Bortezomib Sun

Package leaflet: Information for the user

Bortezomib SUN 3.5 mg powder for solution for injection

bortezomib

Read 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, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Bortezomib SUN contains the active substance bortezomib, a so-called "proteasome inhibitor".
Proteasomes play an important role in regulating cell functions and cell growth.
By interfering with their function, bortezomib can kill tumour cells.
Bortezomib SUN is used to treat:

• multiple myeloma (a type of malignant neoplasm of the bone marrow) in patients over 18 years of age:
• alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients with progressive disease after having received at least one prior therapy or in whom blood stem cell transplantation has failed or is not feasible
• in combination with melphalan and prednisone, for previously untreated patients who are not eligible for high-dose chemotherapy with blood stem cell transplantation
• in combination with dexamethasone or dexamethasone plus thalidomide, for previously untreated patients prior to receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment)
• mantle cell lymphoma (a type of malignant neoplasm affecting the lymph nodes) in patients 18 years of age or older. In this case, Bortezomib SUN is used in combination with rituximab, cyclophosphamide, doxorubicin and prednisone, for previously untreated patients who are not eligible for blood stem cell transplantation.

2. What you need to know before taking Bortezomib SUN

Do not take Bortezomib SUN

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

Warnings and precautions
Tell your doctor if you have:

• low red blood cell or white blood cell count
• 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 nerve problems such as numbness, tingling, or pain in the hands or feet (neuropathy)
• heart disorder or blood pressure problems
• shortness of breath or cough
• seizures
• herpes zoster (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 to have regular blood tests before and during treatment with Bortezomib SUN to monitor your blood cell counts.
If you have mantle cell lymphoma and are being treated with rituximab together with Bortezomib SUN, 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 experience a reactivation of the disease, which can be fatal. If you have previously had hepatitis B infection, your doctor will need to monitor you closely for signs and symptoms of active hepatitis B.

Read the package leaflets of all the medicines you are taking in combination with Bortezomib SUN for information about these medicines before starting treatment with Bortezomib SUN.
When Bortezomib SUN is administered together with the medicine thalidomide, 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 SUN must not be used in children and adolescents because it is not known how the medicine works in these patients.
Other medicines and Bortezomib SUN
Tell 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 medicines.

Pregnancy and breastfeeding
You must not use Bortezomib SUN during pregnancy unless strictly necessary.
You must not breastfeed during treatment with Bortezomib SUN. 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 SUN is administered together with thalidomide, you must follow the thalidomide pregnancy prevention programme (see the thalidomide package leaflet).
Contraception
Men and women receiving treatment with Bortezomib SUN must use effective contraceptive methods during treatment and for up to 3 months after treatment ends. If pregnancy occurs despite these precautions, inform your doctor immediately.
Driving and using machines
Bortezomib SUN may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate machinery if you experience any of these symptoms. Exercise particular caution even if these effects do not occur.

3. How to use Bortezomib SUN

Your doctor will calculate the dose of Bortezomib SUN based on your height and weight. The standard starting dose of Bortezomib SUN is 1.3 mg/m^2 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 SUN is given alone, you will receive 4 doses of Bortezomib SUN 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) constitutes one treatment cycle. You may receive up to 8 cycles (24 weeks of treatment).

You may also receive Bortezomib SUN in combination with pegylated liposomal doxorubicin or dexamethasone:

• When Bortezomib SUN is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib SUN given intravenously or subcutaneously. Pegylated liposomal doxorubicin is administered at a dose of 30 mg/m^2 on day 4 of the 21-day Bortezomib SUN treatment cycle, via intravenous infusion after the Bortezomib SUN injection. You may receive up to 8 cycles (24 weeks of treatment).
• When Bortezomib SUN is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib SUN given intravenously or subcutaneously. Dexamethasone is administered orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib SUN 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 you are not eligible for blood stem cell transplantation, you will receive Bortezomib SUN 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 SUN is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5–9, Bortezomib SUN is administered once weekly on days 1, 8, 22, and 29. Melphalan (9 mg/m^2) and prednisone (60 mg/m^2) 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 blood stem cell transplantation, you will receive Bortezomib SUN intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

• When Bortezomib SUN is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib SUN given intravenously or subcutaneously. Dexamethasone is administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib SUN treatment cycle. You will receive 4 cycles (12 weeks).
• When Bortezomib SUN is administered together with thalidomide and dexamethasone, the treatment cycle duration is 28 days (4 weeks). Dexamethasone is administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib SUN treatment cycle. 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 previously received specific treatment for mantle cell lymphoma, you will receive Bortezomib SUN intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib SUN 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 SUN treatment cycle as intravenous infusions:
rituximab at a dose of 375 mg/m^2, cyclophosphamide at a dose of 750 mg/m^2, and doxorubicin at a dose of 50 mg/m^2.
Prednisone is administered orally at a dose of 100 mg/m^2 on days 1, 2, 3, 4, and 5 of the Bortezomib SUN treatment cycle.

