Bortezomib glenmark

Package leaflet: Information for the user

Bortezomib Glenmark, 3.5 mg, powder for solution for injection
Please read all of 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, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you get any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

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

Bortezomib Glenmark contains the active substance called bortezomib, which is a so-called
"proteasome inhibitor". Proteasomes play an important role in controlling cell functions and their
development process. By interfering with their function, bortezomib may lead to the death of
cancer cells.
Bortezomib Glenmark is used to treat multiple myeloma (a cancer of the bone marrow) in patients
over 18 years of age:

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

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

2. Important information before using Bortezomib Glenmark

When not to use Bortezomib Glenmark:

• if the patient is allergic to bortezomib or any of the other ingredients of this medicine (listed in section 6).
• if the patient has certain severe lung or heart diseases.

Warnings and precautions
Before starting treatment with Bortezomib Glenmark, discuss with the doctor or pharmacist if the patient:

• has a low number 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 the hands or 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 tumour lysis syndrome symptoms such as muscle cramps, muscle weakness, confusion, loss or changes in vision, and shortness of breath
• has memory loss, thinking problems, difficulty walking or loss of vision. These may be symptoms of a serious brain infection and the doctor may recommend further tests and monitoring.

The doctor will recommend regular blood tests before and during treatment with Bortezomib Glenmark to monitor blood cell counts regularly.
If the patient has mantle cell lymphoma and is receiving Bortezomib Glenmark 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 some patients who have had hepatitis B virus (HBV) infection, reactivation of hepatitis may occur, which can be fatal. If the patient has ever had HBV infection, they will be closely monitored by the doctor for signs of active hepatitis.

Before starting treatment with Bortezomib Glenmark, carefully read the package leaflets of all medicinal products taken concurrently with Bortezomib Glenmark to obtain additional information. If the patient is taking thalidomide, she should check whether she is pregnant and should use effective contraception (see section Pregnancy and breast-feeding).
Children and adolescents
Bortezomib Glenmark must not be used in children and adolescents, as it is not known how this medicine works in this patient group.
Bortezomib Glenmark and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
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 breast-feeding
Do not use Bortezomib Glenmark during pregnancy unless absolutely necessary.
Women of childbearing potential must use effective contraception during treatment and for 8 months after treatment ends. Talk to the doctor if the patient wishes to freeze eggs before starting treatment.
Men must not father a child while receiving Bortezomib Glenmark and must use effective contraception during treatment and for up to 5 months after treatment ends. Talk to the doctor before starting treatment if the patient wishes to store sperm.
Patients must not breast-feed during treatment with Bortezomib Glenmark. Discuss with the doctor a safe time to resume breast-feeding after treatment ends.
Thalidomide causes birth defects and fetal death. If Bortezomib Glenmark is used in combination with thalidomide, patients must follow the requirements of the "Thalidomide Pregnancy Prevention Programme" (see the thalidomide package leaflet).
Driving and operating machinery
Bortezomib Glenmark may cause fatigue, dizziness, fainting and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Even if no symptoms are present, caution should still be exercised.

3. How to use Bortezomib Glenmark

Your doctor will adjust the appropriate dose of Bortezomib Glenmark based on the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib Glenmark is 1.3 mg/m² of body surface area 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 adverse reactions, and the patient's condition (e.g. if the patient has liver disease).

Multiple myeloma
If Bortezomib Glenmark is used as a single agent, the patient will receive 4 doses of Bortezomib Glenmark intravenously or subcutaneously on days: 1, 4, 8, and 11, followed by a 10-day treatment break.
This 21-day treatment period (3 weeks) is referred to as one treatment cycle. The patient may receive up to 8 treatment cycles (24 weeks).
The patient may also receive Bortezomib Glenmark in combination with medications containing pegylated liposomal doxorubicin or dexamethasone.

If Bortezomib Glenmark is used in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. Pegylated liposomal doxorubicin is administered at a dose of 30 mg/m² body surface area as an intravenous infusion after administration of Bortezomib Glenmark on day 4 of the 21-day Bortezomib Glenmark treatment cycle. The patient may receive up to 8 treatment cycles (24 weeks).

If Bortezomib Glenmark is used in combination with dexamethasone, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. Dexamethasone is administered orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib Glenmark treatment cycle. The patient may receive up to 8 treatment cycles (24 weeks).

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

• During cycles 1 to 4, Bortezomib Glenmark is administered twice weekly on days: 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5 to 9, Bortezomib Glenmark is administered once weekly on days: 1, 8, 22, and 29.
  Both melphalan (at a dose of 9 mg/m² body surface area) and prednisone (at a dose of 60 mg/m² body surface area) 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 is eligible for hematopoietic stem cell transplantation, they will receive Bortezomib Glenmark intravenously or subcutaneously in combination with medications containing dexamethasone or dexamethasone with thalidomide as initial treatment (induction therapy).

