Bortezomib adamed

Bortezomib Adamed 3.5 mg, powder for solution for intravenous injection
Bortezomibum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• Consult your doctor, pharmacist, or nurse if you have any doubts.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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

Bortezomib Adamed contains an active substance called bortezomib, which is a so-called
"proteasome inhibitor". Proteasomes play an important role in controlling cell functions and their
developmental processes. By interfering with their function, bortezomib may lead to the death of
cancer cells.

Bortezomib Adamed is used in the treatment of multiple myeloma (a cancer of the bone marrow) in
patients aged over 18 years:

• as a single agent or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone, in patients whose disease has progressed after at least one prior therapy and for whom hematopoietic stem cell transplantation has failed or is not possible;
• in combination with melphalan and prednisone, in patients who have not received prior treatment and who are not eligible for high-dose cytotoxic chemotherapy followed by hematopoietic stem cell transplantation;
• in combination with dexamethasone or with dexamethasone and thalidomide, in patients who have not received prior treatment and who are eligible for high-dose cytotoxic chemotherapy followed by hematopoietic stem cell transplantation (induction treatment).

Bortezomib Adamed is also used in the treatment of mantle cell lymphoma (a type of cancer affecting
lymph nodes) in patients aged at least 18 years, in combination with rituximab, cyclophosphamide,
doxorubicin, and prednisone, in those who have not received prior treatment and who are not eligible
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 particularly severe heart or lung diseases.

Warnings and precautions
Inform your doctor if the patient:

• has low numbers of red or white blood cells;
• has bleeding disorders and/or low platelet count;
• has diarrhoea, constipation, nausea, or vomiting;
• has previously experienced fainting, dizziness, or lightheadedness;
• has kidney disease;
• has moderate to severe liver function impairment;
• has previously experienced numbness, tingling, or pain in hands and feet (symptoms of neuropathy);
• has heart disease or blood pressure problems;
• has shortness of breath or cough;
• has seizures;
• has shingles (around the eyes or widespread);
• has symptoms of tumour lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss or disturbances, and difficulty breathing;
• experiences memory loss, thinking problems, difficulty walking, or vision loss. These may be symptoms of a serious brain infection, and the doctor may recommend further tests and monitoring.

Regular blood tests must be performed in the patient before and during treatment with
Bortezomib Adamed to monitor blood cell counts.
If the patient has mantle cell lymphoma and is receiving Bortezomib Adamed together with a medicine
containing rituximab, inform the doctor:

• if the patient suspects hepatitis virus infection or has had it in the past. In some cases, patients with hepatitis B virus (HBV) infection have experienced reactivation of hepatitis, which could be fatal. If the patient has a history of HBV infection, they will be closely monitored by the doctor for signs of active HBV.

Before starting treatment with Bortezomib Adamed, carefully read the package leaflets of all
medicines being taken during treatment to obtain information about them. If thalidomide is being
used, pregnancy must be ruled out first, and effective contraception must be used (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 this group.
Other medicines and Bortezomib Adamed
Inform your doctor about all medicines currently used, recently used, or planned for use.
In particular, inform your doctor if the patient is 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 and other conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding
Do not use Bortezomib Adamed during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib Adamed must use effective contraception during treatment and for 3 months after treatment has ended. If pregnancy occurs despite these measures, inform the doctor immediately.
Women must not breastfeed during treatment with Bortezomib Adamed.
The timing of safe resumption of breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes congenital malformations and fetal death. When Bortezomib Adamed is used in combination with thalidomide, patients must comply with the requirements of the "Thalidomide Pregnancy Prevention Programme" (see thalidomide package leaflet).
Driving and operating machinery
Bortezomib Adamed may cause fatigue, dizziness, fainting, and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machines. Even if no symptoms are present, caution should still be exercised.