How Bortezomib SUN is administered
This medicine is for intravenous or subcutaneous use. Bortezomib SUN will be administered by a healthcare professional experienced in the use of cytotoxic medicines.
The Bortezomib SUN powder 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, administered over 3 to 5 seconds. The subcutaneous injection can be given either in the thigh or the abdomen.

If you receive more Bortezomib SUN 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 for any side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these effects can be serious.
Contact 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 chest tightness.

Treatment with Bortezomib SUN 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 regular blood tests before and during treatment with Bortezomib SUN to monitor your blood cell counts continuously. 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 can cause anaemia, with symptoms such as fatigue and paleness
• white blood cells, which may increase your susceptibility to infections or flu-like symptoms.

Multiple myeloma
If you are being treated with Bortezomib SUN for multiple myeloma, the possible side effects are listed below.
Very common side effects (may affect more than 1 in 10 people)

• skin sensitivity, numbness, tingling or burning sensation, 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 to drink much more water than usual. Your doctor may prescribe medication 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
• increased blood pressure
• reduced kidney function
• headache
• general feeling of malaise, pain, dizziness, feeling of emptiness in the head, 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 over the body)
• chest pain or difficulty breathing during physical activity
• various types of skin rash
• skin itching, skin nodules or dry skin
• facial redness or small capillary ruptures
• skin redness
• dehydration
• heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding
• altered liver function
• irritation of the mouth or lips, dry mouth, oral 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)
• epistaxis (nosebleed)
• sleep disturbances or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, mental state changes, 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
• vein inflammation, 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 mucosal bleeding, for example from mouth or vagina
• cerebrovascular disorders
• paralysis, seizures, falls, movement disorders, abnormal, altered or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, spasms
• arthritis, including inflammation of the joints of the fingers, toes and jaw
• lung disorders, preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow, difficult or interrupted breathing, wheezing
• Hiccups, speech disorders
• increased or decreased urine production (kidney damage), pain during urination or presence of blood/protein in urine, fluid retention
• altered levels of consciousness, confusion, memory failure or loss
• hypersensitivity
• hearing loss, deafness or ringing in the ears (tinnitus), ear discomfort
• hormonal changes that may affect 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
• swollen lymph nodes
• joint or muscle stiffness, heaviness sensation, 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 obstruction), abdominal or oesophageal discomfort, difficulty swallowing, vomiting with blood
• skin infections
• bacterial and viral infections
• dental infections
• pancreatitis, bile duct obstruction
• genital pain, erectile problems
• weight gain
• feeling thirsty
• hepatitis
• injection site or catheter site reactions
• skin reactions or disorders (which may be severe and life-threatening), skin ulceration
• 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 under 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, ear bleeding
• reduced activity of the thyroid gland
• Budd-Chiari syndrome (clinical signs caused by blockage of the liver veins)
• altered or abnormal intestinal function
• cerebral haemorrhage (bleeding in the brain)
• 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/weakness, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat that 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 similar to psoriasis
• skin tumour
• skin pallor
• increased platelets or plasma cells (a type of white blood cell) in the blood
• blood clotting in small blood vessels (thrombotic microangiopathy)
• abnormal reaction to blood transfusion
• partial or complete loss of vision
• decreased libido
• loss of saliva
• eye protrusion
• photophobia (excessive sensitivity of the eye to light)
• rapid breathing
• rectal pain
• gallstones
• hernia
• injuries
• brittle or weak nails
• abnormal protein deposition in vital organs
• coma
• intestinal ulcers
• multi-organ damage
• death.

Mantle cell lymphoma
If you are being treated with Bortezomib SUN 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
• skin sensitivity, numbness, tingling or burning sensation, 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 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 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, which may lead to fainting
• shortness of breath during physical activity
• cough
• hiccups
• ringing in the ears (tinnitus), 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 malaise
• loss of body weight
• gain 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/weakness, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat that may cause difficulty swallowing, collapse
• movement disorders, paralysis, contractions
• vertigo
• hearing loss, deafness
• lung disorders, preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow, difficult or interrupted breathing, 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 clotting 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 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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bortezomib SUN

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 the outer carton after EXP.
Store below 25°C. Keep the vial in the outer packaging to protect the medicine from light.
From a microbiological standpoint, the reconstituted solution should be used immediately after preparation.
If the reconstituted solution is not used immediately after preparation, it is the responsibility of the user to ensure appropriate storage conditions and duration prior to use. However, the reconstituted solution is stable for 8 hours at 25°C prior to administration when stored in the original vial and/or in a syringe, with a maximum storage time for the reconstituted medicine not exceeding 8 hours.
Bortezomib SUN 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 SUN contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol boronic ester).
• The excipient is mannitol (E421).

