Bortezomib Aurobindo

Package leaflet: Information for the user

Bortezomib Aurobindo 3.5 mg powder for solution for injection

Equivalent medicine
Please read all of this leaflet carefully before you start using 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

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

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

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

2. What you need to know before using Bortezomib Aurobindo

Do not use Bortezomib Aurobindo

• 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
Contact your doctor if you have any of the following conditions:

• low red blood cell or white blood cell count;
• bleeding problems and/or low platelet count in the blood;
• diarrhoea, constipation, nausea or vomiting;
• history of fainting, dizziness or feeling lightheaded;
• kidney problems;
• moderate to severe liver problems;
• previous history of numbness, tingling or pain in the hands or feet (neuropathy);
• heart problems or blood pressure issues;
• shortness of breath or cough;
• seizures;
• 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 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 examinations.

You will need regular blood tests before and during treatment with Bortezomib Aurobindo to monitor your blood cell counts continuously.
If you have mantle cell lymphoma and are receiving rituximab together with Bortezomib Aurobindo, you must inform your doctor:

• if you think you have hepatitis or have had it in the past. In some cases, patients who have previously had hepatitis B may experience a reactivation of the infection, which could be fatal. If you have had a previous hepatitis B infection, your doctor will need to monitor you closely for signs and symptoms of active hepatitis B.

Before starting treatment with Bortezomib Aurobindo, read the package leaflets of all other medicines you are taking in combination with Bortezomib Aurobindo for information about those medicines.
When thalidomide is used, special attention must be paid to instructions regarding pregnancy testing and pregnancy prevention requirements (see Pregnancy and breastfeeding in this section).

Children and adolescents
Bortezomib Aurobindo must not be used in children and adolescents because it is not known how the medicine affects these individuals.

Other medicines and Bortezomib Aurobindo
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 or phenobarbital, used to treat epilepsy;
• St John's wort (Hypericum perforatum), used to treat depression or other conditions;
• oral antidiabetic agents.

Pregnancy and breastfeeding
You must not use Bortezomib Aurobindo during pregnancy unless strictly necessary.
Women of childbearing age must use effective contraception during treatment and for 8 months after the end of treatment. Consult your doctor if you wish to freeze your eggs before starting treatment.
Men must not father a child during treatment with Bortezomib Aurobindo and must use an effective contraceptive method during treatment and for 5 months after the end of treatment. Consult your doctor if you wish to preserve sperm before starting treatment.
You must not breastfeed while taking Bortezomib Aurobindo. Discuss with your doctor the most appropriate time to resume breastfeeding after the end of treatment.
Thalidomide causes birth defects and fetal death. When Bortezomib Aurobindo is administered together with thalidomide, the thalidomide pregnancy prevention programme must be followed (see the thalidomide package leaflet).

Driving and using machines
Bortezomib Aurobindo may cause fatigue, dizziness, fainting or blurred vision. Do not drive or operate tools or machinery if you experience these side effects; exercise particular caution even if these symptoms do not occur.

3. How to use Bortezomib Aurobindo

Your doctor will calculate the dose of Bortezomib Aurobindo based on your height and weight (body surface area). The usual starting dose of Bortezomib Aurobindo is 1.3 mg/m² of body surface area, administered 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 side effects, and your overall health status (e.g. liver problems).

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

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

When Bortezomib Aurobindo is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib Aurobindo given intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day Bortezomib Aurobindo treatment cycle as an intravenous infusion after the Bortezomib Aurobindo injection.
You may receive up to 8 cycles (24 weeks of treatment).

When Bortezomib Aurobindo is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Aurobindo given 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 Aurobindo treatment cycle. 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 are not eligible for blood stem cell transplantation, you will receive Bortezomib Aurobindo 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 to 4, Bortezomib Aurobindo is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, Bortezomib Aurobindo 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 are eligible for blood stem cell transplantation, you will receive Bortezomib Aurobindo intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

When Bortezomib Aurobindo is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Aurobindo given intravenously and oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Aurobindo treatment cycle.
You will receive 4 cycles (12 weeks of treatment).

When Bortezomib Aurobindo is administered together with thalidomide and dexamethasone, the treatment cycle duration is 28 days (4 weeks).
Oral dexamethasone 40 mg is administered on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib Aurobindo treatment cycle, and thalidomide is administered orally daily at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the thalidomide dose will be 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 previously received specific treatment for mantle cell lymphoma, you will receive Bortezomib Aurobindo intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Aurobindo is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a treatment-free "rest" period. 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 Aurobindo 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 Aurobindo treatment cycle.

