Package leaflet: Information for the user

Bortezomib medac, 3.5 mg, powder for solution for injection
Bortezomibum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

Keep this leaflet so that you can read it again if necessary.
If you have any further questions, please ask your doctor or pharmacist.
If you experience any side effects, including any side effects not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet contents

What Bortezomib medac is and what it is used for
What you need to know before using Bortezomib medac
How to use Bortezomib medac
Possible side effects
How to store Bortezomib medac
Contents of the pack and other information

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

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

Bortezomib medac is used to treat multiple myeloma (a cancer of the bone marrow) in patients aged at least 18 years:

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

Bortezomib medac is also used to treat mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged at least 18 years, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, in those who have not received prior therapy and who are not eligible for haematopoietic stem cell transplantation.

2. Important information before using Bortezomib medac

When not to use Bortezomib medac

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 lung or heart diseases.

Warnings and precautions
Before starting treatment with Bortezomib medac, discuss with the doctor or pharmacist
if any of the following apply to the patient:

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

The patient must have regular blood tests performed before and during treatment with Bortezomib medac to systematically monitor blood cell counts.
If the patient has mantle cell lymphoma and is receiving Bortezomib medac together with a medicine containing rituximab, inform the doctor:

if the patient suspects a hepatitis virus infection or has had it in the past. In several cases, patients who previously had hepatitis B virus (HBV) infection experienced reactivation of hepatitis, which could be fatal. If the patient has a history of HBV infection, the doctor will closely monitor for symptoms of active HBV.

Before starting treatment with Bortezomib medac, carefully read the package leaflets of all medicinal products being used during treatment to obtain information about them.
If thalidomide is being taken, pregnancy must be excluded first, and effective contraception must be used (see section Pregnancy and breastfeeding).
Children and adolescents
Bortezomib medac should not be used in children and adolescents, as its effects in this patient group are unknown.
Bortezomib medac and other medicines
Inform the doctor or pharmacist about all medicines currently or recently used, as well as any medicines the patient plans to use.
In particular, inform the treating 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 medac during pregnancy unless absolutely necessary.
Women of childbearing potential must use an effective method of contraception during treatment and for 8 months after its completion. If the patient wishes to freeze her eggs (oocytes) before starting treatment, she should discuss this with the doctor.
Men must not father children during treatment with Bortezomib medac and must use effective contraception during treatment and for up to 5 months after its completion. If the patient wishes to store sperm before starting treatment, he should consult the doctor.
Patients must not breastfeed during treatment with Bortezomib medac. The timing of safe resumption of breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes congenital malformations and fetal death. When Bortezomib medac 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 medac 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 medac

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

Multiple myeloma
If Bortezomib medac is administered as a single agent, the patient will receive 4 doses of Bortezomib medac 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 medac in combination with the following medicines: pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib medac is administered together with pegylated liposomal doxorubicin, the patient will receive Bortezomib medac intravenously or subcutaneously during the 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² body surface area as an intravenous infusion after Bortezomib medac injection on day 4 of the 21-day cycle.
The patient may receive up to 8 cycles (24 weeks).

When Bortezomib medac is administered together with dexamethasone, the patient will receive Bortezomib medac 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 Bortezomib medac 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 is not eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib medac in combination with other medicines: melphalan and prednisone.
In this case, the treatment cycle duration is 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

During cycles 1–4, Bortezomib medac is administered twice weekly on days: 1, 4, 8, 11, 22, 25, 29, and 32.
During cycles 5–9, Bortezomib medac 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 been previously treated for multiple myeloma and the patient is eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib medac intravenously or subcutaneously in combination with other medicines: dexamethasone or dexamethasone plus thalidomide as induction therapy.

When Bortezomib medac is administered with dexamethasone, the patient will receive Bortezomib medac intravenously or subcutaneously 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 the 21-day Bortezomib medac treatment cycle.
The patient may receive up to 4 cycles (12 weeks).

When Bortezomib medac is administered with dexamethasone and thalidomide, the treatment cycle duration is 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 medac 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 the dose is tolerated, it will be increased to 100 mg from 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 been previously treated for mantle cell lymphoma, the patient will receive Bortezomib medac intravenously or subcutaneously in combination with the following medicines: rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib medac is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without administration of any drugs. 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 medac 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 medac treatment cycle.

How Bortezomib medac is administered
This medicine is administered intravenously or subcutaneously. Bortezomib medac will be administered by trained medical personnel experienced in the use of cytotoxic medicines.
Bortezomib medac must be reconstituted before administration. The preparation of the medicine will be performed by trained medical personnel. The resulting solution is then injected into a vein or under the skin. Intravenous injection is rapid and lasts between 3 and 5 seconds. Subcutaneous injection is administered into the thigh or abdomen.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some of these adverse reactions may be serious.
If the patient is receiving Bortezomib medac for the treatment of multiple myeloma or mantle cell lymphoma, the doctor should be informed immediately if any of the following symptoms occur:

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

platelets, which may lead to a tendency to bruise or to bleeding not caused by injury (e.g., bleeding from the intestines, stomach, mouth, and gums, or hemorrhage in the brain or from the liver);
red blood cells, which may lead to anaemia, associated with symptoms such as fatigue and pallor;
white blood cells, which may lead to increased susceptibility to infections or symptoms resembling influenza.

