Bortezomib tzf

Package leaflet: Information for the user

Bortezomib TZF, 3.5 mg, powder for solution for injection
bortezomib
Read this leaflet carefully before using this medicine because it contains important information for you.

• 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 any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Bortezomib is and what it is used for

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

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

• as monotherapy or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone, in patients whose disease has worsened (progressed) after at least one prior therapy and for whom haematopoietic stem cell transplantation has failed or was not possible;
• in combination with melphalan and prednisone, in patients who have not been previously treated 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 been previously treated, prior to high-dose cytotoxic chemotherapy followed by haematopoietic stem cell transplantation (induction treatment).

Bortezomib is also used in the treatment of 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 been previously treated and who are not eligible for haematopoietic stem cell transplantation.

2. Information before using Bortezomib

When not to use Bortezomib

• 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, discuss with the doctor if:

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

Before starting treatment with Bortezomib and during therapy, the patient will have regular blood tests to monitor blood cell counts.
If the patient has mantle cell lymphoma and is receiving rituximab together with Bortezomib, inform the doctor:

• about suspected hepatitis virus infection or a history of such infection. In some cases, patients who previously had hepatitis B virus infection may experience reactivation of hepatitis, which could be fatal. In patients with a history of hepatitis B, the doctor will closely monitor for signs of active hepatitis.

Before starting treatment with Bortezomib, carefully read the package leaflets of all concomitantly used medicines to obtain information about them. If the patient is taking thalidomide, pregnancy must be ruled out, and effective contraception must be used (see section Pregnancy and breastfeeding).
Children and adolescents
Bortezomib should not be used in children and adolescents, as its effects in this age group are unknown.
Bortezomib and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to use, including over-the-counter medicines.
In particular, inform the 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 during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib must use effective contraception during treatment and for 3 months after treatment has ended. If pregnancy occurs despite contraception, inform the doctor immediately.
Do not breastfeed during treatment with Bortezomib. Discuss with the doctor the appropriate time to resume breastfeeding after treatment ends.
Thalidomide causes congenital malformations and fetal death. When Bortezomib is used in combination with thalidomide, patients must comply with the requirements of the "Thalidomide Pregnancy Prevention Programme" (see the thalidomide package leaflet).
Driving and operating machinery
Bortezomib may cause fatigue, dizziness, fainting, or blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Exercise caution even if symptoms are not present.

3. How to use Bortezomib

The doctor determines the appropriate dose of Bortezomib based on the patient's height and body weight (body surface area). The usual starting dose of Bortezomib is typically 1.3 mg/m² of body surface area (BSA), administered twice weekly.

The doctor may adjust the dose and the total number of treatment cycles depending on the patient's response to treatment, the occurrence of certain adverse reactions, and other medical conditions (e.g., liver function disorders).

Multiple myeloma

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

The patient may also receive Bortezomib in combination with either pegylated liposomal doxorubicin or dexamethasone.

If Bortezomib is administered together with pegylated liposomal doxorubicin, the patient will receive Bortezomib intravenously or subcutaneously during each 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered as an intravenous infusion at a dose of 30 mg/m² BSA on day 4 of the 21-day cycle, after administration of Bortezomib.

The patient may receive up to 8 cycles of treatment (24 weeks).

If Bortezomib is administered together with dexamethasone, the patient will receive Bortezomib intravenously or subcutaneously during each 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 treatment cycle.

The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If a patient with multiple myeloma has not been previously treated and does not qualify for hematopoietic stem cell transplantation, they will receive Bortezomib in combination with two other drugs: melphalan and prednisone.

In this case, each treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• Cycles 1–4: Bortezomib TZF is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• Cycles 5–9: Bortezomib TZF is administered once weekly on days 1, 8, 22, and 29.

Both melphalan (9 mg/m² BSA) and prednisone (60 mg/m² BSA) are administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If a patient has not been previously treated for multiple myeloma and qualifies for hematopoietic stem cell transplantation, they will receive Bortezomib intravenously or subcutaneously in combination with other drugs—dexamethasone or dexamethasone with thalidomide—as induction therapy.

When Bortezomib is administered with dexamethasone, the patient will receive Bortezomib 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 each 21-day Bortezomib treatment cycle.

The patient will receive 4 cycles (12 weeks).

When Bortezomib is administered together with dexamethasone and thalidomide, the treatment cycle lasts 28 days (4 weeks).

Dexamethasone at a dose of 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 28-day Bortezomib treatment cycle. Thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle. If this dose is well tolerated, it may be increased to 100 mg from days 15 to 28. Starting from the second cycle, the dose may be increased to 200 mg per day.

The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If a patient has not been previously treated for mantle cell lymphoma, they will receive Bortezomib intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without drug administration. 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 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 each Bortezomib treatment cycle.

How Bortezomib is administered

Bortezomib is intended for intravenous or subcutaneous administration.

Bortezomib will be administered by trained medical personnel experienced in handling cytotoxic drugs.

The Bortezomib powder must be reconstituted before use. The solution is prepared by trained medical personnel. The reconstituted solution is then injected either into a vein or under the skin.