If Bortezomib Glenmark is used in combination with dexamethasone, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. Dexamethasone at a dose of 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Glenmark treatment cycle. The patient will receive up to 4 treatment cycles (12 weeks).

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

Previously untreated mantle cell lymphoma
If the patient has not previously been treated for mantle cell lymphoma, they will receive Bortezomib Glenmark intravenously or subcutaneously in combination with medications containing rituximab, cyclophosphamide, doxorubicin, and prednisone. Bortezomib Glenmark 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 treatment cycles (24 weeks).

The following drugs are administered as intravenous infusions on day 1 of each 21-day Bortezomib Glenmark treatment cycle:
Rituximab at a dose of 375 mg/m² body surface area, cyclophosphamide at a dose of 750 mg/m² body surface area, and doxorubicin at a dose of 50 mg/m² body surface area.
Prednisone is administered orally at a dose of 100 mg/m² body surface area on days 1, 2, 3, 4, and 5 of the Bortezomib Glenmark treatment cycle.

How Bortezomib Glenmark is administered
This medicine is administered intravenously or subcutaneously. Bortezomib Glenmark will be administered by trained medical personnel experienced in the use of cytotoxic agents.
The Bortezomib Glenmark powder must be reconstituted before administration. Preparation of the medicine for administration is carried out by trained medical personnel. The prepared solution is then either injected intravenously or subcutaneously. The medicine is injected rapidly over 3 to 5 seconds. Subcutaneous injection is administered either into the thigh or abdomen.

Use of a higher than recommended dose of Bortezomib Glenmark
Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive too high a dose. However, if this occurs exceptionally, the doctor 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 Glenmark for the treatment of multiple myeloma or mantle cell lymphoma, inform the doctor 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 pressure

Treatment with Bortezomib Glenmark may very commonly cause a reduction in the patient's blood levels of red blood cells, white blood cells, and platelets. Therefore, the doctor will order frequent blood tests before and during treatment with Bortezomib Glenmark to monitor blood cell counts regularly.
The patient may experience a decrease in:

• platelets, which may lead to bruising or bleeding not caused by injury (e.g., bleeding from the intestines, stomach, mouth, or gums, or hemorrhage in the brain or liver)
• red blood cells, which may lead to anaemia, with symptoms such as fatigue and paleness
• white blood cells, which may increase susceptibility to infections or cause flu-like symptoms

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

• hypersensitivity, numbness, tingling, or burning sensation of the skin, or 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, it is important that the patient drinks more water than usual. The doctor may recommend taking other medicines for 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
• impaired kidney function
• headache
• general malaise, pain, dizziness, lightheadedness, feeling of weakness or loss of consciousness
• chills
• infections, including pneumonia, respiratory tract infections, bronchitis, fungal infections, wet cough, flu-like symptoms
• shingles (localized, e.g., around the eyes, or disseminated throughout the body)
• chest pain, shortness of breath during physical exertion
• various types of skin rashes
• itching, skin nodules, or dry skin
• facial flushing or capillary rupture
• skin redness
• dehydration
• heartburn, bloating, belching, flatulence, abdominal pain, bleeding from the intestines 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
• inflammation of the outer layer of the eyeball or conjunctiva
• nosebleeds
• difficulty falling asleep, 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, accelerated or slowed heart rate
• kidney failure
• inflammation of veins, blood clots in veins and pulmonary veins
• 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 senses (touch, hearing, taste, smell), concentration disorders, tremor, jerky movements
• joint inflammation, including inflammation of finger, toe, and jaw joints
• lung disorders causing inadequate oxygen supply to the body. These may 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, disorientation, worsening or loss of memory
• hypersensitivity
• hearing loss, deafness, ringing or discomfort in the ears
• hormonal disorders that may affect salt and water absorption
• hyperthyroidism
• insufficient insulin production or tissue insensitivity to normal insulin concentration
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, cataracts, and redness and swelling of eyelids, eye discharge, vision disorders, 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
• infections or inflammation of the oral cavity, ulcers of the mouth, oesophagus, stomach, and intestines, sometimes with accompanying pain and bleeding, impaired intestinal peristalsis (including obstruction), abdominal and oesophageal discomfort, difficulty swallowing, vomiting blood
• skin infection
• bacterial and viral infections
• tooth infections
• pancreatitis, biliary duct obstruction
• genital organ pain, erectile dysfunction
• weight gain
• thirst
• hepatitis
• changes at the injection site or related to the use of a vascular catheter
• skin reactions and changes (which may be severe and life-threatening), skin ulceration
• bruising, falls, and injuries
• inflammatory condition or purpura from blood vessels manifesting from small red or purple spots (usually on legs) to large bruise-like subcutaneous or deep tissue patches
• benign cysts
• severe, reversible encephalopathy involving seizures, high blood pressure, headache, fatigue, disorientation, blindness, or other visual disturbances

