VELCADE 3.5 MG Инъекционный раствор

Содержание инструкции

1. VELCADE 1 mg powder for injectable solution
   1. What is VELCADE and what is it used for
   2. What you need to know before you use VELCADE
   3. How to use VELCADE
   4. Possible side effects
   5. How to store VELCADE
   6. Package contents and other information
   7. RECONSTITUTION FOR INTRAVENOUS INJECTION
   8. ADMINISTRATION
   9. DISPOSAL
2. VELCADE 3,5 mg powder for injectable solution
   1. What is VELCADE and what is it used for
   2. What you need to know before using VELCADE
   3. How to use VELCADE
   4. Possible side effects
   5. How to store VELCADE
   6. Package Contents and Other Information
   7. RECONSTITUTION FOR INTRAVENOUS INJECTION
   8. ADMINISTRATION
   9. DISPOSAL
   10. RECONSTITUTION FOR SUBCUTANEOUS INJECTION
   11. ADMINISTRATION
   12. DISPOSAL

VELCADE 1 mg powder for injectable solution

bortezomib

Read this leaflet carefully before you start to use this medicine as it contains important
information for you.

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

Contents of this leaflet:

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

1. What is VELCADE and what is it used for

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

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

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

2. What you need to know before you use VELCADE

Do not use VELCADE

• 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
Tell your doctor if you have:

• a low number of red blood cells or white blood cells
• bleeding problems and/or a low number of platelets in your blood
• diarrhoea, constipation, nausea or vomiting
• previously experienced fainting, dizziness or a feeling of lightheadedness
• kidney problems
• moderate to severe liver problems
• previously experienced disorders such as numbness, tingling or pain in your hands or feet (neuropathy)
• heart or blood pressure problems
• shortness of breath or cough
• convulsions
• herpes zoster(even if localised around the eyes or spreading to the rest of the body)
• symptoms of tumour lysis syndrome such as, for example, 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 checks.

You will need to have regular blood tests before and during treatment with VELCADE, to
constantly monitor your blood cell counts.
If you have mantle cell lymphoma and are given rituximab together with VELCADE, you must tell your
doctor:

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

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

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

Other medicines and VELCADE
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
In particular, tell your doctor if you are using medicines containing any of the following active substances:

• ketoconazole, used to treat fungal infections
• ritonavir, used to treat HIV infection
• rifampicin, an antibiotic used to treat bacterial infections
• carbamazepine, phenytoin or phenobarbital, used to treat epilepsy
• St John's Wort ( Hypericum perforatum), used to treat depression or other conditions
• oral antidiabetics

Pregnancy and breastfeeding
You must not use VELCADE if you are pregnant, unless strictly necessary.
Women of childbearing potential must use effective contraceptive measures during treatment and for
8 months after the end of treatment. Talk to your doctor if you wish to freeze your eggs before
starting treatment.
Men must not father a child during treatment with VELCADE and must use
an effective contraceptive method during treatment and for 5 months after the end of
treatment. Talk to your doctor if you wish to store sperm before starting treatment.
You must not breastfeed during treatment with VELCADE. Discuss with your doctor the most
appropriate time to restart breastfeeding after stopping therapy.
The medicine thalidomide causes birth defects and fetal death. When VELCADE is given
together with thalidomide, you must follow the thalidomide pregnancy prevention programme

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

3. How to use VELCADE

The doctor will calculate the dose of VELCADE in proportion to your height and weight. The standard initial dose of VELCADE is 1.3 mg/m of body surface area twice a week. The doctor may change the dose and the total number of treatment cycles based on your response to treatment, the occurrence of certain side effects, and your overall health conditions (e.g., liver problems).

Multiple myeloma in progression
When VELCADE is administered alone, you will receive 4 doses of VELCADE intravenously on days 1, 4, 8 and 11. This is followed by a “pause” period of 10 days without treatment. This period of 21 days (3 weeks) corresponds to a treatment cycle. You may receive up to 8 cycles (24 weeks).
You may also receive VELCADE together with the medications pegylated liposomal doxorubicin or dexamethasone.
When VELCADE is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with VELCADE intravenously and 30 mg/m of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day VELCADE treatment cycle as an intravenous infusion after the VELCADE injection.
You may receive up to 8 cycles (24 weeks of treatment).
When VELCADE is administered together with dexamethasone you will receive a 21-day treatment cycle with VELCADE intravenously and dexamethasone orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of the 21-day VELCADE treatment cycle.
You may receive up to 8 cycles (24 weeks of treatment).

