VEGZELMA 25 mg /Ml Koncentrat Do Roztworu Infuzyjnego

Treść ulotki

1. VEGZELMA 25 mg/mL concentrate for solution for infusion
   1. What is VEGZELMA and what is it used for
   2. What you need to know before you use VEGZELMA
   3. How to use VEGZELMA
   4. Possible side effects
   5. How to store VEGZELMA
   6. Contents of the pack and other information

VEGZELMA 25 mg/mL concentrate for solution for infusion

bevacizumab

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

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, pharmacist or nurse.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4

Contents of this leaflet:

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

1. What is VEGZELMA and what is it used for

VEGZELMA contains the active substance bevacizumab, a humanized monoclonal antibody (a type
of protein that is normally produced by the immune system to help the body
defend itself from infection and cancer). Bevacizumab selectively binds to a protein called
“vascular endothelial growth factor” (VEGF), which is present on the lining of the body’s blood
and lymphatic vessels. The VEGF protein causes the growth of blood vessels
within the tumor; these blood vessels supply the tumor with nutrients and oxygen. Once
bevacizumab binds to VEGF, tumor growth is prevented by blocking the development of the blood
vessels that supply nutrients and oxygen to the tumor.
VEGZELMA is a medicine used for the treatment of adult patients with advanced carcinoma
of the colon or rectum. VEGZELMA will be administered in
association with a chemotherapeutic treatment based on fluoropyrimidines.
VEGZELMA is also used for the treatment of adult patients with metastatic
breast cancer. In patients with this type of tumor it will be administered with a
chemotherapeutic regimen based on paclitaxel or capecitabine.
VEGZELMA is also used for the treatment of adult patients with advanced non-small cell lung cancer. VEGZELMA will be administered together with a chemotherapeutic regimen based on
platinum.
VEGZELMA is also used for the treatment of adult patients with advanced non-small cell lung cancer when the tumor cells present certain mutations of a protein
called epidermal growth factor receptor (EGFR). VEGZELMA will be administered in
association with erlotinib.
VEGZELMA is also used for the treatment of adult patients with advanced renal carcinoma. In patients with this type of tumor bevacizumab will be administered with another type of
medicine called interferon.
VEGZELMA is used also for the treatment of adult patients affected by epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in advanced stage. In
patients with these types of tumors bevacizumab will be administered in association with carboplatin and
paclitaxel.
VEGZELMA will be administered in association with carboplatin and gemcitabine or with carboplatin and
paclitaxel when used in adult patients with epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in advanced stage whose disease has recurred at least
6 months after the last time they were treated with a chemotherapeutic regimen containing a
platinum-based agent.
VEGZELMA will be administered in association with paclitaxel, topotecan or liposomal doxorubicin
pegylated when used in adult patients affected by epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in advanced stage whose disease has recurred
within 6 months from the last time they were treated with a chemotherapeutic regimen containing a
platinum-based agent.
VEGZELMA is also used for the treatment of adult patients affected by persistent, recurrent or metastatic cervical cancer. VEGZELMA will be administered in association with paclitaxel
and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot undergo
platinum-based therapy.

2. What you need to know before you use VEGZELMA

Do not use VEGZELMA

• if you are allergic (hypersensitive) to bevacizumab or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic (hypersensitive) to products derived from Chinese hamster ovary (CHO) cells or to other recombinant humanized or human antibodies.
• if you are pregnant.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using VEGZELMA