If the patient is receiving Bortezomib medac for the treatment of multiple myeloma, they may experience the following adverse reactions:

Very common adverse reactions (may affect more than 1 in 10 people):

hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in hands or feet due to nerve damage;
reduction in the number of red and (or) white blood cells (see above);
fever;
nausea or vomiting, loss of appetite;
constipation, with or without abdominal distension (symptoms may be severe);
diarrhoea: if this occurs, the patient must drink more fluids than usual; the doctor may recommend taking additional medicines to control diarrhoea;
fatigue, feeling of weakness;
muscle pain, bone pain.

Common adverse reactions (may affect less than 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, influenza-like symptoms;
shingles (localized, for example, around the eyes, or disseminated throughout the body);
chest pain, shortness of breath during physical exercise;
various types of rashes;
itchy skin, skin nodules, or dry skin;
facial flushing or capillary rupture;
skin redness;
dehydration;
heartburn, bloating, burping, flatulence, abdominal pain, bleeding from the intestine or stomach;
liver function disorders;
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, changes in mental state, disorientation;
swelling, including around the eyes and in other parts of the body.

Uncommon adverse reactions (may affect less than 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;
blood coagulation disorders;
circulatory failure;
pericarditis (inflammation of the outer lining of the heart) or fluid 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 reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, sudden movements;
joint inflammation, including arthritis of fingers, toes, and jaw;
lung disorders making breathing difficult. These include: difficulty breathing, shortness of breath, dyspnoea at rest, shallow breathing, or respiratory arrest, wheezing;
hiccups, speech disorders;
increased or decreased urine output (due to kidney damage), painful urination, or blood/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, stye (hordeolum), redness and swelling of the eyelid, eye discharge, visual 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;
oral cavity pain;
infection or inflammation of the oral cavity, oesophagus, stomach, and intestines, sometimes with accompanying pain and bleeding, intestinal hypomotility (including obstruction), abdominal and oesophageal discomfort, difficulty swallowing, vomiting blood;
skin infection;
bacterial and viral infections;
dental infections;
pancreatitis, obstruction of bile ducts;
genital organ pain, erectile dysfunction;
weight gain;
thirst;
hepatitis;
reactions at the injection site or related to the use of a vascular catheter;
skin reactions and disorders (which may be severe and life-threatening), skin ulceration;
bruising, falls and injuries;
vascular inflammation or bleeding presenting as small red or purple spots (usually on legs) to large bruise-like subcutaneous spots;
benign cysts;
severe reversible posterior encephalopathy syndrome, which includes seizures, high blood pressure, headache, fatigue, confusion, blindness, or other visual disturbances.

Rare adverse reactions (may affect less than 1 in 1000 people):

heart diseases, including heart attack, angina pectoris;
flushing attacks;
vein discoloration;
myelitis (spinal cord inflammation);
ear disorders, ear bleeding;
hypothyroidism;
Budd-Chiari syndrome (clinical symptoms caused by blockage of hepatic veins);
altered or abnormal intestinal function;
brain haemorrhage;
yellowing of the eyes or skin (jaundice);
severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, pain or tightness in the chest, and (or) dizziness/fainting, severe skin itching or raised skin rashes, swelling of the face, lips, tongue, and (or) throat which may cause difficulty breathing and swallowing, collapse;
breast disorders;
vaginal ulceration;
genital swelling;
alcohol intolerance;
wasting or weight loss;
increased appetite;
fistula;
joint effusion;
synovial cyst (ganglion cyst);
bone fractures;
rhabdomyolysis (muscle fibre 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 respiratory 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 medac in combination with other medicines for the treatment of mantle cell lymphoma, they may experience the following adverse reactions:

Very common adverse reactions (may affect more than 1 in 10 people):

pneumonia;
loss of appetite;
hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in hands or feet due to nerve damage;
nausea or vomiting;
diarrhoea;
mouth ulcers;
constipation;
muscle pain, bone pain;
hair loss and abnormal hair structure;
fatigue, feeling of weakness;
fever.

Common adverse reactions (may affect less than 1 in 10 people):

shingles (localized, for example, around the eyes, or disseminated throughout the body);
herpes virus infection;
bacterial and viral infections;
respiratory tract infections, bronchitis, wet cough, influenza-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;
palpitations, 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 in the ears, ear discomfort;
bleeding from the intestine or stomach;
heartburn;
abdominal pain, burping;
difficulty swallowing;
infection or inflammation of the stomach or intestines;
abdominal pain;
inflammation of the mouth or lips, sore throat;
altered liver function;
itchy skin;
skin redness;
rash;
muscle cramps;
urinary tract infection;
limb pain;
swelling affecting the eyes and other body parts;
chills;
redness and pain at the injection site;
general feeling of illness;
weight loss;
weight gain.