How Bortezomib Aurobindo is administered
This medicine is for intravenous or subcutaneous use. Bortezomib Aurobindo will be administered by a healthcare professional experienced in the use of cytotoxic medicines.
The Bortezomib Aurobindo powder must be reconstituted before administration. This will be done by a healthcare professional. The resulting solution is then injected into a vein or under the skin.
The intravenous injection is rapid, administered over a period of 3 to 5 seconds. The subcutaneous injection can be given in the thighs or abdomen.

If you receive more Bortezomib Aurobindo 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 side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you are being treated with Bortezomib Aurobindo for multiple myeloma or mantle cell lymphoma,
inform your doctor immediately if you notice any of the following symptoms:

• muscle cramps, muscle weakness;
• confusion, vision disturbances or loss of vision, 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 Aurobindo may very commonly cause a decrease in the number of red blood cells, white blood cells, and platelets in the blood. Therefore, you will need to have regular blood tests before and during treatment with Bortezomib Aurobindo to monitor your blood cell counts regularly. You may experience a reduction in the number of:

• platelets, which could 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 can 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 treated with Bortezomib Aurobindo for multiple myeloma, the possible side effects are listed below:
Very common side effects (may affect more than 1 in 10 people)

• tingling, numbness, pins and needles or 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 medicines to control diarrhoea;
• fatigue (tiredness), feeling weak;
• 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 which may lead to fainting;
• high blood pressure;
• reduced kidney function;
• headache;
• general feeling of discomfort, pain, dizziness, feeling faint or 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 disseminated over the body);
• chest pain or difficulty breathing during physical activity;
• various types of skin rash;
• skin itching, skin nodules or dry skin;
• facial flushing or small capillary ruptures;
• skin redness;
• dehydration;
• heartburn, bloating, burping, gas, stomach pain, intestinal or stomach bleeding;
• altered 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 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 stools or bleeding from mucous membranes, for example mouth, vagina;
• cerebrovascular disorders;
• paralysis, seizures, falls, movement disorders, abnormal, altered or reduced sensation (feeling, hearing, taste, smell), attention disorders, tremor, spasms;
• arthritis, including inflammation of the joints of the fingers, toes and jaw;
• lung disorders that prevent your body from receiving enough oxygen. These may include difficulty breathing, shortness of breath, laboured breathing even without physical activity, breathing becoming shallow, difficult or interrupted, wheezing;
• hiccups, speech disorders;
• increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in urine, fluid retention;
• altered levels of consciousness, confusion, impaired or loss of memory;
• hypersensitivity;
• hearing loss, deafness or ringing in the ears, ear discomfort;
• hormonal disturbances affecting 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, cysts in the eyes (chalazion), red and swollen eyelids, eye discharge, abnormal vision, eye bleeding;
• 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, mouth ulcers, 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;
• pancreatitis, obstruction of bile ducts;
• genital pain, erectile problems;
• weight gain;
• thirst;
• hepatitis;
• injection site or catheter site disorders;
• skin reactions or disorders (which may be severe and life-threatening), skin ulceration;
• bruises, 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;
• severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome);
• hot flushes;
• change in vein colour;
• inflammation of the spinal nerve;
• ear problems, bleeding from the ear;
• reduced activity of the thyroid gland;
• Budd-Chiari syndrome (clinical signs caused by blockage of the liver veins);
• change or abnormal intestinal function;
• brain haemorrhage;
• yellowing of the eyes and skin (jaundice);
• severe allergic reaction (anaphylactic shock), signs of which include difficulty breathing, chest pain or tightness, and/or dizziness/fainting, 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;
• genital swelling;
• 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;
• muscle fibre rupture leading to further complications;
• enlarged liver, liver haemorrhage;
• kidney tumour;
• skin condition resembling psoriasis;
• skin tumour;
• paleness of the skin;
• increased platelets or plasma cells (a type of white blood cell) in the blood;
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• loss of saliva;
• eye protrusion;
• light sensitivity;
• rapid breathing;
• rectal pain;
• gallstones;
• hernia;
• injuries;
• brittle or weak nails;
• abnormal protein deposition in vital organs;
• coma;
• intestinal ulcers;
• multi-organ damage;
• death.

If you are being treated with Bortezomib Aurobindo in combination with other medicines for mantle cell lymphoma, the possible side effects are listed below:
Very common side effects (may affect more than 1 in 10 people)

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

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

• Herpes zoster infection (localized including around the eyes or disseminated over 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 disturbances, 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 which may lead to fainting;
• shortness of breath during physical activity;
• cough;
• hiccups;
• ringing in the ears, ear discomfort;
• intestinal or stomach bleeding;
• heartburn;
• stomach pain, bloating;
• difficulty swallowing;
• infection or inflammation of the stomach and intestine;
• stomach pain;
• irritation of the mouth or lips, sore throat;
• altered liver function;
• skin itching;
• 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;
• general feeling of discomfort;
• loss of body weight;
• increase in body weight.

