Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - velcade

Document Subject

Generated Narrative: MedicinalProductDefinition mp227bd9b21ea0c447e44bb88e14511a9d

identifier: http://ema.europa.eu/identifier/EU/1/04/274/002

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: VELCADE 1 mg powder for solution for injection

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-227bd9b21ea0c447e44bb88e14511a9d

identifier: http://ema.europa.eu/identifier/EU/1/04/274/002

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - velcade

Attesters

What is in 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

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

alone or together with the medicines pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (progressive) after receiving at least one prior treatment and for whom blood stem cell transplantation was not successful or is unsuitable.

in combination with the medicines melphalan and prednisone, for patients whose disease has not been previously treated and are unsuitable for high-dose chemotherapy with blood stem cell transplantation.

in combination with the medicines dexamethasone or dexamethasone together with thalidomide, for patients whose disease has not been previously treated and before receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment). VELCADE is used for the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients 18 years or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is unsuitable.

Do not use VELCADE

if you are allergic to bortezomib, boron or to any of the other ingredients of this medicine (listed in section 6)

if you have certain severe lung or heart problems. Warnings and precautions You should tell your doctor if you have any of the following:

low numbers of red or white blood cells

bleeding problems and/or low number of platelets in your blood

diarrhoea, constipation, nausea or vomiting

fainting, dizziness or light-headedness in the past

kidney problems

moderate to severe liver problems

numbness, tingling, or pain in the hands or feet (neuropathy) in the past

heart or blood pressure problems

shortness of breath or cough

seizures

shingles (localised including around the eyes or spread across the body)

symptoms of tumor lysis syndrome such as muscle cramping, muscle weakness, confusion, visual loss or disturbances and shortness of breath

memory loss, trouble thinking, difficulty with walking or loss of vision. These may be signs of a serious brain infection and your doctor may suggest further testing and follow-up. You will have to take regular blood tests before and during your treatment with VELCADE, to check your blood cell counts regularly. If you have mantle cell lymphoma and are given the medicine rituximab with VELCADE you should tell your doctor:

if you think you have hepatitis infection now or have had it in the past. In a few cases, patients who have had hepatitis B might have a repeated attack of hepatitis, which can be fatal. If you have a history of hepatitis B infection you will be carefully checked by your doctor for signs of active hepatitis B. You must read the package leaflets of all medicinal products to be taken in combination with VELCADE for information related to these medicines before starting treatment with VELCADE. When thalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (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. Other medicines and VELCADE Please 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 for depression or other conditions

oral antidiabetics Pregnancy and breast-feeding You should not use VELCADE if you are pregnant, unless clearly necessary. Both men and women receiving VELCADE must use effective contraception during and for up to 3 months after treatment. If, despite these measures, pregnancy occurs, tell your doctor immediately. You should not breast-feed while using VELCADE. Discuss with your doctor when it is safe to restart breast-feeding after finishing your treatment. Thalidomide causes birth defects and foetal death. When VELCADE is given in combination with thalidomide you must follow the pregnancy prevention programme for thalidomide (see package leaflet for thalidomide). Driving and using machines VELCADE might cause tiredness, dizziness, fainting, or blurred vision. Do not drive or operate tools or machines if you experience such side effects; even if you do not, you should still be cautious.

