Velcade 3.5 mg, powder for solution for injection: detailed information

Brand name Velcade 3.5 mg, powder for solution for injection

Form powder for solution for injection

Active substance / Dosage

BORTEZOMIB · 3,5 mg

Prescription type Hospital Use Only

ATC code

L01X L01XG L01XG01

Registration number 04274001

Manufacturer Janssen-Cilag International N.V

Velcade 3.5 mg, powder for solution for injection powder for solution for injection

Table of Contents

Package leaflet: Information for the user
Introduction
1. What VELCADE is and what it is used for
2. What you need to know before using VELCADE
3. How to use VELCADE
4. Possible adverse effects
5. Storage of VELCADE
6. Contents of the pack and other information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

VELCADE 3.5 mg powder for solution for injection

bortezomib

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

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

Contents of this leaflet:

What VELCADE is and what it is used for
What you need to know before using VELCADE
How to use VELCADE
Possible side effects
How to store VELCADE
Contents of the pack and other information

1. What VELCADE is and what it is used for

VELCADE contains the active substance bortezomib, a "proteasome inhibitor". Proteasomes play an important role in regulating cell function and growth. Bortezomib can destroy cancer cells by interfering with their normal function.

VELCADE is used in the treatment of multiple myeloma (a cancer of the bone marrow) in patients over 18 years of age:

alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is progressing after having received at least one prior therapy, and for those patients for whom blood stem cell transplantation has failed or is not suitable;
in combination with melphalan and prednisone, for patients who have not received prior treatment and for whom high-dose chemotherapy followed by blood stem cell transplantation is not suitable;
in combination with dexamethasone or with dexamethasone and thalidomide, for patients who have not received prior treatment and who are undergoing high-dose chemotherapy followed by blood stem cell transplantation (induction treatment).

VELCADE is also used in the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged 18 years or older, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is not considered appropriate.

2. What you need to know before using VELCADE

Do not use VELCADE

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

Warnings and precautions

Tell your doctor if you have any of the following:

low red or white blood cell counts
bleeding problems and/or low platelet count in the blood
diarrhea, constipation, nausea, or vomiting
history of fainting, dizziness, or lightheadedness
kidney problems
moderate to severe liver problems
previous numbness, tingling, or pain in hands or feet (neuropathy)
heart problems or blood pressure issues
difficulty breathing or cough
seizures
shingles (localized, including around the eyes, or widespread)
symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss or changes, and difficulty breathing
memory loss, thinking changes, difficulty walking, or vision loss—these may be signs of a serious brain infection, and your doctor may recommend further testing and monitoring.

You will need to have regular blood tests before and during treatment with VELCADE to monitor your blood cell counts.

Tell your doctor if you have mantle cell lymphoma and are receiving rituximab together with VELCADE:

if you think you currently have or have had hepatitis infection in the past. In some cases, patients who have had hepatitis B may experience reactivation of the infection, which can be fatal. If you have a history of hepatitis B infection, your doctor will closely monitor you for signs of active hepatitis.

Before starting treatment with VELCADE, you should read the package leaflets of all the medicines you are to take in combination with VELCADE to review information related to these medicines.

When thalidomide is used, special attention must be paid to pregnancy testing and preventive measures (see Pregnancy and Breast-feeding in this section).

Children and adolescents

VELCADE should not be used in children and adolescents because it is not known how the medicine will affect them.

Use of VELCADE with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to 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 for depression or other conditions
oral antidiabetic medicines

Pregnancy and breast-feeding

You must not use VELCADE if you are pregnant unless clearly necessary.

Both men and women using VELCADE must use effective contraception during treatment and for up to 3 months after treatment ends. If you become pregnant despite these measures, inform your doctor immediately.

You must not breast-feed while using VELCADE. Consult your doctor about when it is safe to restart breast-feeding after completing your treatment.

Thalidomide causes birth defects and fetal death. When VELCADE is administered in combination with thalidomide, the thalidomide pregnancy prevention program must be followed (refer to the thalidomide package leaflet).

Driving and using machines

VELCADE may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate tools or machinery if you experience these side effects. Even if you do not experience them, you should still remain cautious.

3. How to use VELCADE

Your doctor will determine the dose of VELCADE based on your height and weight (body surface area). The usual starting dose of VELCADE is 1.3 mg/m² of body surface area, administered twice weekly.

Your doctor may adjust the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain adverse effects, and your underlying condition (e.g., liver problems).

Relapsed multiple myeloma

When VELCADE is given alone, you will receive 4 doses of VELCADE 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).

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

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

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

When VELCADE is administered together with dexamethasone, you will receive VELCADE intravenously or subcutaneously in a 21-day treatment cycle, and dexamethasone 20 mg is administered orally 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).

Previously untreated multiple myeloma

If you have not previously been treated for multiple myeloma and are not eligible for a stem cell transplant, you will receive VELCADE in combination with two other medicines: melphalan and prednisone.

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

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

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

If you have not previously received treatment for multiple myeloma and are eligible for a stem cell transplant, you will receive VELCADE intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction therapy.