Multiple myeloma previously untreated
If you have never been treated before for multiple myeloma and you are noteligible for blood stem cell transplantation, you will receive VELCADE intravenously together with two other medications: melphalan and prednisone.
In this case, the duration of a treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1-4, VELCADE is administered twice a week on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5-9, VELCADE is administered once a week 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 areeligible for blood stem cell transplantation, you will receive VELCADE intravenously together with the medications: dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When VELCADE is administered together with dexamethasone, you will receive a 21-day treatment cycle with VELCADE intravenously and dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day VELCADE treatment cycle.
You will receive 4 cycles (12 weeks of treatment).
When VELCADE is administered together with thalidomide and dexamethasone, the duration of the treatment cycle is 28 days (4 weeks).
Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 28-day VELCADE treatment cycle and thalidomide is administered daily orally at a dose of 50 mg up to day 14 of the first cycle and, if tolerated, the dose of thalidomide is increased to 100 mg on days 15-28 and may be subsequently increased to 200 mg per day from the second cycle onwards. You may receive up to 6 cycles (24 weeks of treatment).

Mantle cell lymphoma previously untreated
If you have never received specific treatment for mantle cell lymphoma in the past, you will receive VELCADE intravenously together with the medications rituximab, cyclophosphamide, doxorubicin and prednisone.
VELCADE is administered intravenously on days 1, 4, 8 and 11, followed by a period of “rest” without treatment. The duration of the treatment cycle is 21 days (3 weeks). You may receive up to 8 treatment cycles (24 weeks).
The following medications are administered on day 1 of each 21-day VELCADE treatment cycle as an intravenous infusion:
Rituximab at 375 mg/m, cyclophosphamide at 750 mg/m and doxorubicin at 50 mg/m.
Prednisone is administered orally at a dose of 100 mg/m on days 1, 2, 3, 4 and 5 of the VELCADE treatment cycle.

How VELCADE is administered
This medication is for intravenous use only. VELCADE will be administered by a healthcare professional experienced in the use of cytotoxic medications.
VELCADE powder must be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then injected rapidly into a vein, over a period of 3 to 5 seconds.

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

4. Possible side effects

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

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

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

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

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

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

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

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

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

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate, high blood pressure
• Kidney failure
• Inflammation of a vein, blood clots in the veins and lungs
• Blood clotting problems
• Impaired circulation
• Inflammation of the membrane surrounding the heart or presence of fluid around the heart
• Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis
• Blood in the stool, or bleeding from the mucous membranes for example mouth, vagina
• Cerebrovascular disorders
• Paralysis, seizures, falls, movement disorders, abnormal sensitivity, altered or reduced (feeling, hearing, tasting, smelling), attention disorder, tremor, spasms
• Arthritis, including inflammation of the joints of the fingers, toes and jaw
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, wheezing even without physical activity, shallow or labored breathing, or needing to stop
• Hiccups, speech disorders
• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in the urine, fluid retention
• Altered levels of consciousness, confusion, memory impairment or loss
• Hypersensitivity
• Hearing loss, deafness or ringing in the ears, ear discomfort
• Hormonal changes that can affect the reabsorption of salts and water
• Hyperactivity of the thyroid gland
• Inability to produce enough insulin or resistance to normal levels of insulin
• Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, swelling of the eyelid (chalazion), red and swollen eyelids, eye discharge, vision disorders, 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, ulcers of the mouth, esophagus, stomach and intestines sometimes associated with pain or bleeding, reduced intestinal motility (including bowel obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood
• Skin infections
• Bacterial and viral infections
• Dental infection
• Inflammation of the pancreas, obstruction of the bile ducts
• Genital pain, erectile dysfunction
• Weight gain
• Feeling of thirst
• Hepatitis
• Disorders at the injection site or catheter site
• Skin reactions or disorders (which can be severe and life-threatening), skin ulcerations
• Bruises, falls and injuries
• Inflammation or bleeding of blood vessels that can manifest with small red or purple spots (usually on the legs) that can become like large bruises on the skin or tissues
• Benign cysts
• A serious and reversible condition of the brain that includes 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 can cause paralysis and difficulty breathing (Guillain-Barré syndrome)
• Hot flashes
• Alteration of the color of the veins
• Inflammation of the spinal nerve
• Ear problems, bleeding from the ear
• Reduced activity of the thyroid gland
• Budd-Chiari syndrome (clinical signs are caused by blockage of the liver veins)
• Change or abnormal bowel function
• Cerebral hemorrhage
• Yellowing of the eyes and skin (jaundice)
• Swelling of the eyelid (chalazion), red and swollen eyelids

