BORTEZOMIB 2.5 mg/ml Roztwór do wstrzykiwań

Treść ulotki

1. Bortezomib Glenmark 2.5 mg/ml injectable solution
   1. What is Bortezomib Glenmark 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. Package Contents and Other Information
   7. PREPARATION FOR INTRAVENOUS INJECTION
   8. ADMINISTRATION
   9. DISPOSAL
   10. ADMINISTRATION
   11. DISPOSAL

Bortezomib Glenmark 2.5 mg/ml injectable solution

Bortezomib

Generic medicine

Read this leaflet carefully before using this medicine as it contains important
information for you.

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

Contents of this leaflet:

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

Bortezomib Glenmark contains the active substance bortezomib, a so-called “proteasome inhibitor”. Proteasomes play an important role in controlling cell functions and growth. By interfering with their function, bortezomib can kill cancer cells.
Bortezomib Glenmark is used in the treatment of multiple myeloma (a type of malignant neoplasm of the bone marrow) in patients over 18 years of age:

• alone or together with the medicines liposomal pegylated doxorubicin or dexamethasone, for patients with worsening (progressive) disease after receiving at least one prior treatment or where blood stem cell transplantation has not been successful or is not feasible
• in association with the medicines melphalan and prednisone for patients with previously untreated disease who cannot receive high doses of chemotherapy with blood stem cell transplantation.
• in association with dexamethasone or dexamethasone together with thalidomide, for patients with previously untreated disease and before receiving high doses of chemotherapy with blood stem cell transplantation (induction treatment)

Bortezomib Glenmark is used for the treatment of mantle cell lymphoma (a type of malignant neoplasm that affects the lymph nodes) in patients 18 years of age or older in association with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients with previously untreated disease and for whom blood stem cell transplantation is not feasible.

2. What you need to know before using Bortezomib Glenmark

Do not use Bortezomib Glenmark

• if you are allergic to bortezomib, boron or any of the other ingredients of this medicine (listed in section 6).
• if you have severe lung or heart problems.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Bortezomib Glenmark if you have:

• low red blood cell or white blood cell count
• bleeding problems and/or low platelet count in the blood
• diarrhea, constipation, nausea or vomiting
• previously experienced fainting, dizziness or feeling lightheaded
• kidney problems
• moderate to severe liver problems
• previous conditions such as numbness, tingling or pain in the hands or feet (neuropathy)
• heart or blood pressure problems
• shortness of breath or cough
• convulsions
• shingles (even if localized around the eyes or spreading to the rest of the body)
• symptoms of tumor lysis syndrome such as, for example, muscle cramps, muscle weakness, confusion, vision disturbances or vision loss and shortness of breath
• memory loss, difficulty thinking, difficulty walking or vision loss. These may be signs of a serious brain infection and your doctor may recommend further tests and checks.

You will need to have regular blood tests before and during therapy with bortezomib, to
constantly monitor blood cell values.
If you have mantle cell lymphoma and are given rituximab together with this medicine you should
tell your doctor:

• if you think you have hepatitis or have had it in the past. In some cases, patients who have had hepatitis B may have a new attack of hepatitis, which can be fatal. If you have had a hepatitis B infection in the past, your doctor will need to monitor you carefully for signs and symptoms of active hepatitis B.

Read the package leaflets of all medicines you are taking in combination with bortezomib for
information about these medicines before starting treatment with bortezomib. When
this medicine is given together with the medicine thalidomide, pay particular attention to the
instructions on pregnancy testing and the pregnancy prevention program (see
“Pregnancy and breastfeeding” in this section).

Children and adolescents
This medicine should not be used in children and adolescents because it is not known how the
medicine works in these subjects.

Other medicines and Bortezomib Glenmark
Tell your doctor, pharmacist or nurse if you are taking or have recently taken or might
take any other medicines.
In particular, tell your doctor if you are using 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 or other conditions
• oral antidiabetics.

Pregnancy and breastfeeding
You should not use this medicine if you are pregnant, unless strictly necessary.
Men and women undergoing therapy with Bortezomib Glenmark must use effective methods of contraception
during and up to 3 months after treatment. If, despite these precautions, pregnancy occurs,
tell your doctor immediately.
You should not breastfeed during the intake of this medicine. Discuss with your doctor the most
appropriate time to start breastfeeding again after the end of therapy.
The medicine thalidomide causes birth defects and fetal death. When Bortezomib Glenmark is
given together with thalidomide, you must follow the pregnancy prevention program of

Driving and using machines
This medicine can cause fatigue, dizziness, fainting or blurred vision. Do not
drive cars or use machines if you experience any of these symptoms. Also, be
particularly careful even if these effects do not occur.