3. How to use Bortezomib Adamed

The treating physician will adjust the appropriate dose of Bortezomib Adamed for the patient based on the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib Adamed is 1.3 mg/m² of body surface area administered twice weekly.
The physician may modify the dose and the total number of treatment cycles depending on the patient's response to treatment, the occurrence of adverse reactions, and additional medical conditions (e.g. liver disease).

Multiple myeloma
If Bortezomib Adamed is administered as a single agent, the patient will receive 4 doses of Bortezomib Adamed intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day treatment break. This 21-day period (3 weeks) is considered one treatment cycle.
The patient may receive up to 8 cycles (24 weeks).

The patient may also receive Bortezomib Adamed in combination with the following drugs: 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 a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² as an intravenous infusion after administration 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 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 Adamed cycle.
The patient may receive up to 8 cycles (24 weeks).

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

• During cycles 1–4, Bortezomib Adamed is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5–9, Bortezomib Adamed is administered once weekly 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.

If the patient has not previously been treated for multiple myeloma and the patient is eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib Adamed intravenously in combination with dexamethasone or with dexamethasone and thalidomide as induction therapy.

When Bortezomib Adamed is administered with dexamethasone, the patient will receive Bortezomib Adamed intravenously in 21-day cycles, and dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 21-day Bortezomib Adamed treatment cycle. The patient will receive up to 4 cycles (12 weeks).

When Bortezomib Adamed is administered with dexamethasone and thalidomide, each 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 each 28-day Bortezomib Adamed treatment cycle, and thalidomide will be administered orally once daily at a dose of 50 mg up to day 14 of the first cycle; if this dose is tolerated, it will be increased to 100 mg on days 15–28, and may subsequently be increased to 200 mg daily starting from the second cycle.
The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If the patient has not previously been treated for mantle cell lymphoma, the patient will receive Bortezomib Adamed intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone. Bortezomib Adamed is administered intravenously on days 1, 4, 8, and 11, followed by a "rest period" without any medication. Each treatment cycle lasts 21 days (3 weeks). The patient will receive up to 8 cycles (24 weeks).

The following drugs are administered as intravenous infusions on day 1 of each 21-day Bortezomib Adamed 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 Adamed cycle.

How Bortezomib Adamed is administered
This medicine is administered exclusively by intravenous or subcutaneous route. Bortezomib Adamed will be administered by trained medical personnel experienced in the use of cytotoxic agents.

The Bortezomib Adamed powder must be reconstituted before administration. The preparation is performed by trained medical personnel. The resulting solution is then administered either as a rapid intravenous injection over 3 to 5 seconds or subcutaneously. Subcutaneous injection is given in the thigh or abdomen.

Administration of a higher than recommended dose of Bortezomib Adamed
Since this medicine is administered by a physician or nurse, it is highly unlikely that the patient will receive an overdose.
However, if this should exceptionally occur, the physician will monitor the patient for any adverse reactions.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Some of these side effects may be serious.
If the patient is receiving Bortezomib Adamed for the treatment of multiple myeloma or mantle cell lymphoma, the doctor should be informed immediately if the patient experiences any of the following symptoms:

• muscle cramps, muscle weakness;
• confusion, loss or disturbances 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 chest tightness.

Treatment with Bortezomib Adamed may very commonly lead to a decrease in the number of red and white blood cells and platelets in the patient's blood. Therefore, blood tests must be performed frequently before and during treatment with Bortezomib Adamed to regularly monitor blood cell counts. The patient may experience a reduction in:

• platelets, which may result in a tendency to bruise or bleed without injury (e.g. bleeding from the intestines, stomach, mouth and gums, or hemorrhage in the brain or liver);
• red blood cells, which may lead to anemia accompanied by symptoms such as fatigue and pallor;
• white blood cells, which may increase susceptibility to infections or flu-like symptoms.