When VELCADE is administered together with dexamethasone, you will receive VELCADE intravenously or subcutaneously in a 21-day treatment cycle, and 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 VELCADE treatment cycle.

You will receive 4 cycles (12 weeks).

When VELCADE is administered together with thalidomide and dexamethasone, the duration of a 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 orally once daily 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 from the second cycle onwards it may be further increased to 200 mg daily.

You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not previously been treated for mantle cell lymphoma, you will receive VELCADE intravenously or subcutaneously in combination with 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 one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines are administered by intravenous infusion on day 1 of the 21-day VELCADE treatment cycle:

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

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

How VELCADE is administered

This medicine is administered intravenously or subcutaneously. VELCADE will be administered by a healthcare professional experienced in the use of cytotoxic agents.

The VELCADE powder must be dissolved before administration. This will be done by a healthcare professional. The reconstituted solution is then injected into a vein or under the skin. The intravenous injection is rapid, lasting between 3 and 5 seconds. The subcutaneous injection is administered in the thighs or abdomen.

If you receive more VELCADE than you should

This medicine will be administered by your doctor or nurse, so it is unlikely that you will receive too much. In the unlikely event of an overdose, your doctor will monitor you for any adverse effects.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. Some of these effects may be serious.

If you are administered VELCADE for multiple myeloma or mantle cell lymphoma, inform your doctor immediately if you notice any of the following symptoms:

Muscle cramps, muscle weakness
Confusion, loss or changes in vision, blindness, seizures, headaches
Difficulty breathing, swelling of the feet, or changes in heart rhythm, high blood pressure, fatigue, fainting
Cough and difficulty breathing or chest tightness.

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

Platelets, which may make you more prone to bruising (bruises) or bleeding without evident injury (for example, intestinal, stomach, mouth, or gum bleeding, or bleeding in the brain or liver)
Red blood cells, which may 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 administered VELCADE for the treatment of multiple myeloma, the adverse effects you may experience are listed below:

Very common adverse effects (may affect more than 1 in 10 patients)

Tingling, numbness, prickling sensations, or burning sensation in the skin, or pain in 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 bloating (can be severe)
Diarrhea: if this occurs, it is important to drink more fluids than usual. Your doctor may prescribe another medicine to control the diarrhea
Exhaustion (fatigue), feeling of weakness
Muscle pain, bone pain

Common adverse effects (may affect up to 1 in 10 patients)

Low blood pressure, sudden drop in blood pressure when standing, which could lead to fainting
High blood pressure
Decreased kidney function
Headache
General feeling of discomfort, pain, dizziness, lightheadedness, feeling of weakness, or loss of consciousness
Chills
Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness
Herpes zoster (localized, including around the eyes, or widespread across the body)
Chest pain or difficulty breathing during exercise
Various types of rashes
Itchy skin, skin lumps, or dry skin
Facial flushing or broken small capillaries
Redness of the skin
Dehydration
Indigestion, bloating, belching, flatulence, stomach pain, intestinal or stomach bleeding
Liver function abnormalities
Mouth or lip sores, dry mouth, mouth ulcers, or sore throat
Weight loss, loss of taste
Muscle cramps, muscle spasms, muscle weakness, limb pain
Blurred vision
Infection of the outer layer of the eye and inner surface of the eyelids (conjunctivitis)
Nosebleeds
Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation
Swelling of the body, including around the eyes and other body parts

Uncommon adverse effects (may affect up to 1 in 100 patients)

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 disorders
Poor circulation
Inflammation of the heart lining or fluid around the heart
Infections, including urinary tract infections, flu, herpes virus infection, ear infection, and cellulitis
Bloody stools or bleeding from mucous membranes, for example, from the mouth or vagina
Cerebrovascular disorders
Paralysis, seizures, falls, movement disorders, altered or decreased sensitivity (touch, hearing, taste, smell), attention disorders, tremors, jerking movements
Arthritis, including inflammation of joints in fingers, toes, and jaw
Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. These may include difficulty breathing, shortness of breath, breathlessness without exertion, breathing that may become shallow, difficult, or stop, and labored breathing
Hiccups, speech disorders
Increased or decreased urine output (due to kidney injury), painful urination, or blood/protein in urine, fluid retention
Altered level of consciousness, confusion, memory impairment or loss
Hypersensitivity
Hearing loss, deafness, or ringing in the ears (tinnitus), ear discomfort
Hormonal disorders that may affect salt and water absorption
Overactivity of the thyroid gland
Inability to produce enough insulin or resistance to normal insulin levels
Eye irritation or inflammation, excessively wet eyes, eye pain, dry eyes, eye infections, eyelid cyst (chalazion), red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye hemorrhage
Swollen lymph nodes
Joint or muscle stiffness, heaviness sensation, groin pain
Hair loss and abnormal hair texture
Allergic reactions
Redness or pain at the injection site
Mouth pain
Infections or inflammation of the mouth, esophagus, stomach, and intestine, sometimes associated with pain or bleeding, reduced intestinal movement (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood
Skin infections
Bacterial and viral infections
Dental infections
Pancreatitis, bile duct obstruction
Genital pain, difficulty achieving an erection
Weight gain
Thirst
Hepatitis
Injection site reactions or device-related disorders
Skin reactions and disorders (which may be severe and life-threatening), skin ulcers
Bruising, falls, and injuries
Inflammation or hemorrhage of blood vessels appearing as small red or purple spots (usually on the legs) up to large bruise-like areas under the skin or tissue
Benign cysts
A serious, reversible brain disorder including seizures, high blood pressure, headaches, fatigue, confusion, blindness, or other vision problems.