Intravenous injection is rapid, lasting 3 to 5 seconds. Subcutaneous injection is administered in the thigh or abdomen.

Use of a higher than recommended dose of Bortezomib

Since this medicine is administered by a doctor or nurse, it is unlikely that an overdose will occur.

In the unlikely event of an overdose, the doctor will monitor the patient for any adverse reactions.

4. Possible adverse effects

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

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

• platelets, which may increase the tendency to bruise or bleed without apparent injury (e.g., bleeding from the intestines, stomach, mouth, or gums, or bleeding within the brain or liver);
• red blood cells, which may lead to anaemia with symptoms such as fatigue and pallor;
• white blood cells, which may increase susceptibility to infections or the occurrence of flu-like symptoms.

If the patient is receiving Bortezomib TZF for the treatment of multiple myeloma, the following adverse effects may occur:
Very common adverse effects (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;
• decreased number of red and (or) white blood cells (see above);
• fever;
• nausea or vomiting, loss of appetite;
• constipation, with or without abdominal distension (may be significantly worsened);
• diarrhoea: if it occurs, the patient should drink more fluids than usual; the doctor may recommend taking additional medications to control diarrhoea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

Common adverse 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;
• kidney function disorders;
• headache;
• general malaise, pain, peripheral dizziness, vertigo, 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 disseminated throughout the body);
• chest pain, shortness of breath during physical exercise;
• various types of skin rashes;
• skin itching, skin nodules or dry skin;
• facial flushing or capillary rupture;
• skin redness;
• dehydration;
• heartburn, bloating, belching, gas, 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;
• painful muscle cramps, muscle cramps, muscle weakness, limb pain;
• blurred vision;
• infection of the outer layer of the eyeball (cornea) and the mucous membrane lining the inner surface of the eyelids (conjunctivitis);
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, changes in mental state, disorientation;
• oedema, including around the eyes and in other parts of the body.

Uncommon adverse effects (may affect less than 1 in 100 people):

• heart failure, myocardial infarction, 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 membrane around the heart) or fluid in the pericardium;
• infections, including: urinary tract infections, influenza, herpes virus infections, ear and connective tissue infections;
• blood in stool, bleeding from mucous membranes, e.g., from the mouth, vagina;
• cerebral vascular disorders;
• paralysis, seizures, falls, movement disorders, abnormal, altered or weakened sensation (touch, hearing, taste, smell), attention disorders, tremor, muscle twitching;
• arthritis, including arthritis of fingers, toes and jaw;
• lung disorders causing breathing difficulties. 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;
• disturbances 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 normally secreted insulin;
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, eyelid nodule (sty), redness and swelling of the eyelid, eye discharge, vision disturbances, bleeding in the eyes;
• 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;
• infections or inflammation of the mouth, oesophagus, stomach and intestines, sometimes with associated pain and bleeding, weak intestinal peristalsis (including obstruction), abdominal and oesophageal 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;
• reactions and disorders 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;
• inflammation or bleeding of blood vessels presenting as small red or purple spots (usually on the legs) to large, bruise-like subcutaneous patches;
• benign cysts;
• severe reversible encephalopathy, including seizures, high blood pressure, headache, fatigue, confusion, blindness or other visual disturbances.

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

• heart diseases, including myocardial infarction, angina pectoris;
• severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome);
• sudden facial flushing;
• vein discoloration;
• spinal cord inflammation;
• ear diseases, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of hepatic veins);
• altered or abnormal intestinal function;
• intracranial haemorrhage;
• yellowing of the eyes or skin (jaundice);
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, chest pain or tightness and (or) dizziness/fainting, intense skin itching or raised skin rashes, swelling of the face, lips, tongue and (or) throat, which may cause difficulty swallowing, collapse;
• breast diseases;
• vaginal mucosal ulceration;
• genital organ oedema;
• alcohol intolerance;
• wasting or weight loss;
• increased appetite;
• fistula;
• joint effusion;
• synovial cyst (ganglion cyst);
• bone fractures;
• rhabdomyolysis leading to further complications;
• liver oedema, liver bleeding;
• kidney cancer;
• skin changes 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;
• photophobia;
• rapid breathing;
• anal pain;
• gallstones;
• hernia;
• injuries;
• brittle or weakened nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulceration;
• multi-organ failure;
• death.

If the patient is receiving Bortezomib TZF in combination with other medicines for the treatment of mantle cell lymphoma, the following adverse effects may occur:
Very common adverse effects (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 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, cough with sputum production, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• insufficient insulin production or resistance to normally secreted insulin;
• fluid retention;
• sleep disturbances;
• loss of consciousness;
• disturbances of consciousness, confusion;
• dizziness;
• rapid heartbeat, hypertension, excessive sweating;
• abnormal vision, blurred vision;
• heart failure, myocardial infarction, 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;
• stomach pain, belching;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• inflammation of the mouth or lips, sore throat;
• altered liver function;
• skin itching;
• skin redness;
• rash;
• muscle cramps;
• urinary tract infection;
• limb pain;
• oedema affecting the eyes and other body parts;
• chills;
• redness and pain at the injection site;
• general malaise;
• weight loss;
• weight gain.