If you are given VELCADE together with other medicines for the treatment of mantle
cell lymphoma, the side effects that may occur are listed below:

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

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

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

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

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

• Hepatitis
• Severe allergic reaction (anaphylactic reaction) whose signs may include difficulty breathing, chest pain or tightness, and/or feeling dizzy/weak, severe itching of the skin or appearance of swelling on the skin, swelling of the face, lips, tongue and/or throat that can cause difficulty swallowing, collapse
• Movement disorders, paralysis, contractions
• Dizziness
• Hearing loss, deafness
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, wheezing even without physical activity, breathing that becomes shallow, labored or stops, wheezing
• Blood clots in the lungs
• Yellowing of the eyes and skin (jaundice)
• Swelling of the eyelid (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 can cause paralysis and difficulty breathing (Guillain-Barré syndrome)

Reporting of undesirable effects
If you experience any undesirable effect, including those not listed in this leaflet, please contact
your doctor or pharmacist. You can also report undesirable effects directly through the
national reporting system described in Annex V. By reporting undesirable effects, you can
contribute to providing more information on the safety of this medicine.

5. How to store VELCADE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and the package after
EXP.
Store at a temperature not exceeding 30°C. Keep the vial in the outer packaging to
protect the medicine from light.
The reconstituted solution must be used immediately after preparation. If the reconstituted solution
is not used immediately, conditions and times of use are the responsibility of the
preparer. However, the reconstituted solution is stable for 8 hours at 25°C before
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.
VELCADE is for single use. Unused product and waste must be disposed of in accordance with
current local regulations.

6. Package contents and other information

What VELCADE contains

• The active ingredient is bortezomib .Each vial contains 1 mg of bortezomib (as the boron mannitol ester). After reconstitution, 1 ml of injectable solution contains 1 mg of bortezomib.
• The excipients are mannitol (E421) and nitrogen.

Description of the appearance of VELCADE and package contents
VELCADE 1 mg or 3.5 mg powder for injectable solution is a powder ranging in color from white to
white-cream.
Each pack of VELCADE 1 mg contains 1 glass vial with a green-colored closing cap,
contained in a transparent blister.

Marketing authorization holder:
JANSSEN-CILAG INTERNATIONAL NV
Turnhoutseweg, 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg, 30
B-2340 Beerse
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorization holder.

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
[email protected]

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: 0800 086 9247 /+49 2137 955 6955
[email protected]

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
[email protected]

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
[email protected]

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη
Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
[email protected]

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tél: 0 800 25 50 75 / + 33 1 55 00 40 03
[email protected]

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122
[email protected]

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
[email protected]

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
[email protected]

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

United Kingdom
(Northern Ireland)
Janssen Sciences Ireland UC
Tel: +44 1 494 567 444
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines
Agency https://www.ema.europa.eu.
The following information is intended exclusively for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: VELCADE is a cytotoxic agent. Consequently, particular attention must be paid during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE RULES MUST BE FOLLOWED DURING THE HANDLING OF VELCADE.

• 1.1 Preparation of the 1 mg vial: carefully add 1 mlof sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing VELCADE powder using a 1 ml syringe and 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
colorless with a final pH between 4 and 7. It is not necessary to check the pH of the solution.

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or color change. If particulate matter or color change is present, the solution must not be used and must be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered intravenously (1 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 for a maximum of 8 hours in the syringe. The total storage time of the reconstituted medicine must not exceed 8 hours before administration. If the reconstituted solution is not used immediately after preparation, it is the user's responsibility to comply with the storage conditions and times of the product before use.

The reconstituted medicine does not need to be protected from light.

2. ADMINISTRATION

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

VELCADE 1 mg powder for injectable solution IS FOR INTRAVENOUS USE ONLY. Do not
administer via other routes. Intrathecal administration has resulted in death.