Your doctor will work out your dose of VELCADE according to your height and weight (body surface area). The usual starting dose of VELCADE is 1.3 mg/m2 body surface area twice a week. Your doctor may change the dose and total number of treatment cycles, depending on your response to the treatment on the occurrence of certain side effects and on your underlying conditions (e.g. liver problems). Progressive multiple myeloma When VELCADE is given alone, you will receive 4 doses of VELCADE intravenously on days 1, 4, 8 and 11, followed by a 10-day rest period without treatment. This 21-day period (3 weeks) corresponds to one treatment cycle. You might receive up to 8 cycles (24 weeks). You may also be given VELCADE together with the medicines pegylated liposomal doxorubicin or dexamethasone. When VELCADE is given together with pegylated liposomal doxorubicin, you will receive VELCADE intravenously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m2 is given on day 4 of the VELCADE 21-day treatment cycle as an intravenous infusion after the VELCADE injection. You might receive up to 8 cycles (24 weeks). When VELCADE is given together with dexamethasone, you will receive VELCADE intravenously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on days 1, 2, 4, 5, 8, 9, 11, and 12, of the VELCADE, 21-day treatment cycle. You might receive up to 8 cycles (24 weeks). Previously untreated multiple myeloma If you have not been treated before for multiple myeloma, and you are not suitable for blood stem cell transplantation you will receive VELCADE intravenously together with two other medicines; 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 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 both given orally on days 1, 2, 3 and 4 of the first week of each cycle. If you have not been treated before for multiple myeloma, and you are suitable for blood stem cell transplantation you will receive VELCADE intravenously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment. When VELCADE is given together with dexamethasone, you will receive VELCADE intravenously as a 21-day treatment cycle and dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the VELCADE 21-day treatment cycle. You will receive 4 cycles (12 weeks). When VELCADE is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks). Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the VELCADE 28-day treatment cycle and thalidomide is given orally daily at 50 mg up to day 14 of the first cycle, and if tolerated the thalidomide dose is increased to 100 mg on days 15-28 and may be further increased to 200 mg daily from the second cycle onwards. You might receive up to 6 cycles (24 weeks). Previously untreated mantle cell lymphoma If you have not been treated before for mantle cell lymphoma you will receive VELCADE intravenously together with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone. VELCADE is given intravenously on days 1, 4, 8 and 11, followed by a rest period without treatment. The duration of a treatment cycle is 21 days (3 weeks). You might receive up to 8 cycles (24 weeks). The following medicinal products are given on day 1 of each VELCADE 21-day treatment cycle as intravenous infusions: Rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2 and doxorubicin at 50 mg/m2. Prednisone is given orally at 100 mg/m2 on days 1, 2, 3, 4 and 5 of the VELCADE treatment cycle. How VELCADE is given This medicine is for intravenous use only. VELCADE will be administered by a health care professional experienced in the use of cytotoxic medicines. VELCADE powder has to be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then injected into a vein rapidly, over 3 to 5 seconds. If you are given too much VELCADE As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too much. In the unlikely event of an overdose, your doctor will monitor you for 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 straight away if you notice any of the following symptoms:

muscle cramping, muscle weakness

confusion, visual loss or disturbances, blindness, seizures, headaches

shortness of breath, swelling of your feet or changes in your heart beat, high blood pressure, tiredness, fainting

coughing and breathing difficulties or tightness in the chest. Treatment with VELCADE can very commonly cause a decrease in the numbers of red and white blood cells and platelets in your blood. Therefore, you will have to take regular blood tests before and during your treatment with VELCADE, to check your blood cell counts regularly. You may experience a reduction in the number of:

platelets, which may make you be more prone to bruising, or to bleeding without obvious injury (e.g., bleeding from your bowels, stomach, mouth and gum or bleeding in the brain or bleeding from the liver)

red blood cells, which can cause anaemia, with symptoms such as tiredness and paleness

white blood cells may make you more prone to infections or flu-like symptoms. If you are given VELCADE for the treatment of multiple myeloma the side effects you may get are listed below: Very common side effects (may affect more than 1 in 10 people)

Sensitivity, 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 bloating (can be severe)

Diarrhoea: if this happens, it is important that you drink more water than usual. Your doctor may give you another medicine to control diarrhoea

Tiredness (fatigue), feeling weak

Muscle pain, bone pain Common side effects (may affect up to 1 in 10 people)

Low blood pressure, sudden fall of blood pressure on standing which may lead to fainting

High blood pressure

Reduced functioning of your kidneys

Headache

General ill feeling, pain, vertigo, light-headedness, a feeling of weakness or loss of consciousness

Shivering

Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, coughing with phlegm, flu like illness

Shingles (localised including around the eyes or spread across the body)

Chest pains or shortness of breath with exercise

Different types of rash

Itching of the skin, lumps on the skin or dry skin

Facial blushing or tiny broken capillaries

Redness of the skin

Dehydration

Heartburn, bloating, belching, wind, stomach pain, bleeding from your bowels or stomach

Alteration of liver functioning

A sore mouth or lip, dry mouth, mouth ulcers or throat pain

Weight loss, loss of taste

Muscle cramps, muscle spasms, muscle weakness, pain in your limbs

Blurred vision

Infection of the outermost layer of the eye and the inner surface of the eyelids (conjunctivitis)

Nose bleeds

Difficulty or problems in sleeping, sweating, anxiety, mood swings, depressed mood, restlessness or agitation, changes in your mental status, disorientation

Swelling of body, to include around 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 reduced heart rate

Failing of your kidneys

Inflammation of a vein, blood clots in your veins and lungs

Problems with blood clotting

Insufficient circulation

Inflammation of the lining around your heart or fluid around your heart

Infections including urinary tract infections, the flu, herpes virus infections, ear infection and cellulitis

