Bortezomib Dr. Reddy's: detailed information

Package leaflet: Information for the user

Bortezomib Dr. Reddy’s 3.5 mg powder for solution for injection

Equivalent medicinal product
Please read all of this leaflet carefully before you use this medicine because 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 get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Bortezomib Dr. Reddy’s is and what it is used for

Bortezomib Dr. Reddy’s contains the active substance bortezomib, a so-called "proteasome inhibitor".
Proteasomes play an important role in controlling cell functions and cell growth. By interfering with their
function, bortezomib can kill tumour cells.
Bortezomib Dr. Reddy’s is used in the treatment of multiple myeloma (a type of cancer of the bone marrow) in patients aged over 18 years:

alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients with disease that has worsened (progressed) after receiving at least one prior therapy, or in whom autologous blood stem cell transplantation has failed or is not feasible
in combination with the medicines melphalan and prednisone, for patients with previously untreated disease who are not eligible for high-dose chemotherapy with autologous blood stem cell transplantation
in combination with dexamethasone or dexamethasone together with thalidomide, for patients with previously untreated disease, prior to receiving high-dose chemotherapy with autologous blood stem cell transplantation (induction treatment).

Bortezomib Dr. Reddy’s is used for the treatment of mantle cell lymphoma (a type of cancer affecting the
lymph nodes) in patients aged 18 years or older, in combination with the medicines rituximab, cyclophosphamide,
doxorubicin and prednisone, for patients with previously untreated disease for whom autologous blood stem cell transplantation is not feasible.

2. What you need to know before using Bortezomib Dr. Reddy’s

Do not use Bortezomib Dr. Reddy’s

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

Warnings and precautions
Please consult your doctor if you have:

low red blood cell or white blood cell counts
bleeding problems and/or low platelet count in the blood
diarrhoea, constipation, nausea, or vomiting
previous episodes of fainting, dizziness, or lightheadedness
kidney problems
moderate to severe liver problems
previous history of numbness, tingling, or pain in the hands or feet (neuropathy)
heart or blood pressure problems
shortness of breath or cough
seizures
herpes zoster (shingles), including localized around the eyes or spreading to other parts of the body
symptoms of tumour lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision disturbances, or loss of vision, and shortness of breath
memory loss, difficulty thinking, difficulty walking, or loss of vision. These may be signs of a serious brain infection, and your doctor may recommend further tests and monitoring. You will need regular blood tests before and during treatment with bortezomib to monitor your blood cell counts.

If you have mantle cell lymphoma and are receiving rituximab together with bortezomib, you must inform 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 experience reactivation of the infection, which can be fatal. If you have previously had a hepatitis B infection, your doctor will need to closely monitor you for signs and symptoms of active hepatitis B.

Carefully 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 thalidomide is used, pay special attention to the instructions regarding pregnancy testing and the pregnancy prevention programme (see “Pregnancy and breastfeeding” in this section).

Children and adolescents
Bortezomib must not be used in children and adolescents because the effect of the medicine in these populations is unknown.

Other medicines and Bortezomib Dr. Reddy’s
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are 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, and phenobarbital, used to treat epilepsy
St. John’s wort (Hypericum perforatum), used to treat depression or other conditions
oral antidiabetic medicines

Pregnancy and breastfeeding
You must not use bortezomib during pregnancy unless strictly necessary.
Men and women undergoing treatment with bortezomib must use effective contraception during treatment and for up to 3 months after treatment ends. If pregnancy occurs despite these precautions, inform your doctor immediately.
You must not breastfeed while taking bortezomib. Discuss with your doctor the most appropriate time to resume breastfeeding after treatment has ended.
The medicine thalidomide causes birth defects and fetal death. When bortezomib is administered together with thalidomide, you must follow the thalidomide pregnancy prevention programme (see the

Patient Information Leaflet for Thalidomide

Driving and Use of Machinery
Bortezomib may cause fatigue, dizziness, fainting, or blurred vision. Do not drive vehicles or operate machinery if you experience any of these symptoms. Exercise particular caution even if these symptoms do not occur.

3. How to use Bortezomib Dr. Reddy’s

Your doctor will calculate the dose of bortezomib based on your height and weight (body surface area). The usual starting dose of bortezomib is 1.3 mg/m² of body surface area twice weekly. Your doctor may adjust the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain adverse effects, and your overall health condition (e.g. liver problems).