Bortezomib Glenmark contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially
‘sodium-free’.

3. How to use Bortezomib Glenmark

The doctor will calculate the dose of Bortezomib Glenmark in proportion to your height and weight
(body surface area). The standard initial dose of bortezomib is 1.3 mg/m of surface
area twice a week.
The doctor may change the dose and the total number of treatment cycles based on your
response to treatment, the occurrence of certain side effects and your general health
condition (e.g. liver problems).
Progressive multiple myeloma
When Bortezomib Glenmark is administered alone, you will receive 4 doses of bortezomib via
intravenous or subcutaneous route on days 1, 4, 8 and 11, followed by a “rest period” of 10 days without
treatment. This period of 21 days (3 weeks) corresponds to a treatment cycle. You may
receive up to 8 cycles (24 weeks).
You may also receive Bortezomib Glenmark together with the medications liposomal pegylated
doxorubicin or dexamethasone.
When Bortezomib Glenmark is administered together with liposomal pegylated doxorubicin, you will receive
a 21-day treatment cycle with bortezomib via intravenous or subcutaneous route and 30 mg/m of
liposomal pegylated doxorubicin will be administered on day 4 of the 21-day treatment cycle of Bortezomib
Glenmark as an intravenous infusion after the injection of Bortezomib
Glenmark. You may receive up to 8 cycles (24 weeks of treatment).
When Bortezomib Glenmark is administered together with dexamethasone you will receive a cycle of
21 days with bortezomib via intravenous or subcutaneous route and dexamethasone orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12, of the 21-day treatment cycle with
Bortezomib Glenmark. You may receive up to 8 cycles (24 weeks of treatment).

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and you are not eligible for blood stem cell
transplant, you will receive Bortezomib Glenmark together with two other medications: melphalan
and prednisone. In this case, the duration of a treatment cycle is 42 days (6 weeks). You will receive
9 cycles (54 weeks).

• In cycles 1 to 4, Bortezomib Glenmark is administered twice a week on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5 to 9, Bortezomib Glenmark is administered once a week on days 1, 8, 22 and 29.

Melphalan (9 mg/m ) and prednisone (60 mg/m ) are administered orally on days 1, 2, 3 and 4 of the
first week of each cycle.
If you have never been treated before for multiple myeloma and you areeligible for blood stem cell
transplant, you will receive Bortezomib Glenmark via intravenous or subcutaneous route together with
the medications: dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When Bortezomib Glenmark is administered together with dexamethasone, you will receive a cycle of
21 days with bortezomib via intravenous or subcutaneous route and dexamethasone 40 mg for
oral administration on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day treatment cycle of Bortezomib
Glenmark. You will receive 4 cycles (12 weeks of treatment).
When Bortezomib Glenmark is administered together with thalidomide and dexamethasone, the duration of
the treatment cycle is 28 days (4 weeks).
Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the cycle of
28 days with Bortezomib Glenmark and thalidomide is administered daily orally at a dose of 50 mg up to day 14 of the first cycle and, if tolerated, the dose of thalidomide is increased to 100 mg on days 15-28 and may be subsequently increased up to 200 mg per
day from the second cycle onwards. You may receive up to 6 cycles (24 weeks of treatment).

Previously untreated mantle cell lymphoma
If you have never received specific treatment for mantle cell lymphoma in the past, you will receive
bortezomib via intravenous or subcutaneous route together with the medications rituximab, cyclophosphamide,
doxorubicin and prednisone.
Bortezomib Glenmark is administered via intravenous or subcutaneous route on days 1, 4, 8 and 11,
followed by a “rest” period without treatment. The duration of the treatment cycle is 21 days (3
weeks). You may receive up to 8 treatment cycles (24 weeks).
The following medications are administered on day 1 of each 21-day treatment cycle of
Bortezomib Glenmark as an intravenous infusion:

• rituximab at 375 mg/m , cyclophosphamide at 750 mg/m and doxorubicin at 50 mg/m
• prednisone is administered orally at a dose of 100 mg/m on days 1, 2, 3, 4 and 5 of the treatment cycle with Bortezomib Glenmark.