3. DISPOSAL

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

VELCADE 3,5 mg powder for injectable solution

bortezomib

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

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

Contents of this leaflet:

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

1. What is VELCADE and what is it used for

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

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

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

2. What you need to know before using VELCADE

Do not use VELCADE

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

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

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

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

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

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

Other medicines and VELCADE
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
In particular, tell your doctor if you are using medicines containing any of the following active substances:

• ketoconazole, used to treat fungal infections
• ritonavir, used to treat HIV infection
• rifampicin, an antibiotic used to treat bacterial infections
• carbamazepine, phenytoin or phenobarbital, used to treat epilepsy
• St John's wort ( Hypericum perforatum), used to treat depression or other conditions
• oral antidiabetics.

Pregnancy and breastfeeding
You must not use VELCADE if you are pregnant, unless strictly necessary.
Women of childbearing potential must use effective contraceptive measures during treatment and for
8 months after the end of treatment. Talk to your doctor if you want to freeze your eggs before
starting treatment.
Men must not father a child during treatment with VELCADE and must use
an effective contraceptive method during treatment and for 5 months after the end of
treatment. Talk to your doctor if you want to store sperm before starting treatment.
You must not breastfeed while taking VELCADE. Discuss with your doctor the most
appropriate time to start breastfeeding again after the end of therapy.
The medicine thalidomide causes birth defects and fetal death. When VELCADE is given
together with thalidomide, you must follow the thalidomide pregnancy prevention program

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

3. How to use VELCADE

The doctor will calculate the dose of VELCADE in proportion to your height and weight. The standard initial dose of VELCADE is 1.3 mg/m of body surface area twice a week. The doctor may change the dose and the total number of treatment cycles based on your response to treatment, the occurrence of certain side effects, and your overall health conditions (e.g., liver problems).

Multiple myeloma in progression
When VELCADE is administered alone, you will receive 4 doses of VELCADE intravenously or subcutaneously on days 1, 4, 8 and 11. This is followed by a “pause” period of 10 days without treatment. This period of 21 days (3 weeks) corresponds to a treatment cycle. You may receive up to 8 cycles (24 weeks).
You may also receive VELCADE together with the medications pegylated liposomal doxorubicin or dexamethasone.
When VELCADE is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with VELCADE intravenously or subcutaneously and 30 mg/m of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day treatment cycle of VELCADE as an intravenous infusion after the injection of VELCADE.
You may receive up to 8 cycles (24 weeks of treatment).
When VELCADE is administered together with dexamethasone you will receive a 21-day treatment cycle with VELCADE intravenously or subcutaneously and dexamethasone orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of the 21-day treatment cycle with VELCADE.
You may receive up to 8 cycles (24 weeks of treatment).

Multiple myeloma previously untreated
If you have never been treated before for multiple myeloma and you are noteligible for blood stem cell transplantation, you will receive VELCADE together with two other medications: melphalan and prednisone.
In this case, the duration of a treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1-4, VELCADE is administered twice a week on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5-9, VELCADE is administered once a week on days 1, 8, 22 and 29. Melphalan (9 mg/m ) and prednisone (60 mg/m ) are administered orally on days 1, 2, 3 and 4 of the first week of each cycle.

If you have never been treated before for multiple myeloma and you areeligible for blood stem cell transplantation, you will receive VELCADE intravenously or subcutaneously together with the medications: dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When VELCADE is administered together with dexamethasone, you will receive a 21-day treatment cycle with VELCADE intravenously or subcutaneously and dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day treatment cycle of VELCADE.
You will receive 4 cycles (12 weeks of treatment).
When VELCADE is administered together with thalidomide and dexamethasone, the duration of the treatment cycle is 28 days (4 weeks).
Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 28-day treatment cycle with VELCADE and thalidomide is administered daily orally at a dose of 50 mg up to day 14 of the first cycle and, if tolerated, the dose of thalidomide is increased to 100 mg on days 15-28 and may be subsequently increased to 200 mg per day from the second cycle onwards. You may receive up to 6 cycles (24 weeks of treatment).