Relapsed multiple myeloma
When bortezomib is administered alone, you will receive 4 doses of bortezomib intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day period (3 weeks) corresponds to one treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive bortezomib in combination with pegylated liposomal doxorubicin or dexamethasone.

When bortezomib is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with bortezomib administered intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal doxorubicin will be given on day 4 of the 21-day bortezomib treatment cycle as an intravenous infusion after the bortezomib injection.

You may receive up to 8 cycles (24 weeks).

When bortezomib is administered together with dexamethasone, you will receive a 21-day treatment cycle with bortezomib administered intravenously or subcutaneously, and oral dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day bortezomib treatment cycle.

You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and you are not eligible for autologous stem cell transplantation, you will receive bortezomib in combination with two other medicines: melphalan and prednisone.

In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

In cycles 1–4, bortezomib is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
In cycles 5–9, bortezomib is administered once weekly on days 1, 8, 22, and 29.

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

If you have never been treated before for multiple myeloma and you are eligible for autologous stem cell transplantation, you will receive bortezomib intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction therapy.

When bortezomib is administered together with dexamethasone, you will receive a 21-day treatment cycle with bortezomib administered intravenously or subcutaneously and oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day bortezomib treatment cycle.

You will receive 4 cycles (12 weeks).

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

Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day bortezomib treatment cycle, and thalidomide is administered daily orally at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the thalidomide dose is increased to 100 mg on days 15–28 and may subsequently be increased up to 200 mg daily starting 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 been treated before for mantle cell lymphoma, you 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 treatment. The treatment cycle duration is 21 days (3 weeks). You may receive up to 8 treatment cycles (24 weeks).

The following medicines are administered on day 1 of each 21-day bortezomib treatment cycle as intravenous infusions:

Rituximab at 375 mg/m², cyclophosphamide at 750 mg/m², and doxorubicin at 50 mg/m².

Prednisone is administered orally at a dose of 100 mg/m² on days 1, 2, 3, 4, and 5 of the bortezomib treatment cycle.

How Bortezomib Dr. Reddy’s is administered
This medicine is for intravenous or subcutaneous use. Bortezomib Dr. Reddy’s will be administered by a healthcare professional experienced in the use of cytotoxic medicines.

The powder for Bortezomib Dr. Reddy’s must be reconstituted before administration. This will be done by a healthcare professional. The resulting solution is then injected rapidly into a vein or under the skin.

The intravenous injection is rapid, taking 3 to 5 seconds. The subcutaneous injection can be administered either in the thigh or the abdomen.

If you receive more Bortezomib Dr. Reddy’s than you should
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive more than you should. In the unlikely event of an overdose, your doctor will monitor you for any adverse effects.

4. Possible side effects

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

Muscle cramps, muscle weakness
Confusion, loss of vision or visual disturbances, blindness, seizures, 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 and white blood cells and platelets in the blood. Therefore, you will need regular blood tests before and during treatment with bortezomib to monitor your blood cell counts regularly. 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 from the intestine, stomach, mouth and gums, or brain or liver haemorrhage)
Red blood cells, which may cause anaemia, with symptoms such as fatigue and paleness
White blood cells, which may increase your susceptibility to infections or flu-like symptoms.

If you are being given bortezomib 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)