How Bortezomib Glenmark is administered
This medication is for intravenous and subcutaneous use. Bortezomib Glenmark will be administered
by a healthcare professional experienced in the use of cytotoxic medications.
The solution is injected subcutaneously. The diluted solution is injected into a vein. The injection into
the vein is rapid, over a period of time from 3 to 5 seconds. The subcutaneous injection can be performed either
on the thigh or on the abdomen.

If you take more Bortezomib Glenmark than you should
Since this medication is administered by the doctor or nurse it is unlikely that you will take more than you should. In the unlikely event of an overdose, the doctor will monitor
for side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of these effects may be serious.
If you are given this medicine for multiple myeloma or mantle cell lymphoma, tell your
doctor immediately if you notice any of the following symptoms:

• muscle cramps, muscle weakness
• confusion, vision disturbances or vision loss, blindness, convulsions, headache
• shortness of breath, swelling of the feet or changes in heartbeat, high blood pressure, fatigue, fainting
• cough and difficulty breathing or a feeling of tightness in the chest.

Treatment with bortezomib may very commonly cause a decrease in the number of
red blood cells and white blood cells and platelets in the blood. Therefore, you will need to have regular
blood tests before and during treatment with bortezomib, to regularly check the blood cell count. You may
experience a reduction in the number of:

• platelets, which may make you more prone to bruising or bleeding without obvious injury (for example
  bleeding of the intestine, stomach, mouth and gums or cerebral or liver hemorrhage)
• red blood cells, which can cause anemia, with symptoms such as fatigue and paleness
• white blood cells, which may make you more susceptible to infections or flu-like symptoms.

If you are given Bortezomib Glenmark for the treatment of multiple myeloma, the side
effects that may occur are listed below:

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

• Sensitization, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to
  nerve damage.
• Reduction in the number of red blood cells and/or white blood cells (see above).
• Fever.
• Feeling sick (nausea) or vomiting, loss of appetite.
• Constipation with or without excessive intestinal gas (may be severe).
• Diarrhoea: if it happens it is important that you drink more water than usual. Your doctor may prescribe you
  medicines to control the diarrhoea.
• Fatigue, feeling of weakness.
• Muscle pain, bone pain.

Common side effects (may affect up to 1 in 10 people)

• Low blood pressure, sudden drop in blood pressure when standing up which can lead to fainting.
• Increased blood pressure.
• Reduced kidney function.
• Headache.
• Feeling generally unwell, pain, dizziness, feeling lightheaded, feeling weak or loss of consciousness.
• Chills.
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, cough with phlegm, flu-like
  illness.
• Herpes zoster infection (localized, including around the eyes, or widespread on the body).
• Chest pain or difficulty breathing during activity.
• Different types of skin rash.
• Itchy skin, skin nodules or dry skin.
• Flushing of the face or small broken blood vessels.
• Redness of the skin.
• Dehydration.
• Heartburn, bloating, burping, presence of gas, stomach pain, bleeding of the intestine or stomach.
• Impaired liver function.
• Irritation of the mouth or lips, dry mouth, mouth ulcers or sore throat.
• Weight loss, loss of taste.
• Muscle cramps, muscle spasms, muscle weakness, pain in arms and legs.
• Blurred vision.
• Infection of the outermost layer of the eyes and the inner surface of the eyelids (conjunctivitis).
• Nosebleeds.
• Changes or problems with sleep, sweating, anxiety, mood changes, depressed mood, restlessness or agitation,
  changes in mental state, disorientation.
• Swelling of the body, including swelling around the eyes and in other parts of the body.

