 11, 22, 25, 29, and 32.
• During cycles 5-9, Bortezomib Adamed 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.

• of the first week of each cycle.

If the patient has not been previously treated for multiple myeloma and doesqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Adamed intravenously or subcutaneously in combination with other medicines: dexamethasone or dexamethasone with thalidomide as induction treatment.
In the case where Bortezomib Adamed is administered with dexamethasone, the patient will receive Bortezomib Adamed intravenously or subcutaneously in 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 treatment cycle with Bortezomib Adamed. The patient may receive up to 4 cycles (12 weeks).
In the case where Bortezomib Adamed is administered with dexamethasone and thalidomide, the treatment cycle lasts 28 days (4 weeks). Dexamethasone will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day treatment cycle with Bortezomib Adamed, 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 from 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 Adamed intravenously in combination with medicines: rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib Adamed is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without medication. 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 treatment cycle with Bortezomib Adamed:
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 treatment cycle with Bortezomib Adamed.

How Bortezomib Adamed is administered

This medicine is administered intravenously or subcutaneously. Bortezomib Adamed will be administered by a healthcare professional with experience in the use of cytotoxic medicines.
The powder of Bortezomib Adamed must be dissolved before administration. The preparation of the medicine is carried out by a healthcare professional.
Then, the prepared solution is injected intravenously or subcutaneously. Intravenous injection is rapid and lasts from 3 to 5 seconds. Subcutaneous injection is administered into the thigh or abdomen.

Overdose of Bortezomib Adamed

Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive too much of the medicine.
If this happens exceptionally, the doctor will monitor the patient for side effects.

4. Possible side effects

Like all medicines, Bortezomib Adamed can cause side effects, although not everybody gets them.
Some of these side effects can be serious.
If the patient is receiving Bortezomib Adamed 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 change in heart rhythm, high blood pressure, fatigue, fainting;
• cough and difficulty breathing or pressure in the chest.

Treatment with Bortezomib Adamed can very often cause a decrease in the number of red and white blood cells and platelets in the patient's blood. Therefore, the patient must have regular blood tests before and during treatment with Bortezomib Adamed to regularly check the number of blood cells. The patient may experience a decrease in the number of:

• platelets, which can lead to a tendency to bruise or bleed without injury (e.g., bleeding from the gut, stomach, mouth, and gums, or bleeding in the brain or liver);
• red blood cells, which can lead to anemia, whose symptoms include fatigue and paleness;
• white blood cells, which can lead to increased susceptibility to infections or flu-like symptoms.

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

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

• hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in the hands or feet due to nerve damage;
• decrease in the number of red and (or) white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation occurring with or without bloating (symptoms may be severe);
• diarrhea: if it occurs, 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 can lead to fainting;
• high blood pressure;
• decreased kidney function;
• headache;
• general feeling of being unwell, pain, dizziness, confusion, 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 of the skin, skin nodules 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 throat ulcers, dry mouth, mouth or throat pain; oral mucositis;
• weight loss, loss of taste;
• muscle cramps, muscle weakness, bone pain;
• blurred vision;
• eye infection or inflammation of the conjunctiva;
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depressive mood, 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, feeling of 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 connective tissue infections;
• blood in the stool, bleeding from mucous membranes, e.g., from the mouth, vagina;
• brain vessel disorders;
• paralysis, seizures, falls, movement disorders, abnormal, changed, or weakened 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;
• changed level of consciousness, confusion, worsening or loss of memory;
• hypersensitivity;
• 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, eyelid cyst (hordeolum), eyelid redness and swelling, 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;
• infection or inflammation of the mouth, esophagus, stomach, and intestines, sometimes with accompanying pain and bleeding, poor intestinal motility (including intestinal obstruction), discomfort in the abdominal and esophageal area, difficulty swallowing;
• skin infection;
• bacterial and viral infections;
• tooth infection;
• pancreatitis, bile duct obstruction;
• genital pain, erectile dysfunction disorders;
• weight gain;
• thirst;
• hepatitis;
• disorders at the injection site or related to the 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 of blood vessels, manifested by small red or purple spots (usually on the legs) to large similar to bruise subcutaneous spots;
• mild cysts;
• severe reversible disorders of the brain, which include seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disorders.

Rare side effects(may affect up to 1 in 1000 people):

• heart disease, including heart attack, angina pectoris;
• flushing attacks;
• vein discoloration;
• spinal cord inflammation;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• changed or abnormal intestinal function;
• brain bleeding;
• jaundice (yellowing of the skin and eyes);
• eye cyst (hordeolum), eyelid redness and swelling;

If the patient is receiving Bortezomib Adamed in combination 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;
• hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in the hands or feet due to 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;
• hypersensitivity (allergic reaction);
• insulin deficiency or resistance to normal insulin levels;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• changed level of consciousness, confusion;
• feeling of dizziness;
• rapid heartbeat, high blood pressure, sweating;
• abnormal vision, blurred vision;
• heart failure, heart attack, chest pain, feeling of discomfort in the chest, rapid or slow heart rate;
• high or low blood pressure;
• sudden drop in blood pressure when changing body position, which can lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• gastrointestinal bleeding;
• heartburn;
• mouth or throat pain;
• abdominal pain;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth or throat ulcers, throat pain; mouth ulcers;
• liver function changes;
• itching of the skin;
• redness of the skin;
• rash;
• muscle cramps;
• muscle pain and bone pain;
• urinary tract infections;
• limb pain;
• swelling, including around the eyes and other parts of the body;
• chills;
• redness and pain at the injection site;
• general feeling of illness;
• weight loss;
• weight gain.