Tingling, numbness, pins and needles, burning sensation of the skin, or pain in the 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 excess intestinal gas (may be severe)
Diarrhoea: if this occurs, it is important that you drink much more water than usual. Your doctor may prescribe medication to control diarrhoea
Tiredness, 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 may lead to fainting
Increased blood pressure
Reduced kidney function
Headache
Feeling of general malaise, pain, dizziness, feeling of emptiness in the head, feeling of weakness 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 disseminated throughout the body)
Chest pain or difficulty breathing during physical activity
Various types of skin rash
Itching of the skin, skin nodules or dry skin
Redness of the face or small capillary ruptures
Skin redness
Dehydration
Indigestion, bloating, belching, gas, stomach pain, intestinal or stomach bleeding
Changes in 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 outer layer of the eye and the inner surface of the eyelids (conjunctivitis)
Nosebleeds
Sleep disturbances or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation
Body swelling, including swelling around the eyes and 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 veins and lungs
Blood clotting problems
Circulatory failure
Inflammation of the membrane surrounding the heart or fluid accumulation around the heart
Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis
Blood in the stool, or bleeding from mucous membranes, for example mouth, vagina
Cerebrovascular disorders
Paralysis, seizures, fall, movement disorders, abnormal, altered or reduced sensation (feeling, hearing, tasting, smelling), attention disorders, tremor, spasms
Arthritis, including inflammation of the joints of the fingers of the hands, toes and jaw
Disorders affecting the lungs, preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow or difficult breathing or need to pause, wheezing
Hiccups, speech disorders
Increased or decreased urine production (due to kidney damage), painful urination or presence of blood/protein in the urine, fluid retention
Altered levels of consciousness, confusion, failure or loss of memory
Hypersensitivity
Hearing loss, deafness or ringing in the ears, ear discomfort
Hormonal changes that may affect the reabsorption of salts and water
Overactivity of the thyroid gland
Inability to produce enough insulin or resistance to normal insulin levels
Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid swelling (chalazion), red and swollen eyelids, eye discharge, vision disorders, eye bleeding
Enlargement of 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, mouth ulcers, ulcers of the oesophagus, stomach and intestine sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting with blood
Skin infections
Bacterial and viral infections
Dental infections
Inflammation of the pancreas, obstruction of bile ducts
Genital pain, erectile dysfunction
Weight gain
Feeling of thirst
Hepatitis
Injection site or catheter site disorders
Skin reactions or disorders (which may be severe and life-threatening), skin ulcerations
Bruising, falls and injuries
Inflammation or bleeding of blood vessels which may appear as small red or purple spots (usually on the legs) that may develop into large bruises on the skin or tissues
Benign cysts
A serious and reversible brain condition including seizures, 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
Hot flushes
Change in the colour of veins
Inflammation of the spinal nerve
Ear problems, ear bleeding
Reduced activity of the thyroid gland
Budd-Chiari syndrome (clinical signs caused by blockage of the liver veins)
Change or abnormal intestinal function
Cerebral haemorrhage
Yellowing of the eyes and skin (jaundice)
Severe allergic reaction (anaphylactic shock), signs include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat which may 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 fibres leading to further complications
Enlarged liver, liver haemorrhage
Kidney tumour
Skin condition similar to psoriasis
Skin tumour
Paleness of the skin
Increased 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
Eye protrusion
Light sensitivity of the eye
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 being given bortezomib in combination 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
Tingling, numbness, pins and needles, 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
Tiredness, feeling of weakness
Fever

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

Herpes zoster infection (localized, including around the eyes or disseminated throughout 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 insulin levels
Fluid retention
Difficulty or problems sleeping
Loss of consciousness
Altered levels of consciousness, confusion
Dizziness
Increased heart rate, 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 may lead to fainting
Shortness of breath during physical activity
Cough
Hiccups
Ringing in the ears, ear discomfort
Intestinal or stomach bleeding
Indigestion
Stomach pain, bloating
Difficulty swallowing
Infection or inflammation of the stomach and intestine
Stomach pain
Irritation of the mouth or lips, sore throat
Changes in liver function
Itching of the skin
Skin redness
Rash
Muscle spasms
Urinary tract infection
Limb pain
Body swelling, including swelling around the eyes and other parts of the body
Chills
Redness and pain at the injection site
Feeling of general malaise
Loss of body weight
Weight gain

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

Hepatitis
Severe allergic reaction (anaphylactic reaction), signs of which may include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat which may cause difficulty swallowing, collapse
Movement disorders, paralysis, contractions
Dizziness
Hearing loss, deafness
Disorders affecting the lungs, preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, breathing becoming shallow, difficult or interrupted, wheezing
Blood clots in the lungs
Yellowing of the eyes and skin (jaundice)
Eyelid swelling (chalazion), red and swollen eyelids

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

Blood clot in small blood vessels (thrombotic microangiopathy)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bortezomib Dr. Reddy’s

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and outer carton after EXP.
Do not store above 25°C. Store the vial in the outer packaging to protect the medicine from light.

After reconstitution
Do not refrigerate
Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C.
From a microbiological point of view, unless the reconstitution method excludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, it is the user's responsibility to ensure appropriate storage conditions and duration.
Bortezomib Dr. Reddy’s is for single use only. Any unused product and waste materials must be disposed of in accordance with local regulations.