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

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• Kidney failure.
• Inflammation of a vein, blood clots in the veins and lungs.
• Problems with blood clotting.
• Circulatory failure.
• Inflammation of the membrane surrounding the heart or presence of fluid around the heart.
• Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis.
• Blood in the stool, or bleeding of the mucous membranes for example mouth, vagina.
• Cerebrovascular disorders.
• Paralysis, convulsions, falls, movement disorders, abnormal sensation, altered or reduced (feeling, hearing,
  tasting, smelling), attention disorder, tremor, spasms.
• Arthritis, including inflammation of the joints of the fingers and toes and jaw.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty
  breathing, shortness of breath, shallow breathing, breathing that becomes superficial, difficult or stops, wheezing.
• Hiccups, speech disorders.
• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in the
  urine, fluid retention.
• Altered levels of consciousness, confusion, memory impairment or loss.
• Hypersensitivity.
• Hearing loss, deafness or ringing in the ears, ear discomfort.
• Hormonal changes that can affect the reabsorption of salts and water.
• Hyperactivity of the thyroid gland.
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, swelling of the eyelid
  (chalazion), red and swollen eyelids, eye discharge, vision disorders, bleeding of the eyes.
• Swollen lymph nodes.
• Joint or muscle stiffness, feeling of heaviness, groin pain.
• Hair loss or abnormal hair texture.
• Allergic reactions.
• Redness or pain at the injection site.
• Mouth pain
• Infection or inflammation of the mouth, ulcers of the mouth, esophagus, stomach and intestines sometimes
  associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or esophageal
  discomfort, difficulty swallowing, vomiting blood.
• Skin infections.
• Bacterial and viral infections.
• Dental infection.
• Inflammation of the pancreas, blockage of the bile ducts.
• Genital pain, problems with erection.
• Weight gain.
• Feeling thirsty.
• Hepatitis.
• Disorders at the injection site or at the injection device site.
• Skin reactions or disorders (which can be severe and life-threatening), skin ulcerations.
• Bruises, falls and injuries.
• Inflammation or bleeding of blood vessels that can manifest with small red or purple spots (usually on the legs)
  that can become like large bruises on the skin or tissues.
• Benign cysts.
• A serious and reversible condition of the brain that includes convulsions, high blood pressure, headache, fatigue,
  confusion, blindness or other vision problems.

Rare side effects (may affect up to 1 in 1,000 people)

• Heart problems including heart attack, angina.
• Severe inflammation of the nerves, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).
• Hot flushes.
• Alteration of the color of the veins.
• Inflammation of the spinal nerve.
• Ear problems, bleeding from the ear.
• Reduced activity of the thyroid gland.
• Budd-Chiari syndrome (the clinical signs are caused by blockage of the liver veins).
• Change or abnormal bowel function.
• Cerebral bleeding.
• Yellowing of the eyes and skin (jaundice).
• Severe allergic reaction (anaphylactic shock): the signs include difficulty breathing, chest pain or tightness, and/or
  feeling dizzy/weak, severe itching of the skin or appearance of swellings on the skin, swelling of the face, lips,
  tongue and/or throat that can cause difficulty swallowing, collapse.
• Breast disorders.
• Vaginal discharge.
• Swelling of the genitals.
• Inability to tolerate alcohol consumption.
• Wasting or loss of body mass.
• Increased appetite.
• Fistulas.
• Joint effusion.
• Cysts in the membrane covering the joints (synovial cysts).
• Fractures.
• Rupture of muscle fibers leading to other complications.
• Enlarged liver, liver hemorrhage.
• Kidney tumor.
• Skin condition similar to psoriasis.
• Skin tumor.
• Paleness of the skin.
• Increase in platelets or plasma cells (a type of white blood cells) in the blood.
• Blood clot in small blood vessels (thrombotic microangiopathy).
• Abnormal reaction to blood transfusion.
• Partial or total loss of vision.
• Decreased libido.
• Loss of saliva.
• Protrusion of the eyeballs.
• Sensitivity to light.
• Rapid breathing.
• Rectal pain.
• Gallstones.
• Hernia.
• Injuries.
• Brittle or weak nails.
• Abnormal deposition of proteins in vital organs.
• Coma.
• Intestinal ulcers.
• Damage to multiple organs.
• Death.

If you are given Bortezomib Glenmark together with other medicines for the treatment of

mantle cell lymphoma, the side effects that may occur are listed below:

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

• Pneumonia.
• Loss of appetite.
• Sensitization, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to
  nerve damage.
• Nausea and vomiting.
• Diarrhoea.
• Mouth ulcers.
• Intestinal constipation.
• Muscle pain, bone pain.
• Hair loss or abnormal hair texture.
• Fatigue, feeling of weakness.
• Fever.