Rare adverse reactions (may affect less than 1 in 1,000 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 haemorrhage
• yellowing of eyes and skin (jaundice)
• severe allergic reaction (anaphylactic shock) with symptoms such as difficulty breathing, chest pain or pressure, and/or dizziness/fainting, intense skin itching or skin nodules, swelling of the face, lips, tongue, and/or throat which may cause difficulty swallowing, collapse
• breast diseases
• vaginal ulceration
• genital swelling
• alcohol intolerance
• wasting or weight loss
• increased appetite
• fistula
• joint effusion
• synovial cyst (ganglion cyst)
• bone fractures
• rhabdomyolysis 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) in blood
• abnormal reaction to blood transfusion
• partial or complete loss of vision
• decreased libido
• drooling
• exophthalmos (protruding eyes)
• photophobia (light sensitivity)
• increased respiratory rate
• anal pain
• gallstones
• hernia
• cuts and scrapes
• brittle or weak nails
• abnormal protein deposition in organs
• coma
• intestinal ulceration
• multi-organ failure
• death
• microvascular thrombosis (blood clots in small blood vessels)
• severe nerve inflammation which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)

If the patient is receiving Bortezomib Glenmark in combination with other medicines for the treatment of mantle cell lymphoma, the following adverse reactions may occur:
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, or 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, e.g., around the eyes, or disseminated throughout the body)
• herpes virus infection
• bacterial and viral infections
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms
• fungal infections
• hypersensitivity (allergic reaction)
• insufficient insulin production or tissue insensitivity to normal insulin concentration
• fluid retention
• difficulty falling asleep and sleep disturbances
• loss of consciousness
• altered level of consciousness, disorientation
• dizziness
• rapid heartbeat, high blood pressure, sweating
• visual disturbances, blurred vision
• heart failure, heart attack, chest pain, discomfort in the chest, accelerated or slowed heart rate
• high or low blood pressure
• sudden drop in blood pressure upon standing, which may lead to fainting
• shortness of breath during exertion
• cough
• hiccups
• ringing in the ears, ear discomfort
• bleeding from the intestines or stomach
• heartburn
• abdominal pain, belching
• difficulty swallowing
• infection or inflammation of the stomach and intestines
• abdominal pain
• mouth or lip pain, sore throat
• liver function disorders
• skin itching
• skin redness
• rash
• muscle cramps
• urinary tract infection
• limb pain
• body swelling, including eyes and other body parts
• chills
• redness and pain at the injection site
• general malaise
• 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 pressure and/or dizziness or fainting, intense skin itching or skin nodules, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
• movement disorders, paralysis, muscle twitching
• dizziness
• hearing loss, deafness
• lung disorders causing inadequate oxygen supply to the body. These may include: difficulty breathing, shortness of breath, dyspnoea at rest, shallow breathing, or respiratory arrest, wheezing
• blood clots in pulmonary blood vessels
• yellowing of eyes and skin (jaundice)
• cataracts and redness and swelling of eyelids

Rare adverse reactions (may affect less than 1 in 1,000 people)

• microvascular thrombosis (blood clots in small blood vessels)

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Bortezomib Glenmark

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box after: Expiry
(Exp) or on the vial label following the abbreviation Exp.
The vial should be stored in the cardboard box to protect it from light.
There are no special requirements regarding the storage temperature of the medicine.
The medicine has been shown to be chemically and physically stable for 8 hours when stored at 25°C and
60% RH, provided it is protected from light, both in the vial and in a polypropylene
syringe.
From a microbiological standpoint, the prepared solution should be used immediately. If the prepared
solution is not used immediately, the person administering the medicine is responsible for the time and
conditions of storage prior to use. Usually, the solution should not be stored for more than 24
hours at a temperature of 2 to 8°C, unless the solution has been prepared under controlled and
validated aseptic conditions.
Bortezomib Glenmark 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 packaging and other information

What Bortezomib Glenmark 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 ingredient is mannitol.

Injectable solution for intravenous administration:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Injectable solution for subcutaneous administration:
After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

What Bortezomib Glenmark looks like and contents of the pack
Bortezomib Glenmark powder for solution for injection is a white or almost white solidified powder or powder.
Bortezomib Glenmark powder for solution for injection is available in a pack containing a vial with a rubber stopper and a flip-off plastic cap.
Each pack contains 1 single-use vial.