Mantle cell lymphoma previously untreated
If you have never received specific treatment for mantle cell lymphoma in the past, you will receive VELCADE intravenously or subcutaneously together with the medications rituximab, cyclophosphamide, doxorubicin and prednisone.
VELCADE is administered intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a “rest” period without treatment. The duration of the treatment cycle is 21 days (3 weeks).
You may receive up to 8 treatment cycles (24 weeks).
The following medications are administered on day 1 of each 21-day treatment cycle of VELCADE as an intravenous infusion: rituximab at 375 mg/m , cyclophosphamide at 750 mg/m and doxorubicin at 50 mg/m .
Prednisone is administered orally at a dose of 100 mg/m on days 1, 2, 3, 4 and 5 of the treatment cycle with VELCADE.

How VELCADE is administered
This medication is for intravenous or subcutaneous use. VELCADE will be administered by a healthcare professional experienced in the use of cytotoxic medications.
VELCADE powder must be dissolved 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, over a period of time from 3 to 5 seconds. The subcutaneous injection can be performed either in the thigh or in the abdomen.

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

4. Possible side effects

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

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

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

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

If you are given VELCADE 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)

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

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

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

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

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• Kidney failure.
• Inflammation of a vein, blood clots in the veins and lungs.
• Blood clotting problems.
• Circulatory failure.
• Inflammation of the membrane surrounding the heart or presence of fluid around the heart.
• Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis.
• Blood in the stool, or bleeding of the mucous membranes for example mouth, vagina.
• Cerebrovascular disorders.
• Paralysis, convulsions, falls, movement disorders, abnormal sensitivity, altered or reduced (feeling, hearing, tasting, smelling), attention disorder, tremor, spasms.
• Arthritis, including inflammation of the joints of the fingers and toes and jaw.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, rapid breathing even without physical activity, shallow, difficult breathing or the need to stop, wheezing.
• Hiccups, speech disorders.
• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in the urine, fluid retention.
• Altered levels of consciousness, confusion, memory impairment or loss.
• Hypersensitivity.
• Hearing loss, deafness or ringing in the ears, ear discomfort.
• Hormonal changes that may affect the reabsorption of salts and water.
• Hyperactivity of the thyroid gland.
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, swelling of the eyelid (chalazion), red and swollen eyelids, eye discharge, vision disorders, bleeding of the eyes.
• Swollen lymph nodes.
• Joint or muscle stiffness, feeling of heaviness, groin pain.
• Hair loss or abnormal hair texture.
• Allergic reactions.
• Redness or pain at the injection site.
• Mouth pain.
• Infection or inflammation of the mouth, ulcers of the mouth, esophagus, stomach and intestines sometimes associated with pain or bleeding, reduced intestinal motility (including bowel obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood.
• Skin infections.
• Bacterial and viral infections.
• Dental infection.
• Inflammation of the pancreas, blockage of the bile ducts.
• Genital pain, problems with erection.
• Weight gain.
• Feeling thirsty.
• Hepatitis.
• Disorders at the injection site or catheter site.
• Skin reactions or disorders (which can be severe and life-threatening), skin ulcerations.
• Bruises, falls and injuries.
• Inflammation or bleeding of blood vessels that can manifest with small red or purple spots (usually on the legs) that can become like large bruises on the skin or tissues.
• Benign cysts.
• A serious and reversible condition of the brain that includes convulsions, high blood pressure, headache, fatigue, confusion, blindness or other vision problems.

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

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

If you are given VELCADE together with other medicines for the treatment of mantle cell
lymphoma, the side effects that may occur are listed below:

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

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

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

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

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

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction) whose signs may include difficulty breathing, chest pain or tightness, and/or feeling dizzy/weak, severe itching of the skin or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat that can cause difficulty in swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Dizziness.
• Hearing loss, deafness.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, rapid breathing even without physical activity, breathing that becomes shallow, difficult or stops, wheezing.
• Blood clots in the lungs.
• Yellowing of the eyes and skin (jaundice).
• Swelling of the eyelid (chalazion), red and swollen eyelids.

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

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

Reporting of undesirable effects
If you experience any undesirable effects, including those not listed in this leaflet, please contact
your doctor or pharmacist. You can also report undesirable effects directly through the
national reporting system detailed in Annex V. By reporting undesirable effects you can
contribute to providing more information on the safety of this medicine.