If the patient is receiving Bortezomib Adamed for the treatment of multiple myeloma, the following side effects may occur:
Very common side effects (may affect more than 1 in 10 people):

• hypersensitivity, numbness, tingling or burning sensations of the skin, pain in hands or feet
  caused by nerve damage;
• decreased number of red and/or white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation with or without bloating (symptoms may be severe);
• diarrhea: if it occurs, the patient should drink more fluids than usual; 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 upon standing, which may lead to fainting;
• high blood pressure;
• reduced kidney function;
• headache;
• general feeling of being unwell, pain, dizziness, lightheadedness, feeling of weakness or loss of consciousness;
• chills;
• infections including: pneumonia, respiratory tract infections, bronchitis, fungal infections, cough with sputum, flu-like symptoms;
• shingles (localized, e.g. around the eyes, or disseminated throughout the body);
• chest pain, shortness of breath during physical exercise;
• various types of skin rashes;
• itchy skin, skin nodules or dry skin;
• facial flushing or capillary rupture;
• skin redness;
• dehydration;
• heartburn, bloating, belching, flatulence, abdominal pain, bleeding from the intestine or stomach;
• liver function abnormalities;
• inflammation of the mouth or lips, dry mouth, mouth ulcers or sore throat;
• weight loss, loss of taste;
• muscle cramps, muscle weakness, limb pain;
• blurred vision;
• conjunctivitis;
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, mental status changes, disorientation;
• swelling, particularly around the eyes and other body parts.

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;
• phlebitis, blood clots in veins and lungs;
• coagulation disorders;
• circulatory failure;
• pericarditis (inflammation of the outer lining of the heart) or fluid accumulation in the pericardium;
• infections including: urinary tract infections, influenza, herpes, ear infection, connective tissue infection;
• blood in stool, bleeding from mucous membranes, e.g. from the mouth, vagina;
• cerebral vascular disorders;
• paralysis, seizures, falls, movement disorders, abnormal, altered or diminished sensation (touch, hearing, taste, smell), attention disturbances, tremor, twitching;
• joint inflammation, including inflammation of joints in fingers, toes and jaw;
• lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or respiratory arrest,
• wheezing;
• hiccups, speech disorders;
• increased or decreased urine production (due to kidney damage), painful urination, blood or protein in urine, fluid retention;
• altered level of consciousness, confusion, worsening or loss of memory;
• hypersensitivity;
• hearing loss, deafness, ringing or discomfort in the ears;
• hormonal disorders affecting salt and water absorption;
• hyperthyroidism;
• insufficient insulin production or resistance to normal insulin levels;
• eye irritation or inflammation, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid nodule (sty), redness and swelling of the eyelid, eye discharge, vision disturbances, eye bleeding;
• enlarged lymph nodes;
• joint 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 associated pain and bleeding, impaired intestinal peristalsis (including bowel obstruction),
• abdominal or esophageal discomfort, difficulty swallowing, vomiting blood;
• skin infection;
• bacterial and viral infections;
• dental infections;
• pancreatitis, biliary duct obstruction;
• genital organ pain, erectile dysfunction;
• weight gain;
• thirst;
• hepatitis;
• injection site reactions or complications related to vascular catheter use;
• skin reactions and disorders (which may be severe and life-threatening), skin ulceration;
• bruising, falls and injuries;
• inflammation or bleeding from blood vessels manifesting as small red or purple spots (usually on legs) to large bruise-like subcutaneous patches;
• benign cysts;
• severe reversible posterior leukoencephalopathy syndrome (RPLS), which includes seizures, high blood pressure, headache, fatigue, confusion, blindness or other visual disturbances.