• VEGZELMA may increase the risk of developing perforations in the intestinal wall. If you have conditions that cause inflammation in the abdomen (e.g. diverticulitis, gastric ulcers, chemotherapy-associated colitis), discuss this with your doctor.
• VEGZELMA may increase the risk of developing an abnormal connection or passage between two organs or vessels. The presence of persistent, recurrent or metastatic cervical carcinoma may determine an increased risk of developing connections between the vagina and any section of the gastrointestinal tract.
• VEGZELMA may increase the risk of bleeding or increase the risk of problems with wound healing after surgery. If you are to undergo surgery, if you have had major surgery in the last 28 days or if you have a surgical wound that has not yet healed, you should not take this medicine.
• VEGZELMA may increase the risk of developing severe skin infections or infections in deeper layers under the skin, especially if you have perforations in the intestinal wall or have problems with wound healing.
• VEGZELMA may increase the incidence of high blood pressure. If you suffer from high blood pressure that is not well controlled with blood pressure medications, discuss this with your doctor. It is important to ensure that your blood pressure is under control before starting treatment with VEGZELMA.
• If you have or have had an aneurysm (dilation and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• VEGZELMA increases the risk of having protein in the urine, especially if you already suffer from high blood pressure.
• The risk of developing blood clots in the arteries (a type of blood vessel) may increase if you are over 65 years of age, if you have diabetes and if you have had previous blood clots in the arteries. Talk to your doctor because blood clots can lead to heart attacks and strokes.
• VEGZELMA may also increase the risk of developing blood clots in the veins (a type of blood vessel).
• VEGZELMA may cause bleeding, in particular bleeding related to the tumor. Consult your doctor if you or other family members tend to suffer from coagulation problems or if you are taking medications to thin the blood for any reason.
• VEGZELMA may cause bleeding inside the brain and around the brain. Consult your doctor if you have a metastatic tumor that affects the brain.
• VEGZELMA may increase the risk of bleeding in the lungs, including blood in your cough or saliva. Discuss with your doctor if you have noticed these events in the past.
• VEGZELMA may increase the risk of developing heart failure. It is important that your doctor knows if you have previously undergone anthracycline therapy (e.g. doxorubicin, a particular type of chemotherapy used to treat some cancers) or thoracic radiotherapy, or if you have heart disease.
• VEGZELMA may cause infections and a reduction in the number of neutrophils (a type of blood cell important for protection against bacteria).
• VEGZELMA may cause hypersensitivity (including anaphylactic shock) and/or infusion reactions (reactions related to the injection of the medicine). Tell your doctor, pharmacist or nurse if you have already had problems after injections, such as dizziness/feeling faint, shortness of breath, swelling or skin rashes.
• A rare neurological adverse effect called reversible posterior encephalopathy syndrome (PRES) has been associated with treatment with VEGZELMA. If you have headache, vision disturbances, confusion or seizures with or without increased pressure, contact your doctor.

Also consult your doctor if the above has occurred in the past.
Before starting treatment with VEGZELMA or during treatment with VEGZELMA:

• if you have had or have pain in the mouth, teeth and/or jaw/mandible, or swelling or inflammation in the mouth, or numbness or heaviness in the jaw/mandible, or have lost a tooth, report it immediately to your doctor and dentist;
• if you are to undergo invasive dental treatment or dental surgery, tell your dentist that you are being treated with VEGZELMA, especially if you have received or are receiving a bisphosphonate injection into the bloodstream.

Your doctor or dentist may suggest that you have a dental check-up before starting treatment
with VEGZELMA.

Children and adolescents
Therapy with VEGZELMA is not recommended in children and adolescents under the age of 18
years as neither safety nor benefits have been established in this patient population.
Bone tissue death (osteonecrosis) in bones other than the jaw has been found in patients
under the age of 18 treated with bevacizumab.

Other medicines and VEGZELMA
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might
take any other medicines.
Combinations of VEGZELMA with another medicine, called sunitinib malate (prescribed for
renal and gastrointestinal tumors), may cause serious side effects. Discuss this with your doctor to
ensure you do not combine these medicines.
Tell your doctor if you are using platinum-based or taxane therapies for metastatic lung or
breast cancer. These therapies in combination with VEGZELMA may increase the risk
of serious side effects.
Tell your doctor if you have recently received or are receiving radiotherapy.

Pregnancy, breastfeeding and fertility
If you are pregnant, you must not use this medicine. VEGZELMA may harm the
unborn child, as it may interrupt the formation of new blood vessels. Your doctor
will advise you to use adequate contraceptive measures during therapy with VEGZELMA
and for at least 6 months after taking the last dose of VEGZELMA.
If you are pregnant, if you suspect you are pregnant during treatment with this medicine
or are planning a pregnancy in the near future, tell your doctor immediately.
You must not breastfeed during treatment with VEGZELMA and for at least
6 months after taking the last dose of VEGZELMA, as this medicine may interfere
with the growth and development of the baby.
VEGZELMA may reduce female fertility. Consult your doctor for further information.
Ask your doctor, pharmacist or nurse before taking any medicine.

Driving and using machines
VEGZELMA has not been shown to reduce the ability to drive vehicles or use tools or
machinery. However, drowsiness and fainting have been reported with the use of VEGZELMA. If
you experience symptoms affecting your vision or concentration, or your ability to react, do
not drive vehicles and do not use machinery until the symptoms have disappeared.