6. Package contents and other information

What Bortezomib Dr. Reddy’s contains

The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol boronic ester).
The other components are mannitol (Ph. Eur.), nitrogen

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

Description of the appearance of Bortezomib Dr. Reddy’s and contents of the pack
Bortezomib Dr. Reddy’s powder for injectable solution is a white to off-white powder or tablet.
Each pack of Bortezomib Dr. Reddy’s 3.5 mg powder for injectable solution contains 1 glass vial of 10 ml with stopper and aluminium seal.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Dr. Reddy’s S.r.l.
Piazza Santa Maria Beltrade, 1
20123 Milan (MI), Italy

Manufacturers
Dr. Reddy’s Laboratories (UK) Ltd – 6 Riverview Road, Beverley, East Yorkshire, HU17 0LD, United Kingdom
betapharm Arzneimitteln GmbH, Kobelweg 95, Augsburg, 86156, Germany
S.C. RUAL LABORATORIES S.R.L., Splaiul Unirii nr.313, Building H, 1st floor, sector 3, Bucharest, 030138, Romania

This medicinal product is authorised in the European Economic Area countries under the following names
Germany: Bortezomib beta 3.5 mg Pulver zur Herstellung einer Injektionslösung
Romania: Bortezomib Dr. Reddy's 3.5 mg pulbere pentru solutie perfuzabila
United Kingdom: Bortezomib Dr. Reddy's 3.5 mg Powder For Solution For Injection
France: Bortezomib Reddy Pharma 3.5 mg poudre pour solution injectable
Italy: Bortezomib Dr. Reddy’s 3.5 mg polvere per soluzione iniettabile
Spain:
Bortezomib Dr Reddys 3.5 mg polvo para soluciόn inyectable EFG

The following information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: bortezomib is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB.
1.1 Preparation of the 3.5 mg vial: carefully add 3.5 ml of sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing bortezomib powder, using an appropriately sized syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution is 1 mg/ml. The solution will be clear and colourless, with a final pH between 4 and 7. There is no need to check the pH of the solution.
1.2 The solution should be inspected visually before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must not be used and must be discarded. Ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The reconstituted solution contains no preservatives and should be used immediately after preparation, although it is chemically and physically stable for 8 hours at 25°C in the original vial and/or in a syringe. The total storage time for the reconstituted medicinal product must not exceed 8 hours before administration. If the reconstituted solution is not used immediately, it is the responsibility of the user to ensure compliance with storage conditions and time limits.
It is not necessary to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the reconstituted solution according to 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 labeled for intravenous administration).
Administer the solution as an intravenous bolus injection over 3–5 seconds through a peripheral or central intravenous catheter.
Flush the intravenous catheter with sterile injectable 9 mg/ml (0.9%) sodium chloride solution.

Bortezomib Dr. Reddy’s 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE. Do not administer by 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 material derived from this medicine must be disposed of in accordance with
local applicable regulations.
The following information is intended for healthcare professionals only:
Only the 3.5 mg vial can be administered by subcutaneous route as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE FOLLOWED DURING THE HANDLING OF BORTEZOMIB.

1.1 Preparation of the 3.5 mg vial: carefully add 1.4 ml of sterile sodium chloride 9 mg/ml (0.9%) for injection to the vial containing bortezomib lyophilized powder, using an appropriately sized syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution is 2.5 mg/ml. The solution will be clear and colourless with a final pH between 4 and 7. There is no need to check the pH of the solution.

1.2 The solution should be inspected visually before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must not be used and must be discarded. Ensure that the correct dose is administered by the subcutaneous route (2.5 mg/ml).

1.3 The reconstituted solution is preservative-free and must be used immediately after preparation, although it is chemically and physically stable for 8 hours at 25°C in the original vial and/or in a syringe. The total storage time for the reconstituted medicinal product must not exceed 8 hours before administration. If the reconstituted solution is not used immediately, it is the responsibility of the user to ensure appropriate storage conditions and duration.
It is not necessary to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the reconstituted solution according to 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 labeled for subcutaneous administration).
Inject the solution subcutaneously at an angle of 45–90°.
The reconstituted solution is administered subcutaneously in the thighs (right or left) or abdomen (right or left).
For subsequent administrations, rotate the injection site.
If local reactions at the injection site occur after subcutaneous administration 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 Dr. Reddy’s 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE. Do not administer by other routes. Intrathecal administration has resulted in deaths.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with
local applicable regulations.