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

• heart diseases including heart attack, angina;
• flushing attacks;
• vein discoloration;
• spinal cord inflammation;
• ear diseases, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by obstruction of hepatic veins);
• altered or abnormal intestinal function;
• brain hemorrhage;
• yellowing of eyes or skin (jaundice);
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, chest pain or tightness, and/or dizziness/fainting, severe skin itching or skin hives, swelling of face, lips, tongue and/or throat which may cause difficulty breathing and swallowing, collapse;
• breast diseases;
• vaginal ulceration;
• genital swelling;
• alcohol intolerance;
• wasting or weight loss;
• increased appetite;
• fistula;
• joint effusion;
• cyst in joint lining (synovial cyst);
• bone fractures;
• rhabdomyolysis (muscle fiber breakdown) leading to further complications;
• liver swelling, liver bleeding;
• kidney cancer;
• skin condition resembling psoriasis;
• skin cancer;
• skin pallor;
• increased number of platelets or plasma cells (a type of white blood cell);
• blood clot in small blood vessels (thrombotic microangiopathy);
• abnormal reaction to blood transfusion;
• partial or complete vision loss;
• decreased libido;
• drooling;
• exophthalmos (protruding eyes);
• photophobia (light sensitivity);
• increased breathing rate;
• anal pain;
• gallstones;
• hernia;
• cuts;
• brittle or weak nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulceration;
• multi-organ failure;
• death;
• severe nerve inflammation which may lead to paralysis and breathing difficulties (Guillain-Barré syndrome).

If the patient is receiving Bortezomib Adamed in combination with other medicines for the treatment of mantle cell lymphoma, the following side effects may occur:
Very common side effects (may affect more than 1 in 10 people):

• pneumonia;
• loss of appetite;
• hypersensitivity, numbness, tingling or burning sensations of the skin, pain in hands or feet due to nerve damage;
• nausea or vomiting;
• diarrhea;
• mouth ulcers;
• constipation;
• muscle pain, bone pain;
• hair loss and abnormal hair 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 disseminated throughout the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, productive cough, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• insufficient insulin production or resistance to normal insulin levels;
• fluid retention;
• sleep disturbances;
• loss of consciousness;
• altered level of consciousness, confusion;
• dizziness;
• rapid heartbeat, high blood pressure, sweating;
• visual disturbances, blurred 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 upon changing position which may lead to fainting;
• shortness of breath during exertion;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• bleeding from the intestine or stomach;
• heartburn;
• mouth pain, sore throat;
• abdominal pain, belching;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• inflammation of the mouth or lips, sore throat, mouth ulcers;
• altered liver function;
• skin itching;
• skin redness;
• rash;
• muscle cramps;
• muscle pain, bone pain;
• urinary tract infection;
• limb pain;
• swelling affecting eyes and other body parts;
• 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), symptoms of which may include: difficulty breathing, chest pain or tightness, dizziness or fainting, severe skin itching or blisters, swelling of face, lips, tongue, throat, which may cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle cramps, muscle twitching;
• dizziness;
• hearing loss, deafness;
• lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or respiratory arrest, wheezing;
• blood clots in the lungs;
• jaundice (yellowing of skin and eyes);
• eyelid nodule (sty), redness and swelling of the eyelid.

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

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

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, the patient should inform their doctor or pharmacist.
Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
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.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Bortezomib Adamed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and outer packaging, following "Expiry (EXP)".
Store the vial in the outer carton to protect it from light.
No special precautions regarding storage temperature are required for this medicinal product.

Reconstituted solution
Chemical and physical stability of the medicinal product has been demonstrated for 8 hours when stored in the dark at 25 °C and 60% RH, both in the vial and in a polypropylene syringe.
From a microbiological standpoint, the product should be used immediately after preparation. If not used immediately, the storage time and conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2 °C to 8 °C, unless reconstitution/dilution was carried out under controlled aseptic conditions.

Bortezomib Adamed is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

What Bortezomib Adamed contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (in the form of mannitol and boric acid ester).
• The other ingredients (excipients) are: mannitol (E 421).

Intravenous injection solution:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Subcutaneous injection solution:
After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

What Bortezomib Adamed looks like and contents of the pack
Bortezomib Adamed powder for solution for injection is a white or off-white lyophilised powder or powder.
Bortezomib Adamed is packed in a 10 ml vial made of colourless type I glass, with a bromobutyl rubber stopper, aluminium seal, and a plastic flip-off cap, placed in a cardboard box.
The pack contains 1 single-use vial.