Bloody stools, or bleeding from mucosal membranes, e.g., mouth, vagina

Cerebrovascular disorders

Paralysis, seizures, falling, movement disorders, abnormal or change in, or reduced sensation (feeling, hearing, tasting, smelling), attention disturbance, trembling, twitching

Arthritis, including inflammation of the joints in the fingers, toes, and the jaw

Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing

Hiccups, speech disorders

Increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins 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

Hormone abnormality which may affect salt and water absorption

Overactive thyroid gland

Inability to produce enough insulin or resistance to normal levels of insulin

Irritated or inflamed eyes, excessively wet eyes, painful eyes, dry eyes, eye infections, lump in the eyelid (chalazion), red and swollen eyelids, discharge from the eyes, abnormal vision, bleeding of the eye

Swelling of your lymph glands

Joint or muscle stiffness, sense of heaviness, pain in your groin

Hair loss and abnormal hair texture

Allergic reactions

Redness or pain at the injection site

Mouth pain

Infections or inflammation of the mouth, mouth ulcers, oesophagus, stomach and intestines, sometimes associated with pain or bleeding, poor movement of the intestines (including blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting of blood

Skin infections

Bacterial and viral infections

Tooth infection

Inflammation of the pancreas, obstruction of the bile duct

Genital pain, problem having an erection

Weight increase

Thirst

Hepatitis

Injection site or injection device related disorders

Skin reactions and disorders (which may be severe and life threatening), skin ulcers

Bruises, falls and injuries

Inflammation or haemorrhage of the blood vessels that can appear as small red or purple dots (usually on the legs) to large bruise-like patches under the skin or tissue

Benign cysts

A severe reversible brain condition which includes seizures, high blood pressure, headaches, tiredness, confusion, blindness or other vision problems. Rare side effects (may affect up to 1 in 1,000 people)

Heart problems to include heart attack, angina

Serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barr
syndrome)

Flushing

Discoloration of the veins

Inflammation of the spinal nerve

Problems with your ear, bleeding from your ear

Underactivity of your thyroid gland

Budd Chiari syndrome (the clinical symptoms caused by blockage of the hepatic veins)

Changes in or abnormal bowel function

Bleeding in the brain

Yellow discolouration of eyes and skin (jaundice)

Serious allergic reaction (anaphylactic shock) signs of which may include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse

Breast disorders

Vaginal tears

Genital swelling

Inability to tolerate alcohol consumption

Wasting, or loss of body mass

Increased appetite

Fistula

Joint effusion

Cysts in the lining of joints (synovial cysts)

Fracture

Breakdown of muscle fibers leading to other complications

Swelling of the liver, bleeding from the liver

Cancer of the kidney

Psoriasis like skin condition

Cancer of the skin

Paleness of the skin

Increase of platelets or plasma cells (a type of white cell) in the blood

Blood clot in small blood vessels (thrombotic microangiopathy)

Abnormal reaction to blood transfusions

Partial or total loss of vision

Decreased sex drive

Drooling

Bulging eyes

Sensitivity to light

Rapid breathing

Rectal pain

Gallstones

Hernia

Injuries

Brittle or weak nails

Abnormal protein deposits in your vital organs

Coma

Intestinal ulcers

Multi-organ failure

Death If you are given VELCADE together with other medicines for the treatment of mantle cell lymphoma the side effects you may get are listed below: Very common side effects (may affect more than 1 in 10 people)

Pneumonia

Loss of appetite

Sensitivity, 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 and abnormal hair texture

Tiredness, feeling weak

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

Shingles (localized including around the eyes or spread across the body)

Herpes virus infections

Bacterial and viral infections

Respiratory infections, bronchitis, coughing with phlegm, 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 in sleeping

Loss of conciousness

Altered level of consciousness, confusion

Feeling dizzy

Increased heartbeat, high blood pressure, sweating,

Abnormal vision, blurred vision

Heart failure, heart attack, chest pain, chest discomfort, increased or reduced heart rate

High or low blood pressure

Sudden fall of blood pressure upon standing which may lead to fainting

Shortness of breath with exercise

Cough

Hiccups

Ringing in the ears, ear discomfort

Bleeding from your bowels or stomach

Heartburn

Stomach pain, bloating

Difficulty swallowing

Infection or inflammation of the stomach and intentines

Stomach pain

Sore mouth or lip, throat pain

Alteration of liver function

Itching of skin

Redness of skin

Rash

Muscle spasms

Infection of the urinary tract

Pain in limbs

Swelling of body, to include eyes and other parts of the body

Shivering

Redness and pain at injection site

General ill feeling

Weight loss

Weight increase 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 chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse

Movement disorders, paralysis, twitching

Vertigo

Hearing loss, deafness

Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing

Blood clots in your lungs

Yellow discoloration of the eyes and skin (jaundice)

Lump in the eyelid (chalazion), red and swollen eyelids Rare side effects (may affect up to 1 in 1,000 people)

Blood clot in small blood vessels (thrombotic microangiopathy)

Serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barr
syndrome) Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 carton after EXP. Do not store above 30 C. Keep the vial in the outer carton in order to protect from light. The reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. However, the reconstituted solution is stable for 8 hours at 25 C stored in the original vial and/or a syringe, with a total storage time for the reconstituted medicine not exceeding 8 hours prior to administration. VELCADE is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

What VELCADE contains

The active substance is bortezomib. Each vial contains 1 mg of bortezomib (as a mannitol boronic ester). After reconstitution, 1 ml of solution for injection contains 1 mg bortezomib.

The other ingredients are mannitol (E421) and nitrogen. What VELCADE looks like and contents of the pack VELCADE powder for solution for injection is a white to off-white cake or powder. Each carton of VELCADE 1 mg powder for solution for injection contains a glass vial with a green cap, in a transparent blister pack. Marketing Authorisation Holder JANSSEN-CILAG INTERNATIONAL NV Turnhoutseweg B-2340 Beerse Belgium Manufacturer Janssen Pharmaceutica NV Turnhoutseweg B-2340 Beerse Belgium For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder. Belgi /Belgique/Belgien Janssen-Cilag NV Tel/T l + 32 14 64 94 janssen@jacbe.jnj.com Lietuva UAB "JOHNSON & JOHNSON" Tel: +370 5 278 68 lt@its.jnj.com

&
.: +359 2 489 94 jjsafety@its.jnj.com Luxembourg/Luxemburg Janssen-Cilag NV T l/Tel: + 32 14 64 94 janssen@jacbe.jnj.com esk republika Janssen-Cilag s.r.o. Tel: +420 227 012 Magyarorsz g Janssen-Cilag Kft. Tel.: +36 1 884 2janssenhu@its.jnj.com Danmark Janssen-Cilag A/S Tlf: +45 4594 8jacdk@its.jnj.com Malta AM MANGION LTD. Tel: +356 2397 6Deutschland Janssen-Cilag GmbH Tel: +49 2137 955 jancil@its.jnj.com Nederland Janssen-Cilag B.V. Tel: + 31 76 711 1janssen@jacnl.jnj.com Eesti UAB "JOHNSON & JOHNSON" Eesti filiaal Tel: +372 617 7ee@its.jnj.com Norge Janssen-Cilag AS Tlf: + 47 24 12 65 jacno@its.jnj.com

Janssen-Cilag . . . . T : +30 210 80 90 sterreich Janssen-Cilag Pharma GmbH Tel:+43 1 610 Espa a Janssen-Cilag, S.A. Tel: +34 91 722 81 contacto@its.jnj.com Polska Janssen-Cilag Polska Sp. z o.o. Tel.: + 48 22 237 60 France Janssen-Cilag T l: 0 800 25 50 75 / + 33 1 55 00 40 medisource@its.jnj.com Portugal Janssen-Cilag Farmac utica, Lda. Tel: +351 214 368 Hrvatska Johnson & Johnson S.E. d.o.o. Tel: +385 1 6610 jjsafety@JNJCR.JNJ.com Rom nia Johnson & Johnson Rom nia SRL Tel: +40 21 207 1Ireland Janssen Sciences Ireland UC Tel: +353 1 800 709 Slovenija Johnson & Johnson d.o.o. Tel. +386 1 401 18 Janssen_safety_slo@its.jnj.com sland Janssen-Cilag AB c/o Vistor hf. S mi: +354 535 7janssen@vistor.is Slovensk republika Johnson & Johnson s.r.o. Tel: +421 232 408 Italia Janssen-Cilag SpA Tel: 800.688.777 / +39 02 2510 1 janssenita@its.jnj.com Suomi/Finland Janssen-Cilag Oy Puh/Tel: +358 207 531 jacfi@its.jnj.com

: +357 22 207 Sverige Janssen-Cilag AB Tel: +46 8 626 50 jacse@its.jnj.com Latvija UAB "JOHNSON & JOHNSON" fili le Latvij Tel: +371 678 93lv@its.jnj.com United Kingdom (Northern Ireland) Janssen Sciences Ireland UC Tel: +44 1 494 567 This leaflet was last revised in Detailed information on this medicine is available on the website of the European Medicines Agency