5. How to store VELCADE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is reported on the vial and on the package after
EXP.
Store at a temperature not exceeding 30°C. Keep the vial in the outer packaging to
protect the medicine from light.
The reconstituted solution must be used immediately after preparation. If the reconstituted solution
is not used immediately, conditions and times of use are the responsibility of the
preparer. However, the reconstituted solution is stable for 8 hours at 25°C before
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.
VELCADE is for single use. Unused product and waste must be disposed of in accordance with
current local regulations.

6. Package Contents and Other Information

What VELCADE contains

• The active ingredient is bortezomib .Each vial contains 3.5 mg of bortezomib (as a mannitol boronic ester). After reconstitution, 1 ml of injectable solution contains 1 mg of bortezomib.
• The excipients are mannitol (E421) and nitrogen.

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

Description of the appearance of VELCADE and contents of the pack
VELCADE powder for solution for injection is from white to off-white in color.
Each pack of VELCADE 3.5 mg contains 1 glass vial of 10 ml with a blue-colored closing cap
contained in a transparent blister.

Marketing Authorization Holder:
JANSSEN-CILAG INTERNATIONAL NV
Turnhoutseweg, 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg, 30
B-2340 Beerse
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorization holder.

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
[email protected]

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: 0800 086 9247 / +49 2137 955 6955
[email protected]

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
[email protected]

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
[email protected]

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη
Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
[email protected]

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
[email protected]

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122
[email protected]

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
Tel:800.688.777 / +39 02 2510 1
[email protected]

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
[email protected]

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

United Kingdom
(Northern Ireland)
Janssen Sciences Ireland UC
Tel: +44 1 494 567 444
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency https://www.ema.europa.eu.
The following information is intended exclusively for healthcare professionals

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: VELCADE is a cytotoxic agent. Consequently, particular attention must be paid during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF VELCADE.

• 1.1 Preparation of the 3.5 mg vial: carefully add 3.5 mlof sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing VELCADE powder, using an appropriate syringe and 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 colorless with a final pH between 4 and 7. It is not necessary to check the pH of the solution.

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or a change in color. If particulate matter or a change in color is present, the solution must not be used and must be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3 The reconstituted solution is without preservatives 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 for a maximum of 8 hours in the syringe. The total storage time of the reconstituted medicine must not exceed 8 hours before administration. If the reconstituted solution is not used immediately after preparation, it is the user's responsibility to comply with the storage conditions and times of the product before use.

It is not necessary to protect the reconstituted medicine from light.

2. ADMINISTRATION

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

VELCADE 3,5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. Do not administer through other routes. Intrathecal administration has
caused deaths.

3. DISPOSAL

The vial is for single use and any remaining solution must be discarded.
Unused medicine and waste materials 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: VELCADE is a cytotoxic agent. Consequently, particular
attention must be paid during handling and preparation. It is recommended to wear gloves and other
protective clothing to prevent skin contact.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, DURING THE
HANDLING OF VELCADE, ASEPTIC TECHNIQUE RULES MUST BE OBSERVED.

• 1.1 Preparation of the 3.5 mg vial: carefully add 1.4 mlof sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing VELCADE powder, using an appropriate syringe and without removing the vial stopper. The lyophilized powder dissolves completely in less than 2 minutes.

The concentration of the resulting solution is 2.5 mg/ml. The solution will be clear and
colorless with a final pH between 4 and 7. It is not necessary to check the pH of the solution.

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or a color change. If particulate matter or a color change is present, the solution must not be used and must be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered subcutaneously(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 for a maximum of 8 hours in the syringe. The total storage time of the reconstituted medicine must not exceed 8 hours before administration. If the reconstituted solution is not used immediately after preparation, it is the user's responsibility to comply with the storage conditions and times of the product before use.

The reconstituted medicine does not need to be protected from light.

2. ADMINISTRATION

• Once dissolved, withdraw the appropriate amount of the reconstituted solution in accordance with the dose calculated based on the patient's body surface area.
• Confirm the dose and concentration in the syringe before use (check that the syringe is marked for subcutaneous administration).
• Inject the solution subcutaneously, at a 45-90° angle.
• The reconstituted solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left).
• With subsequent administrations, it is necessary to rotate the injection site.
• If local reactions occur at the injection site after subcutaneous injection of VELCADE, a lower concentration of VELCADE 3.5 mg solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

VELCADE 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE ONLY. Do not administer through other routes. Intrathecal administration has
caused deaths.

3. DISPOSAL

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