Important information about some ingredients of VEGZELMA
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. essentially
‘sodium-free’.

3. How to use VEGZELMA

Dosage and frequency of administration
The dose of VEGZELMA needed depends on your body weight and the type of cancer that needs to be
treated. The recommended dose is 5 mg, 7.5 mg, 10 mg or 15 mg per kilogram of body weight. Your
doctor will prescribe VEGZELMA at the appropriate dose for you. Treatment with VEGZELMA will be
administered once every 2 or 3 weeks. The number of infusions you will receive will depend on your
response to treatment; however, you should continue to receive this treatment until VEGZELMA is no
longer able to block the growth of your cancer. Your doctor will discuss this with you.

Method and route of administration
VEGZELMA is a concentrate for infusion solution. Depending on the dose prescribed, a portion of the
contents of the vial or the entire vial of VEGZELMA will be diluted with sodium chloride solution before
use. Your doctor or nurse will administer this diluted solution of VEGZELMA with an intravenous
infusion (an IV drip into a vein). The first infusion will be administered over 90 minutes. If this is well
tolerated, the second infusion may be administered over 60 minutes. Subsequent infusions may be
administered over 30 minutes.

Administration of VEGZELMA must be temporarily interrupted

• if severe high blood pressure problems occur, requiring treatment with medications to control blood pressure,
• if you have problems with wound healing after surgery,
• if you are to undergo surgery.

Administration of VEGZELMA must be permanently interrupted if one of the following problems occurs

• severe high blood pressure that cannot be controlled with antihypertensive drugs, or a sudden and severe increase in blood pressure,
• presence of protein in the urine associated with edema (swelling of the body),
• perforation of the intestinal wall,
• an abnormal connection or passage between the trachea and esophagus, internal organs and skin, vagina and any section of the gastrointestinal tract, or between other tissues that are not normally connected (fistula), and which are considered severe by the doctor,
• severe infections of the skin or deeper layers under the skin,
• blood clots in the arteries,
• blood clots in the pulmonary blood vessels,
• severe bleeding of any kind.

If an overdose of VEGZELMA is administered

• You may experience a severe migraine. In this case, seek immediate medical attention from your doctor, pharmacist or nurse.

If you forget to take a dose of VEGZELMA

• The doctor will decide the most appropriate time to administer the next dose of VEGZELMA. Discuss this with your doctor.

If you stop treatment with VEGZELMA
Stopping treatment with VEGZELMA may stop the action of containing tumor growth.
Do not stop treatment with VEGZELMA before talking to your doctor.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you get any side effect, even if not listed in this leaflet, tell your doctor, pharmacist or nurse.
The side effects listed below have been observed in patients treated with VEGZELMA associated with chemotherapy. This does not mean that these side effects were necessarily caused by VEGZELMA.

Allergic reactions
If you should have an allergic reaction, tell your doctor or a member of medical staff immediately. The signs may include: difficulty breathing or chest pain. Redness of the skin or flushing or rash, chills and shivering, feeling unwell (nausea) or vomiting, swelling, dizziness, fast heartbeat and loss of consciousness may also occur.

If you should experience any of the side effects described below, seek immediate medical help.
Serious side effects, which can be very common(may affect more than 1 in

• 10) ,include:
• high blood pressure,
• feeling of numbness or tingling in the hands or feet,
• reduced number of blood cells, including white blood cells, which fight infections (this may be accompanied by fever), and cells that help the blood to clot,
• feeling weak and lacking energy,
• fatigue,
• diarrhoea, nausea, vomiting and abdominal pain.

Serious side effects, which can be common(may affect up to 1 in 10 people), include:

• intestinal perforation,
• bleeding, including bleeding in the lungs in patients with non-small cell lung cancer,
• arteries blocked by a blood clot,
• veins blocked by a blood clot,
• pulmonary blood vessels blocked by a blood clot,
• leg veins blocked by a blood clot,
• heart failure,
• problems with wound healing after surgery,
• redness, peeling, soreness, pain or blistering on the fingers or toes,
• reduced number of red blood cells,
• lack of energy,
• stomach and intestinal disorders,
• muscle and joint pain, muscle weakness,
• dry mouth associated with thirst and/or reduced or dark urine,
• inflammation of the mucous membranes of the mouth, intestines, lungs and airways, reproductive and urinary systems,
• ulcers in the mouth and esophagus that can cause pain and difficulty swallowing,
• pain, including headache, back pain and pain in the pelvic area and anus,
• localized abscesses,
• infection, and in particular blood or bladder infection,
• reduced blood flow to the brain or stroke,
• drowsiness,
• nosebleed,
• increased heart rate (pulse),
• bowel obstruction,
• changes in urine tests (presence of protein in the urine),
• shortness of breath or reduced oxygen levels in the blood,
• skin or deep tissue infections,
• fistulas: abnormal tubular connection between internal organs and skin or other tissues that are not normally connected, including connections between the vagina and gastrointestinal tract in patients with cervical cancer,
• allergic reactions (signs may include difficulty breathing, facial flushing, rash, low or high blood pressure, low oxygen levels in the blood, chest pain, or nausea/vomiting).