Uncommon adverse reactions (may affect less than 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 skin blisters, swelling of the face, lips, tongue, throat, which may cause difficulty swallowing, collapse;
movement disorders, paralysis, muscle twitching;
dizziness;
hearing loss, deafness;
lung disorders making breathing difficult. These include: difficulty breathing, shortness of breath, dyspnoea at rest, shallow breathing, or respiratory arrest, wheezing;
blood clots in the lungs;
jaundice (yellowing of skin and eyes);
stye (hordeolum), redness and swelling of the eyelid.

Rare adverse reactions (may affect less than 1 in 1000 people):

blood clot in small blood vessels (thrombotic microangiopathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, PL-02-222 Warsaw, Tel.: +48 22 49-21-301, Fax: +48 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Bortezomib medac

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 "EXP".
Store the vial in the outer carton to protect it from light.
There are no special temperature storage requirements for this medicine.
Diluted solution
Chemical and physical stability has been demonstrated for 8 days when stored at 25°C and 60% relative humidity, or for 15 days at 5±3°C in the dark, both in the vial and in a polypropylene syringe.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the person administering the medicine is responsible for the duration and conditions of storage. Usually, this time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the preparation, dilution, etc. of the solution was carried out under controlled and validated aseptic conditions.
Bortezomib medac is for single use only. Any unused product or waste material should be disposed of in accordance with local regulations.

6. Contents of the Package and Other Information

What Bortezomib medac Contains

The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as a boronic acid ester with mannitol).
Other ingredient: 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 medac Looks Like and Contents of the Pack
Bortezomib medac for injection is a white or almost white lyophilized cake or powder.
Bortezomib medac is supplied in a glass vial closed with a rubber stopper and a blue flip-off cap.
Each pack contains 1 single-use vial.

Marketing Authorisation Holder
medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Tel.: +49 4103 8006-0
Fax: +49 4103 8006-100

Manufacturer
Synthon, s.r.o.
Brněnská 32/čp 597
678 01 Blansko
Czech Republic
Synthon Hispania, S.L.
C/ Castelló, nº1
Pol. Las Salinas, Sant Boi de Llobregat
08830 Barcelona
Spain

This medicinal product is authorised for sale in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Denmark, Finland, the Netherlands, Ireland, Germany, Norway, Sweden, Italy: Bortezomib medac
United Kingdom (Northern Ireland): Bortezomib

Information intended exclusively for healthcare professionals:

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

1.1 Vial preparation 3.5 mg: carefully add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib medac powder, using an appropriate syringe without removing the vial stopper. The lyophilized powder dissolves in less than 2 minutes.
The resulting solution will have a concentration of 1 mg/ml. After reconstitution, the solution is 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 or discolouration. If particles or discolouration are observed, the solution must be discarded. Ensure that the correct dose is administered intravenously (1 mg/ml).

1.3 The reconstituted product is preservative-free and should be used immediately. However, the chemical and physical stability of the prepared solution is maintained for up to 8 days prior to administration when stored at 25°C and 60% relative humidity, or for up to 15 days when stored at 5±3°C in the dark in the original vial and/or syringe. The total storage time of the solution in a syringe prior to administration must not exceed 24 hours at a temperature of 2°C to 8°C. If the diluted solution is not administered immediately after preparation, the person administering the product to the patient is responsible for the storage time and conditions prior to use.

2. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
Before administration, confirm the dose and concentration of the drug in the syringe (check that the syringe is labelled for intravenous administration).
Inject the solution as an intravenous bolus over 3 to 5 seconds through a centrally or peripherally placed 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.

Bortezomib medac 3.5 mg powder for solution for injection MUST BE ADMINISTERED
INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

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

Information intended exclusively for healthcare professionals:
Only the 3.5 mg vial may be used for subcutaneous administration, as described below.

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

4.1 Vial preparation 3.5 mg: carefully add 1.4 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution to the vial containing Bortezomib medac powder, using an appropriate syringe without removing the vial stopper. The lyophilized powder dissolves in less than 2 minutes.
The resulting solution will have a concentration of 2.5 mg/ml. After reconstitution, the solution is clear and colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.

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

4.3 The reconstituted product is preservative-free and should be used immediately. However, the chemical and physical stability of the prepared solution is maintained for up to 8 days prior to administration when stored at 25°C and 60% relative humidity, or for up to 15 days when stored at 5±3°C in the dark in the original vial and/or syringe. The total storage time of the solution in a syringe prior to administration must not exceed 24 hours at a temperature of 2°C to 8°C. If the diluted solution is not administered immediately after preparation, the person administering the product to the patient is responsible for the storage time and conditions prior to use.

5. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
Before administration, confirm the dose and concentration of the drug in the syringe (check that the syringe is labelled for subcutaneous administration).
Inject the solution 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).
Injection sites should be rotated with subsequent injections.
In the event of a local reaction following subcutaneous administration of Bortezomib medac, it is recommended to administer a less concentrated subcutaneous solution of Bortezomib medac (diluted to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous administration.

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