Uncommon adverse 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, intense skin itching or skin blisters, swelling of the face, lips, tongue, throat, which may cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle twitching;
• peripheral dizziness;
• hearing loss, deafness;
• lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, dyspnoea at rest, shallow breathing or respiratory arrest, wheezing;
• blood clots in the lungs;
• jaundice (yellowing of the skin and eyes);
• eyelid nodule (sty), redness and swelling of the eyelid.

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

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring 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
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Bortezomib TZF

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and the outer carton after "Expiry date (EXP)".
"Lot" means batch number.
There are no special storage temperature requirements for this medicine.
Store the vial in the outer packaging to protect it from light.

Prepared solution
The prepared solution has been shown to be chemically and physically stable for 8 hours at 25°C, both in the vial and in a syringe. From a microbiological point of view, the medicine should be used immediately, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.
If the medicine is not used immediately, the responsibility for storage conditions and duration prior to use lies with the user.
Do not store in the refrigerator.
Bortezomib TZF is for single use only. Any unused portions or waste material should be disposed of in accordance with local regulations.

6. Contents of the package and other information

What Bortezomib contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (in the form of a boronic acid ester with mannitol).
• Other ingredient: mannitol (E 421).

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

What Bortezomib looks like and contents of the pack
Bortezomib powder for solution for injection is a white or almost white solidified powder or powder.
Each pack contains 1 single-use vial.

Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Tel.: (22) 811 18 14
For further information about this medicinal product, please contact the Marketing Authorisation Holder.

Information intended exclusively for medical professionals:

1. PREPARATION OF INJECTION SOLUTION FOR INTRAVENOUS ADMINISTRATION

Warning: Bortezomib is a cytotoxic medicinal product. Extreme caution must be taken when handling and preparing the medicinal product for use. To protect the skin from contact with the medicinal product, the use of gloves and protective clothing is recommended.
BORTEZOMIB TZF DOES NOT CONTAIN PRESERVATIVES; THEREFORE, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.

1.1. Preparation of the 3.5 mg vial: Carefully add 3.5 mL of sterile sodium chloride injection 9 mg/mL (0.9%) to the vial of Bortezomib medicinal product using a suitable syringe, without removing the stopper of the vial. Dissolution of the lyophilized powder takes less than 2 minutes.
The concentration of the resulting solution will be 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 presence of undissolved particles or discoloration. If any discoloration or precipitation is observed, the solution must be discarded. Ensure that the correct dose will be administered intravenously (1 mg/mL).

1.3. Prepared solution
The prepared solution has been shown to be chemically and physically stable for 8 hours at 25°C, both in the vial and in the syringe.
From a microbiological point of view, the medicinal product should be used immediately unless reconstitution has been carried out under controlled and validated aseptic conditions. If not used immediately, the user is responsible for the storage time and conditions prior to use.
Do not store in the refrigerator.
There is no need to protect the prepared solution from light.

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 medicinal product 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 sodium chloride 9 mg/mL (0.9%) solution.

BORTEZOMIB IS INDICATED FOR INTRAVENOUS OR SUBCUTANEOUS ADMINISTRATION ONLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL OF THE MEDICINAL PRODUCT

The vial is intended 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.

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

PREPARATION OF INJECTION SOLUTION FOR SUBCUTANEOUS ADMINISTRATION

Warning: Bortezomib is a cytotoxic medicinal product. Extreme caution must be taken when handling and preparing the medicinal product for use. To protect the skin from contact with the medicinal product, the use of gloves and protective clothing is recommended.
BORTEZOMIB TZF DOES NOT CONTAIN PRESERVATIVES; THEREFORE, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.

1.1. Preparation of the 3.5 mg vial: Carefully add 1.4 mL of sterile sodium chloride injection 9 mg/mL (0.9%) to the vial of Bortezomib TZF medicinal product using a suitable syringe, without removing the stopper of the vial. Dissolution of the lyophilized powder takes less than 2 minutes.
The concentration of the resulting solution will be 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 presence of undissolved particles or discoloration. If any discoloration or precipitation is observed, the solution must be discarded. Ensure that the correct dose will be administered subcutaneously (2.5 mg/mL).

1.3. Prepared solution
The prepared solution has been shown to be chemically and physically stable for 8 hours at 25°C, both in the vial and in the syringe.
From a microbiological point of view, the medicinal product should be used immediately unless reconstitution has been carried out under controlled and validated aseptic conditions. If not used immediately, the user is responsible for the storage time and conditions prior to use.
Do not store in the refrigerator.
There is no need to protect the prepared solution from light.

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 medicinal product 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 should be administered subcutaneously in the thigh (right or left) or abdomen (right or left side).
• Rotate injection sites for subsequent administrations.
• In case of local reactions following subcutaneous administration of Bortezomib, either administer a more dilute solution subcutaneously (dilution to 1 mg/mL instead of 2.5 mg/mL) or switch the route of administration to intravenous injection.

BORTEZOMIB IS INDICATED FOR INTRAVENOUS OR SUBCUTANEOUS ADMINISTRATION ONLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL OF THE MEDICINAL PRODUCT

The vial is intended 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.