Common side effects (may affect up to 1 in 10 people)

• Herpes zoster infection (localized, including around the eyes or widespread on the body).
• Herpes virus infection.
• Bacterial and viral infections.
• Respiratory infections, bronchitis, cough with phlegm, flu-like illness.
• Fungal infections.
• Hypersensitivity (allergic reaction).
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Fluid retention.
• Difficulty or problems sleeping.
• Loss of consciousness.
• Altered levels of consciousness, confused state.
• Dizziness.
• Increased heartbeat, high blood pressure, sweating.
• Vision disorders, blurred vision.
• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• High or low blood pressure.
• Sudden drop in blood pressure when standing up which can lead to fainting.
• Shortness of breath during activity.
• Cough.
• Hiccups.
• Ringing in the ears, ear discomfort.
• Bleeding of the intestine or stomach.
• Heartburn.
• Stomach pain, bloating.
• Difficulty swallowing.
• Infection or inflammation of the stomach and intestines.
• Stomach pain.
• Irritation of the mouth or lips, sore throat.
• Impaired liver function.
• Itchy skin.
• Redness of the skin.
• Skin rash.
• Muscle spasms.
• Urinary tract infection.
• Pain in the limbs.
• Swelling of the body, including swelling around the eyes and in other parts of the body.
• Chills.
• Redness and pain at the injection site.
• Feeling generally unwell.
• Weight loss.
• Weight gain.

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

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction) whose signs may include difficulty breathing, chest pain or
  tightness, and/or feeling dizzy/weak, severe itching of the skin or appearance of swellings on the skin, swelling of
  the face, lips, tongue and/or throat that can cause difficulty swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Vertigo.
• Hearing loss, deafness.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty
  breathing, shortness of breath, shallow breathing, breathing that becomes superficial, difficult or stops, wheezing.
• Blood clots in the lungs.
• Yellowing of the eyes and skin (jaundice).

Rare side effects (may affect up to 1 in 1,000 people)

• Blood clotting in small blood vessels (thrombotic microangiopathy).
• Severe inflammation of the nerves, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please contact
your doctor or pharmacist. You can also report adverse reactions directly through the national
reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse reactions, you can contribute to providing more information on the safety of
this medicine.

5. How to store Bortezomib Glenmark

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and the package after
EXP.
Store in a refrigerator (2°C-8°C).
Keep the vial in the outer packaging to protect the medicine from light.

After first opening/reconstitution/dilution
The chemical and physical stability during use has been demonstrated for 28 days if the medicine is
stored at 2 °C-8 °C and protected from light, for 7 days if the medicine is stored at 25 °C and
protected from light and for 24 hours if the medicine is stored at 25 °C (under normal
indoor lighting conditions) in the original vial and/or in a polypropylene syringe.
From a microbiological point of view, the product must be used immediately. If not
used immediately, it is the user's responsibility to comply with the storage conditions and times of
the medicine, which usually do not exceed 24 hours at 2-8 °C.
Regarding stability in the vial and/or syringe, the same storage time applies to the diluted and
undiluted solution.
This medicine is for single use only. Unused product and waste must be disposed of in accordance with
current local regulations.

6. Package Contents and Other Information

What Bortezomib Glenmark Contains

• The active ingredient is bortezomib. Each vial contains 1 ml or 1.4 ml of injectable solution containing 2.5 mg per ml of bortezomib (as boron mannitol ester).
• The other ingredients are mannitol (E421), sodium chloride, hydrochloric acid and water for injections.
• Intravenous use: After dilution, 1 ml of solution for intravenous injection contains 1 mg of bortezomib.
• Subcutaneous use: 1 ml of solution for subcutaneous injection contains 2.5 mg of bortezomib.

Description of Bortezomib Glenmark and Package Contents
Bortezomib Glenmark is a transparent solution, from colorless to pale yellow.
Transparent glass vial, with a rubber stopper and a red aluminum cap, with a snap-on opening containing 1 ml of solution.
Transparent glass vial, with a rubber stopper and a blue aluminum cap, with a snap-on opening containing 1.4 ml of solution.

Pack sizes
1 x 1 ml vial
1 x 1.4 ml vial
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
14078 Prague 4
Czech Republic

Manufacturer
Synoptis Industrial Sp. Z.o.o.
ul. Rabowicka 15, Swarzędz,
wielkopolskie, 62-020
Poland

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

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The following information is intended for healthcare professionals only:
Note: Bortezomib Glenmark is a cytotoxic agent. Consequently, particular care should be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
Pregnant personnel should not handle this medicine.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB.