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

• hepatitis;
• severe allergic reaction (anaphylactic reaction), whose symptoms may include: difficulty breathing, pain or pressure in the chest, feeling of dizziness or fainting, severe itching of the skin or blisters on the skin, swelling of the face, lips, tongue, or throat, which can cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle twitching;
• 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);
• eye cyst (hordeolum), eyelid redness and swelling.

Rare side effects (may affect less than 1 in 1000 people)

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

Reporting side effects

If side effects occur, including those not listed in this leaflet, the patient should inform 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 of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products.
Al. Jerozolimskie 181 C

• 02-222 Warsaw Tel.: +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. By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Bortezomib Adamed

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 and outer packaging, after EXP.
Store the vial in the outer packaging to protect it from light.
There are no special storage temperature requirements for the medicine.
Solution after dilution
The solution shows chemical and physical stability for 8 hours at 25°C, 60% relative humidity, stored in a dark place, in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 8 hours. If the diluted solution is not administered immediately, the person administering the medicine to the patient is responsible for the time and conditions of storage before use.
Bortezomib Adamed is for single use only. Any unused solution or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Bortezomib Adamed contains

• The active substance of the medicine is bortezomib. Each vial contains 2.5 mg of bortezomib (as a mannitol boron ester).

The other ingredients are: mannitol (E 421).

• Injection solution for intravenous administration:
  After dissolution, 1 ml of the injection solution contains 1 mg of bortezomib.
  Injection solution for subcutaneous administration:
  After dissolution, 1 ml of the injection solution contains 2.5 mg of bortezomib.

Bortezomib Adamed powder for solution for injection is a white or off-white, granular powder or powder.
Bortezomib Adamed is available in a 10 ml vial made of colorless type I glass with a bromobutyl rubber stopper and a yellow flip-off cap.
Each pack contains 1 vial for single use.

Marketing authorization holder

Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów

Manufacturer:

Synthon Hispania SL
C/ Castelló no1, Pol. Las Salinas, Sant Boi de Llobregat
08830 Barcelona
Spain
Synthon, s.r.o.
Brněnská 32/čp. 597
678 01 Blansko
Czech Republic
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów

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

Poland
Bortezomib Adamed
Netherlands
Bortezomib Adamed

Date of last revision of the leaflet:

• 04.2021

Information intended for healthcare professionals only:

1. PREPARATION OF THE INJECTION SOLUTION FOR INTRAVENOUS ADMINISTRATION

Caution: Bortezomib Adamed is a cytotoxic product. When handling the medicine and preparing it for use, caution should be exercised. To protect against skin contact with the medicine, the use of gloves and other protective clothing is recommended.
AS Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINE.

• 1.1. Preparation of the 2.5 mg vial: add 2.5 ml of sterile, 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing the Bortezomib Adamed powder. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. After dissolution, the solution will be clear and colorless, with a pH 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 particulate matter or discoloration. In case of particles or discoloration, the solution should be discarded. The correct dose for intravenous administration(1 mg/ml) should be ensured.
• 1.3. The reconstituted solution is preservative-free and should be used immediately after preparation. The chemical and physical stability of the solution has been demonstrated for 8 hours at 25°C, 60% relative humidity, stored in a dark place, in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 8 hours. If the diluted solution is not administered immediately, the person administering the medicine to the patient is responsible for the time and conditions of storage before use.

2. ADMINISTRATION

• The prepared solution should be drawn up into a syringe 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 (the syringe should be labeled as for intravenous administration).
• The solution should be administered as a rapid intravenous injection (bolus) lasting from 3 to 5 seconds through a centrally or peripherally inserted intravenous catheter.
• The intravenous catheter through which the medicine was administered should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride injection solution.

Bortezomib Adamed 2.5 mg, powder for solution for injection SHOULD BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. Intrathecal administration has resulted in death.

3. DISPOSAL OF THE MEDICINE

The vial is for single use only, and any remaining solution should be discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
Information intended for healthcare professionals only:
Only the 2.5 mg vial can be used for subcutaneous administration, as described below.

1. PREPARATION OF THE INJECTION SOLUTION FOR SUBCUTANEOUS ADMINISTRATION

Caution: Bortezomib Adamed is a cytotoxic product. When handling the medicine and preparing it for use, caution should be exercised. To protect against skin contact with the medicine, the use of gloves and other protective clothing is recommended.
AS Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINE.

• 1.1. Preparation of the 2.5 mg vial: add 1.0 ml of sterile, 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing the Bortezomib Adamed powder. Dissolution of the lyophilized powder takes less than 2 minutes.

The concentration of the resulting solution will be 2.5 mg/ml. After dissolution, the solution will be clear and colorless, with a pH 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 particulate matter or discoloration. In case of particles or discoloration, the solution should be discarded. The correct dose for subcutaneous administration(2.5 mg/ml) should be ensured.
• 1.3. The reconstituted solution is preservative-free and should be used immediately after preparation. The chemical and physical stability of the solution has been demonstrated for 8 hours at 25°C, 60% relative humidity, stored in a dark place, in the original vial and (or) syringe. The total storage time of the solution in the syringe before administration should not exceed 8 hours. If the diluted solution is not administered immediately, the person administering the medicine to the patient is responsible for the time and conditions of storage before use.

2. ADMINISTRATION

• The prepared solution should be drawn up into a syringe 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 (the syringe should be labeled as for subcutaneous administration).
• The solution should be injected subcutaneously at an angle of 45-90°.
• The prepared solution is administered subcutaneously into the thigh (right or left) or abdomen (right or left side).
• The injection site should be changed for each subsequent injection.
• In case of a local reaction after subcutaneous injection of Bortezomib Adamed, it is recommended to administer the subcutaneous injection of Bortezomib Adamed at a lower concentration (dilution to 1 mg/ml instead of 2.5 mg/ml) or to change the route of administration to intravenous.

Bortezomib Adamed 2.5 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 OF THE MEDICINE

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