Serious side effects of rarefrequency (may affect up to 1 in 1000 people) include:

• sudden, severe allergic reaction with difficulty breathing, swelling, dizziness, fast heartbeat, sweating and loss of consciousness (anaphylactic shock).

Serious side effects of unknownfrequency (frequency cannot be estimated on the basis of the available data) include:

• serious skin or deep tissue infections, especially if you have had perforations in the intestinal wall or problems with wound healing,
• a negative effect on women’s ability to have children (see sections below the list of side effects for further recommendations),
• a condition of the brain with symptoms such as seizures (convulsions), headache, confusion and changes in vision (reversible posterior encephalopathy syndrome (PRES)),
• symptoms suggesting changes in normal brain function (headache, visual disturbances, confusion or convulsions) and high blood pressure,
• dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections),
• blockage of a small vessel(s) in the kidney,
• abnormally high blood pressure in the vessels of the lungs that makes the right side of the heart work harder than normal,
• perforation of the cartilage separating the nostrils,
• perforation of the stomach or intestine,
• an open wound or perforation in the lining of the stomach or small intestine (signs may include abdominal pain, feeling of bloating, tarry black stools, blood in the stools or blood in the vomit),
• bleeding from the lower part of the large intestine,
• gum injuries, with exposure of jaw/jawbone that does not heal, which may be associated with pain and inflammation of the surrounding tissue (see sections below the list of side effects for further recommendations),
• perforation of the gallbladder (symptoms and signs may include abdominal pain, fever and nausea/vomiting).

If you should experience any of the side effects described below, seek help as soon as possible.
Very commonside effects (may affect more than 1 in 10 people), which have not been serious, include:

• constipation,
• loss of appetite,
• fever,
• eye problems (including increased tearing),
• changes in speech,
• changes in taste,
• runny nose,
• dry skin, peeling and inflammation of the skin, change in skin color,
• weight loss,
• nosebleed.

Commonside effects (may affect up to 1 in 10 people), which have not been serious, include:

• changes in voice and hoarseness.

Patients over 65 years of age have a higher risk of experiencing the following side effects:

• blood clots in the arteries, which can lead to stroke or heart attack,
• reduced number of white blood cells and cells that help the blood to clot,
• diarrhoea,
• feeling unwell,
• headache,
• feeling tired,
• high blood pressure.

VEGZELMA can also cause changes in the results of laboratory tests prescribed by your doctor. These include: a reduction in the number of white blood cells, in particular neutrophils (a type of white blood cell that helps protect against infections) in the blood, presence of protein in the urine, reduced potassium, sodium or phosphorus (a mineral) in the blood, increased blood sugar, increased alkaline phosphatase (an enzyme) in the blood; increased serum creatinine (a protein measured through blood tests to assess how your kidneys are functioning); reduced hemoglobin (found in red blood cells and carries oxygen), which may be severe.
Pain in the mouth, teeth and/or jaw/jawbone, swelling or blisters in the mouth, numbness or heaviness in the jaw/jawbone or loss of a tooth. These may be signs and symptoms of damage to the jaw/jawbone (osteonecrosis). Tell your doctor and dentist immediately if you experience any of these effects.
Premenopausal women (women who have a menstrual cycle) may notice irregularities in their menstrual cycles, absence of menstruation and may have negative consequences on fertility. If you are considering becoming pregnant, you should discuss this with your doctor before starting treatment.
VEGZELMA has been developed and manufactured for the treatment of cancer by intravenous injection. It has not been developed or manufactured for administration by injection into the eye. Therefore, the use of this route of administration is not authorized. When bevacizumab is injected directly into the eye (off-label use), the following side effects may occur:

• infection or inflammation of the eyeball,
• redness of the eye, appearance of particles or floating spots in the field of vision ("floaters"), eye pain,
• flashes of light and "floaters" progressing to loss of part of the visual field,
• increased pressure in the eye,
• bleeding in the eye.