Rare adverse effects (may affect up to 1 in 1,000 patients)

Heart problems, including heart attack, angina
Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)
Flushing
Discoloration of veins
Inflammation of spinal nerves
Ear problems, ear bleeding
Underactivity of the thyroid gland
Budd–Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins)
Changes or abnormalities in intestinal function
Cerebral hemorrhage
Yellowing of the eyes and skin (jaundice)
Severe allergic reaction (anaphylactic shock), symptoms of which may include difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense skin itching or skin lumps, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
Breast disorders
Vaginal tear
Genital inflammation
Inability to tolerate alcohol consumption
Wasting or loss of body mass
Increased appetite
Fistula
Joint effusion
Cysts in the joint lining (synovial cysts)
Fracture
Breakdown of muscle fibers causing other complications
Liver swelling, liver hemorrhage
Kidney cancer
Skin disease resembling psoriasis
Skin cancer
Skin pallor
Increased platelets or plasma cells (a type of white blood cell) in the blood
Blood clots in small blood vessels (thrombotic microangiopathy)
Abnormal reaction to blood transfusions
Partial or complete vision loss
Loss of libido
Drooling
Protruding eyes
Light sensitivity
Rapid breathing
Rectal pain
Gallstones
Hernia
Wounds
Weak or brittle nails
Abnormal protein deposits in vital organs
Coma
Intestinal ulcers
Multi-organ failure
Death

If you are administered VELCADE in combination with other medicines for the treatment of mantle cell lymphoma, the adverse effects you may experience are listed below:

Very common adverse effects (may affect more than 1 in 10 patients)

Pneumonia
Loss of appetite
Tingling, numbness, prickling sensations, or burning sensation in the skin, or pain in hands or feet due to nerve damage
Nausea or vomiting
Diarrhea
Mouth ulcers
Constipation
Muscle pain, bone pain
Hair loss and abnormal hair texture
Exhaustion, feeling of weakness
Fever

Common adverse effects (may affect up to 1 in 10 patients)

Herpes zoster (localized, including around the eyes, or widespread across 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 level of consciousness, confusion
Dizziness
Increased heart rate, high blood pressure, sweating
Abnormal vision, 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 could lead to fainting
Difficulty breathing during exercise
Cough
Hiccups
Ringing in the ears (tinnitus), ear discomfort
Intestinal or stomach bleeding
Indigestion
Stomach pain, bloating
Difficulty swallowing
Infection or inflammation of stomach and intestine
Stomach pain
Mouth or lip sores, sore throat
Liver function abnormalities
Itchy skin
Redness of the skin
Rash
Muscle spasms
Urinary tract infection
Limb pain
Swelling of the body, including around the eyes and other body parts
Chills
Redness and pain at the injection site
General feeling of discomfort
Weight loss
Weight gain

Uncommon adverse effects (may affect up to 1 in 100 patients)

Hepatitis
Severe allergic reaction (anaphylactic reaction), symptoms of which may include difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense skin itching or skin lumps, swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing, collapse
Movement disorders, paralysis, jerking
Dizziness
Hearing loss, deafness
Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. These may include difficulty breathing, shortness of breath, breathlessness without exertion, breathing that may become shallow, difficult, or stop, and labored breathing
Blood clots in the lungs
Yellowing of the eyes and skin (jaundice)
Eyelid cyst (chalazion), red and swollen eyelids

Rare adverse effects (may affect up to 1 in 1,000 patients)

Blood clots in small blood vessels (thrombotic microangiopathy)
Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of VELCADE

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 packaging following EXP.

Do not store above 30°C. Keep the vial in the outer packaging to protect it from light.

The reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions prior to use are the responsibility of the user. However, the reconstituted solution is stable for 8 hours at 25°C when stored in the original vial and/or a syringe; the total storage time of the reconstituted medicine must not exceed 8 hours before administration.

VELCADE is for single use only. Any unused medicine and materials that have come into contact with it should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

Composition of VELCADE

The active substance is bortezomib. Each vial contains 3.5 milligrams of bortezomib (as boric acid ester of mannitol).
The other components are mannitol (E421) and nitrogen.

Reconstitution for intravenous administration:

After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.

Reconstitution for subcutaneous administration:

After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

Appearance of the product and contents of the pack

VELCADE powder for injectable solution is a paste or white to off-white powder.

Each pack of VELCADE 3.5 mg powder for injectable solution contains a 10 ml glass vial with a royal blue cap, in a transparent blister.

Marketing Authorization Holder

JANSSEN-CILAG INTERNATIONAL NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer responsible for manufacturing

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

More information about this medicinal product can be requested by contacting the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium

Janssen-Cilag NV

Tel/Tél + 32 14 64 94 11