Marketing Authorisation Holder
Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
140 78 Prague 4
Czech Republic

Manufacturer
Synthon Hispania SL
C/ Castelló 1101, Pol. Las Salinas
Sant Boi de Llobregat
08830, Barcelona
Spain

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

For further information about this medicinal product and its names in the European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
Glenmark Pharmaceuticals Sp. z o.o.
Dziekonińskiego 3
00-728 Warsaw
Email: [email protected]

Information intended exclusively for healthcare professionals:

1. PREPARATION OF INJECTION SOLUTION FOR INTRAVENOUS ADMINISTRATION

Warning: Bortezomib Glenmark is a cytotoxic medicinal product. Therefore, caution must be exercised when preparing Bortezomib Glenmark for use. To protect the skin from contact with the product, gloves and other protective clothing must be worn.
ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED DURING THE PREPARATION OF BORTEZOMIB GLENMARK, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

1.1. Reconstitution of the 3.5 mg vial: carefully add 3.5 ml of sterile sodium chloride injection solution at a concentration of 9 mg/ml (0.9%) to the vial containing the Bortezomib Glenmark powder, using a syringe of appropriate size, without removing the vial stopper.
Reconstitution 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, colourless, and the final pH will range from 4 to 7. Testing the pH of the solution is not required.

1.2. Before administration, the reconstituted solution should be visually inspected for the presence of particulate matter or discoloration. If discoloration or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered intravenously (1 mg/ml).

1.3. The reconstituted solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability of the reconstituted solution has been demonstrated for up to 8 hours when stored at 25°C in the original vial and/or syringe. The total storage time of the reconstituted solution prior to administration must not exceed 8 hours. If the reconstituted solution is not used immediately, responsibility for its storage conditions and duration prior to administration lies with the person administering the product. It is not necessary to protect the reconstituted 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 use).
• The reconstituted solution should be administered as an intravenous bolus injection over 3 to 5 seconds via a peripheral or central catheter.
• The peripheral or central catheter should be flushed with sterile sodium chloride injection solution at a concentration of 9 mg/ml (0.9%).

Bortezomib Glenmark 3.5 mg powder for solution for injection is administered SUBCUTANEOUSLY OR INTRAVENOUSLY. DO NOT ADMINISTER BY ANY OTHER ROUTE. DEATHS HAVE BEEN REPORTED AFTER INTRATHECAL ADMINISTRATION.

3. DISPOSAL OF THE MEDICINAL PRODUCT

The vial is for single use only, and any unused portion of the 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 can be administered subcutaneously, as described below.

1. PREPARATION OF THE SUBCUTANEOUS INJECTION SOLUTION

Warning: Bortezomib Glenmark is a cytotoxic medicinal product. Therefore, caution must be taken when preparing Bortezomib Glenmark for use. To protect the skin from contact with the product, gloves and other protective clothing must be worn.
ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED DURING THE PREPARATION OF BORTEZOMIB GLENMARK, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

1.1. Preparation of the 3.5 mg vial: Carefully add 1.4 ml of sterile sodium chloride solution for injection at a concentration of 9 mg/ml (0.9%) to the vial containing the lyophilized powder of Bortezomib Glenmark, using a syringe of appropriate size, without removing the vial stopper. The reconstitution of the lyophilized powder takes less than 2 minutes.
The concentration of the resulting solution will be 2.5 mg/ml. After preparation, the solution will be clear and colorless, with a final pH between 4 and 7. Checking the pH of the solution is not necessary.

1.2. Before administration, the prepared solution should be visually inspected for the presence of particulate matter or discoloration. If discoloration occurs or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).

1.3. The prepared solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability of the prepared solution has been demonstrated for up to 8 hours when stored at 25°C in the original vial and (or) syringe. The total storage time of the prepared solution before administration must not exceed 8 hours. If the prepared solution is not used immediately, responsibility for the storage time and conditions until administration to the patient lies with the person administering the product.
It is not necessary to protect the prepared solution from light.

2. ADMINISTRATION

• After reconstitution, draw up 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 whether the syringe is labeled for subcutaneous administration).
• The solution should be administered subcutaneously at an angle of 45–90°.
• The prepared solution is administered subcutaneously into the thighs (right or left) or abdomen (right or left side).
• Rotate injection sites with each subsequent administration.
• If a local reaction occurs after subcutaneous injection of Bortezomib Glenmark medicinal product, it is recommended to administer the Bortezomib Glenmark solution subcutaneously at a lower concentration (dilution to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous injection.

Bortezomib Glenmark product, 3.5 mg, powder for solution for injection is administered
SUBCUTANEOUSLY OR INTRAVENOUSLY. Do not use any other route of administration. Fatalities have been reported after
intrathecal administration.

3. DISPOSAL OF THE MEDICINAL PRODUCT

The vial is intended for single use only, and any unused portion of the solution must be discarded.
Any unused product or waste materials must be disposed of in accordance with local regulations.