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/fainting, 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;
• lung disorders that prevent your body from receiving enough oxygen. These may 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);
• cysts in the eyes (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);
• severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at
www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bortezomib Aurobindo

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 carton after Exp.
Store the vial in the outer carton to protect the medicine from light.

Intravenous administration:
Reconstituted solution 1 mg/ml.
Do not refrigerate.
Chemical and physical in-use stability has been demonstrated for 7 days at 25°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.

Subcutaneous administration:
Reconstituted solution 2.5 mg/ml.
Do not refrigerate.
Chemical and physical in-use stability has been demonstrated for 7 days at 25°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately.
If not used immediately, the conditions and duration of in-use storage are the responsibility of the user.

Bortezomib Aurobindo is for single use only. Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What Bortezomib Aurobindo contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol boronic ester).
• The other component is mannitol.

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

Description of the appearance of Bortezomib Aurobindo and contents of the pack
White to almost white lyophilised powder or cake.
Each pack of Bortezomib Aurobindo 3.5 mg powder for injectable solution contains 1 type I glass vial of 10 ml, with a grey bromobutyl stopper, aluminium seal and polypropylene disc.
Pack sizes: 1, 3, 5, 10 vials with or without plastic protective overwrap.

Marketing Authorisation Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront, Floriana FRN 1914, Malta

Manufacturer
APL Swift Services (Malta) Ltd
HF26, Hal Far Industrial Estate, Hal Far,
Birzebbugia, Malta
Generis Farmacêutica S.A.
Rua Joao De Deus, n. 19
Venda Nova, Amadora, Portugal
Arrow Generiques
26 avenue Tony Garnier
Lyon, France

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium: Bortezomib Eugia 3.5 mg poeder voor oplossing voor injectie /poudre pour solution injectable/ Pulver zur Herstellung einer Injektionslösung
France: Bortezomib Arrow 3.5 mg poudre pour solution injectable
Germany: Bortezomib Puren 3.5 mg Pulver zur Herstellung einer Injektionslösung
Italy: Bortezomib Aurobindo
Netherlands: Bortezomib Eugia 3.5 mg, poeder voor oplossing voor injectie
Poland: Bortezomib Eugia
Portugal: Bortezomib Generis
Spain: Bortezomib Aurovitas 3.5 mg polvo para solución inyectable EFG

The following information is intended exclusively for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Aurobindo 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 PRESERVATIVES, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING HANDLING OF BORTEZOMIB AUROBINDO.
1.1 Reconstitution of the 3.5 mg vial: carefully add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride injectable solution to the vial containing Bortezomib Aurobindo lyophilized powder, using a syringe of appropriate size, without removing the vial stopper. The lyophilized powder dissolves completely in 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 prior to administration to check for the presence of particulate matter or discoloration. If discoloration or particulate matter is observed, the solution must not be used and should 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. However, the in-use chemical and physical stability of the reconstituted solution has been demonstrated for 7 days at 25°C in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 7 days before administration. If the reconstituted solution is not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.
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 to 5 seconds through a peripheral or central intravenous catheter.
• Flush the intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution for injection.

Bortezomib Aurobindo 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. 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
applicable local regulations.

The following information is intended exclusively for healthcare professionals:

Only the 3.5 mg vial can be administered by subcutaneous route, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Aurobindo 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 PRESERVATIVES, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING HANDLING OF BORTEZOMIB AUROBINDO.
1.1 Reconstitution of the 3.5 mg vial: carefully add 1.4 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib Aurobindo lyophilized powder, using a syringe of appropriate size, 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 prior to administration for presence of particulate matter or discoloration. If discoloration or particulate matter is observed, the solution must not be used and should be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).
1.3 The reconstituted solution contains no preservatives and should be used immediately after preparation. However, chemical and physical in-use stability of the reconstituted solution has been demonstrated for 7 days at 25°C in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 7 days before administration. If the reconstituted solution is not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.
There is no need to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

• After dissolution, 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).
• 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, the injection site must be rotated.
• If local reactions occur at the injection site after subcutaneous administration of Bortezomib Aurobindo, a lower concentration of Bortezomib Aurobindo solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

Bortezomib Aurobindo 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. 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.