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store VEGZELMA

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 outer packaging and
on the vial label after the abbreviation “Scad./EXP”. The expiry date refers to
the last day of that month.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Infusion solutions must be used immediately after they have been diluted. If
immediate use is not possible, the user shall be responsible for the storage times and
conditions, which should normally not exceed 24 hours at a temperature
between 2°C and 8°C, unless the infusion solutions have been prepared in a
sterile environment. If dilution has occurred in a sterile environment, VEGZELMA is stable for 60
days at a temperature between 2°C and 8°C plus an additional 7 days at a temperature between 2°C and 30°C.
Do not use VEGZELMA if you notice particulate matter or colour changes before
administration.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What VEGZELMA contains

• The active substance is bevacizumab.

Each mL of concentrate contains 25 mg of bevacizumab, corresponding to 1.4-16.5 mg/mL
when diluted as recommended.
Each 4 mL vial contains 100 mg of bevacizumab, corresponding to 1.4 mg/mL when
diluted as recommended.
Each 16 mL vial contains 400 mg of bevacizumab, corresponding to 16.5 mg/mL
when diluted as recommended.

• The other ingredients are trehalose dihydrate, sodium phosphate, polysorbate 20 and water for injections.

Description of the appearance of VEGZELMA and contents of the pack
VEGZELMA is a concentrate for solution for infusion. The concentrate is a clear liquid, from
colourless to light brown in a glass vial closed with a rubber stopper. Each vial
contains 100 mg of bevacizumab in 4 mL of solution or 400 mg of bevacizumab in 16 mL of
solution. Each pack of VEGZELMA contains 1 vial, 2 vials or 10 vials.

Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan GmbH
Wegenerstraße 13
89231 Neu Ulm
Germany
Nuvisan France SARL
2400, Route des Colles
06410, Sophia Antipolis
France
Kymos S.L.
Ronda Can Fatjó 7B
(Parc Tecnològic del Vallès) Cerdanyola del Vallès
08290 Barcelona
Spain
Midas Pharma GmbH
Rheinstraße 49
55218 Ingelheim am Rhein
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Celltrion Healthcare Belgium BVBA
Tél/Tel: + 32 1528 7418

Lietuva
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

България
Celltrion Healthcare Hungary Kft.
Тел.: +36 1 231 0493

Luxembourg/Luxemburg
Celltrion Healthcare Belgium BVBA
Tél/Tel: + 32 1528 7418

Česká republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Magyarország
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

Danmark
Celltrion Healthcare Denmark ApS
Tlf: +45 3535 2989
[email protected]

Malta
Mint Health Ltd.
Tel: +356 2093 9800

Deutschland
Celltrion Healthcare Deutschland GmbH
Tel: +49 (0)30 346494150
[email protected]

Nederland
Celltrion Healthcare Netherlands B.V.
Tel: + 31 20 888 7300

Eesti
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Norge
Celltrion Healthcare Norway AS
[email protected]

España
CELLTRION FARMACEUTICA (ESPAÑA)
S.L.
Tel: +34 910 498 478

Ö sterreich
Astro-Pharma GmbH
Tel: +43 1 97 99 860

Ελλάδα
ΒΙΑΝΕΞ Α.Ε.
Τηλ: +30 210 8009111 - 120

Polska
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

France
CELLTRION HEALTHCARE FRANCE SAS
Tél.: +33 (0)1 71 25 27 00

Portugal
CELLTRION PORTUGAL, UNIPESSOAL
LDA
Tel: +351 21 936 8542

Hrvatska
Oktal Pharma d.o.o.
Tel: +385 1 6595 777

România
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Ireland
Celltrion Healthcare Ireland Limited
Tel: +353 1 223 4026

Slovenija
OPH Oktal Pharma d.o.o.
Tel.: +386 1 519 29 22

Ísland
Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493

Slovenská republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Italia
Celltrion Healthcare Italy S.R.L.
Tel: +39 0247927040

Suomi/Finland
Celltrion Healthcare Finland Oy.
Puh/Tel: +358 29 170 7755

Κύπρος
C.A. Papaellinas Ltd
Τηλ: +357 22741741

Sverige
Celltrion Sweden AB
[email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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