1. PREPARATION FOR INTRAVENOUS INJECTION

• 1.1 Preparation of the 2.5 mg/1 ml vial: add 1.5 mlof sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing bortezomib.

Preparation of the 3.5 mg/1.4 ml vial: add 2.1 mlof sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing bortezomib.
The concentration of the resulting solution is 1 mg/ml. The solution will be transparent and from
colorless to light yellow with a final pH between 4 and 7. It is not necessary to check the pH of the
solution.

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or a color change. If particulate matter or a color change is present, the solution must be discarded. Ensure that the correct dose is administered intravenously (1 mg/ml).
• 1.3 Chemical and physical stability during use has been demonstrated for 28 days if the medicinal product is stored at 2 °C-8 °C and protected from light, for 7 days if the medicinal product is stored at 25 °C and protected from light, and for 24 hours if the medicinal product is stored at 25 °C (under normal indoor lighting conditions) in the original vial and/or in a polypropylene syringe.

From a microbiological point of view, the product must be used immediately. If
not used immediately, it is the user's responsibility to comply with the
storage conditions and times of the medicinal product, which usually do not exceed 24 hours at
2-8 C°.
During preparation for administration and during administration itself, it is not
necessary to protect the medicinal product from light.

2. ADMINISTRATION

• Once diluted, withdraw the appropriate amount of the diluted solution in accordance with the dose calculated based on the patient's body surface area.
• Confirm the dose and concentration in the syringe before use (check that the syringe is marked for intravenous administration).
• Inject the solution intravenously as a bolus over 3-5 seconds, via a peripheral or central intravenous catheter.
• Flush the intravenous or peripheral catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

Bortezomib Glenmark 2,5 mg/ml injectable solution
IS FOR SUBCUTANEOUS OR INTRAVENOUS USE.
Do not administer through other routes.
Intrathecal administration has resulted in deaths.

3. DISPOSAL

The vial is for single use and any remaining solution must be discarded.
Unused medicine and waste derived from this medicine must be disposed of in accordance
with local regulations in force for cytotoxic agents.

The following information is intended exclusively for doctors or healthcare professionals:
1PREPARATION FOR SUBCUTANEOUS INJECTION
Pregnant personnel should not handle this medicine.
Note: bortezomib is a cytotoxic agent. Consequently, particular
attention must be paid during handling and preparation. It is recommended to wear gloves and other
protective clothing to prevent skin contact.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, DURING THE
HANDLING OF BORTEZOMIB, ASEPTIC TECHNIQUE RULES MUST BE FOLLOWED.

• 1.1 Bortezomib Glenmark injectable solution is ready for use. The concentration of the solution is 2.5 mg/ml. The solution is transparent and from colorless to light yellow with a final pH between 4.0 and 6.5. It is not necessary to check the pH of the solution.
• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or color change. If particulate matter or color change is present, the solution must be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).
• 1.3 Chemical-physical stability during use has been demonstrated for 28 days if the medicine is stored at 2 °C-8 °C and protected from light, for 7 days if the medicine is stored at 25 °C and protected from light, and for 24 hours if the medicine is stored at 25 °C (under normal indoor lighting conditions) in the original vial and/or in a polypropylene syringe.

From a microbiological point of view, the product must be used immediately. If not
used immediately, it is the user's responsibility to comply with the storage conditions and
times of the medicine, which usually do not exceed 24 hours at 2-8 °C.

• 1.4 During preparation for administration and during administration itself, it is not necessary to protect the medicine from light.

2. ADMINISTRATION

• Withdraw the appropriate amount of solution in accordance with the dose calculated based on the patient's body surface area.
• Confirm the dose and concentration in the syringe before use (check that the syringe is marked for subcutaneous administration).
• Inject the solution subcutaneously, at an angle of 45-90°
• The solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left)
• With subsequent administrations, it is necessary to rotate the injection site.
• If local reactions occur at the injection site after subcutaneous injection of bortezomib, a lower concentration of bortezomib solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

Bortezomib Glenmark 2,5 mg/ml solution for injection
IS FOR SUBCUTANEOUS OR INTRAVENOUS USE.
Do not administer through other routes.
Intrathecal administration has caused deaths.

3. DISPOSAL

The vial is for single use and the remaining solution must be discarded.
Unused medicine and waste derived from such medicine must be disposed of in accordance
with current local regulations for cytotoxic agents.