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 SUN and contents of the pack
Bortezomib SUN 3.5 mg powder for injectable solution is a white to off-white powder or solid.
Each pack of Bortezomib SUN contains one 10 ml clear glass vial with a light green aluminium cap, packed in a transparent blister.

Marketing Authorisation Holder and Manufacturer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien/България/Česká republika/
Danmark/Eesti/Ελλάδα/Hrvatska/Ireland/Ísland/Κύπρος/
Latvija/Lietuva/Luxembourg/Luxemburg/Magyarország/
Malta/Nederland/Norge/Österreich/Portugal/
Slovenija/Slovenská republika/Suomi/Finland/Sverige
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Nederland/Pays-Bas/Niederlande/Нидерландия/Nizozemsko/
Nederlandene/Holland/Ολλανδία/Nizozemska/The Netherlands/Holland/Ολλανδία/
Nīderlande/Nyderlandai/Pays-Bas/Niederlande/Hollandia/
L-Olanda/Nederland/Nederland/Niederlande/Países Baixos/
Nizozemska/Holandsko/Alankomaat/Nederländerna/Nederländerna
Tel./тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./
+31 (0)23 568 5501

Deutschland
Sun Pharmaceuticals Germany GmbH
Hemmelrather Weg 201
51377 Leverkusen
Germany
tel. +49 (0) 214 403 99 192

España
Sun Pharma Laboratorios, S.L.
Rambla de Catalunya 53-55
08007 Barcelona
Spain
tel. +34 93 342 78 90

France
Sun Pharma France
11-15, Quai de Dion Bouton
92800 Puteaux
France
tel. +33 1 41 44 44 50

Italia
Sun Pharma Italia Srl
Viale Giulio Richard, 1
20143 Milano
Italy
tel. +39 02 33 49 07 93

Polska
Ranbaxy (Poland) Sp. Z o. o.
ul. Kubickiego 11
02-954 Warszawa
Poland
Tel. +48 22 642 07 75

România
Terapia S.A.
Str. Fabricii nr 124
Cluj-Napoca, Judeţul Cluj
Romania
Tel. +40 (264) 501 500

United Kingdom (Northern Ireland)
Ranbaxy UK Ltd
a Sun Pharma Company
Millington Road 11
Hyde Park, Hayes 3
5th Floor
Hayes
UB3 4AZ HAYES
United Kingdom
tel. +44 (0) 208 848 8688

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib SUN 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 SUN.

1.1 Reconstitution of the 3.5 mg vial: carefully add 3.5 ml of sterile injectable sodium chloride solution 9 mg/ml (0.9%) to the vial containing Bortezomib SUN lyophilized powder, using an appropriate syringe and 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. It is not necessary 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.
Confirm the concentration on the vial label to ensure that the correct dose is administered by intravenous route (1 mg/ml).

1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution has been demonstrated for 8 hours at 25 °C when stored in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 8 hours prior to administration. If the reconstituted solution is not used immediately after preparation, it is the responsibility of the user to ensure appropriate storage conditions and storage times before use.
It is not necessary 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 as an intravenous bolus over 3–5 seconds using a peripheral or central intravenous catheter.
• Flush the intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution for injection.

Bortezomib SUN 3.5 mg powder for solution for injection is for SUBCUTANEOUS or
INTRAVENOUS use only. Do not administer by other routes. Intrathecal administration has
resulted in death.

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 regulations.
The following information is intended for healthcare professionals only:
Only the 3.5 mg vial can be administered subcutaneously as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib SUN 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 SUN.
1.1 Preparation of the 3.5 mg vial: carefully add 1.4 ml of sterile injectable sodium chloride solution 9 mg/ml (0.9%) to the vial containing Bortezomib SUN powder, using an appropriate syringe and 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 must 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.
Confirm the concentration on the vial label to ensure that the correct dose is administered by subcutaneous route (2.5 mg/ml).
1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution has been demonstrated for 8 hours at 25 °C when stored in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 8 hours prior to administration. If the reconstituted solution is not used immediately after preparation, it is the responsibility of the user to ensure that the storage conditions and duration are respected before use.
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).
• Inject the solution by subcutaneous route 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 SUN, administration of a lower concentration of Bortezomib SUN solution (1 mg/ml instead of 2.5 mg/ml) may be considered, or switching to intravenous injection is recommended.

Bortezomib SUN 3.5 mg powder for solution for injection 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.