Marketing Authorisation Holder:
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland

Manufacturer:
Synthon Hispania S.L.
Castello, 1
Poligono Las Salinas
08830 Sant Boi de Llobregat
Spain

Synthon s.r.o. Blansko
Brnenska 32/c.p.597, 678 01 Blansko
Czech Republic

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

04.2021

The following information is intended for healthcare professionals only:

1. PREPARATION OF INTRAVENOUS INJECTION SOLUTION
Warning: Bortezomib Adamed is a cytotoxic product. Care must be taken when handling and preparing the medicine. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINE.

1.1. Reconstitution of the 3.5 mg vial: add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib Adamed powder. The lyophilised powder dissolves in less than 2 minutes.
The resulting solution will have a concentration of 1 mg/ml. After reconstitution, the solution will be clear and colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.

1.2. Before administration, visually inspect the solution for particles and discolouration. If particles or discolouration are observed, the solution must be discarded. Check the concentration on the vial label to ensure the correct intravenous dose (1 mg/ml) is administered.

1.3. The reconstituted solution contains no preservatives and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 8 hours prior to administration when stored at 25°C in the original vial and/or syringe. The total storage time of the solution in the syringe before administration must not exceed 8 hours. If the reconstituted solution is not administered immediately after preparation, the person administering the medicine is responsible for the time and storage conditions prior to use.
There is no need to protect the reconstituted solution from light.

2. ADMINISTRATION

• After dissolution, withdraw the appropriate volume of reconstituted solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (check that the syringe is labelled for intravenous administration).
• Administer the solution as an intravenous bolus injection over 3 to 5 seconds via a centrally or peripherally inserted intravenous catheter.
• The intravenous catheter used for administration should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride injection solution after administration.

3. DISPOSAL OF MEDICINE
The vial is for single use only, and any unused solution must be discarded.
Any unused product or waste material must be disposed of in accordance with local regulations.

The following information is intended for healthcare professionals only: Only the 3.5 mg vial may be used for subcutaneous administration as described below.

1. PREPARATION OF SUBCUTANEOUS INJECTION SOLUTION
Warning: Bortezomib Adamed is a cytotoxic product. Care must be taken when handling and preparing the medicine. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINE.

1.1. Reconstitution of the 3.5 mg vial: add 1.4 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib Adamed powder.
The lyophilised powder dissolves in less than 2 minutes.
The resulting solution will have a concentration of 2.5 mg/ml. After reconstitution, the solution will be clear and colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.

1.2. Before administration, visually inspect the solution for particles and discolouration. If particles or discolouration are observed, the solution must be discarded. Ensure that the correct subcutaneous dose (2.5 mg/ml) is administered.

1.3. The reconstituted solution contains no preservatives and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 8 hours prior to administration when stored at 25°C in the original vial and/or syringe. The total storage time of the solution in the syringe before administration must not exceed 8 hours. If the reconstituted solution is not administered immediately after preparation, the person administering the medicine is responsible for the time and storage conditions prior to use.
There is no need to protect the reconstituted solution from light.

2. ADMINISTRATION

• After dissolution, withdraw the appropriate volume of reconstituted solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and concentration of the medicine in the syringe (check that the syringe is labelled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The reconstituted solution is administered subcutaneously into the thigh (right or left) or abdomen (right or left side).
• Injection sites should be rotated with each administration.
• In the event of local reactions after subcutaneous administration of Bortezomib Adamed, it is recommended to administer a lower concentration subcutaneous solution (diluted to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous administration.

Bortezomib Adamed powder for solution for injection 3.5 mg
MUST BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.
3. DISPOSAL OF MEDICINE
The vial is for single use only, and any unused solution must be discarded.
Any unused product or waste material must be disposed of in accordance with local regulations.