Aybintio

Package leaflet: Information for the user

Aybintio 25 mg/mL concentrate for solution for infusion

bevacizumab
Please 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Aybintio is and what it is used for

Aybintio contains the active substance bevacizumab, a humanized monoclonal antibody (a type of protein normally produced by the immune system to help the body defend itself against infection and cancer). Bevacizumab binds selectively to a protein called "vascular endothelial growth factor human" (VEGF), which is present on the lining of blood and lymphatic vessels in the body. The VEGF protein promotes the growth of blood vessels within the tumour; these blood vessels supply nutrients and oxygen to the tumour. Once bevacizumab binds to VEGF, tumour growth is inhibited because the development of blood vessels supplying nutrients and oxygen to the tumour is blocked.

Aybintio is a medicine used to treat adult patients with advanced colorectal cancer, i.e. cancer of the colon or rectum. Aybintio will be administered in combination with a fluoropyrimidine-based chemotherapy regimen.

Aybintio is also used to treat adult patients with metastatic breast cancer. In patients with this type of cancer, Aybintio will be administered with a chemotherapy regimen based on paclitaxel or capecitabine.

Aybintio is also used to treat adult patients with advanced non-small cell lung cancer. Aybintio will be administered together with a platinum-based chemotherapy regimen.

Aybintio is furthermore used to treat adult patients with advanced non-small cell lung cancer when tumour cells have specific mutations in a protein called epidermal growth factor receptor (EGFR). Aybintio will be administered in combination with erlotinib.

Aybintio is also used to treat adult patients with advanced renal cell cancer. In patients with this type of cancer, Aybintio will be administered in combination with another medicine called interferon.

Aybintio is also used to treat adult women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer. In patients with these types of cancer, Aybintio will be administered in combination with carboplatin and paclitaxel.

Aybintio will be administered in combination with carboplatin and gemcitabine or with carboplatin and paclitaxel when used in adult women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer whose disease has recurred at least 6 months after the last time they were treated with a platinum-containing chemotherapy regimen.

Aybintio will be administered in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin when used in adult women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer whose disease has recurred within 6 months of the last time they were treated with a platinum-containing chemotherapy regimen.

Aybintio is also used to treat adult women with persistent, recurrent or metastatic cervical cancer. Aybintio will be administered in combination with paclitaxel and cisplatin or, alternatively, with paclitaxel and topotecan in women who cannot receive platinum-based therapy.

2. What you should know before using Aybintio

Do not use Aybintio

• 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 human or humanized antibodies
• if you are pregnant.

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

• Aybintio may increase the risk of developing intestinal wall perforations. If you have conditions causing abdominal inflammation (e.g., diverticulitis, gastric ulcers, chemotherapy-associated colitis), discuss this with your doctor;
• Aybintio may increase the risk of developing abnormal connections or passages between two organs or vessels. Persistent, recurrent, or metastatic cervical cancer may increase the risk of developing connections between the vagina and any part of the gastrointestinal tract;
• this medicine may increase the risk of bleeding or cause problems with wound healing after surgery. If you are scheduled for surgery, if you have undergone major surgery within the last 28 days, or if you have a surgical wound that has not yet healed, you must not take this medicine;
• Aybintio may increase the risk of developing severe skin infections or infections in deeper layers beneath the skin, especially if you have intestinal wall perforations or problems with wound healing;
• Aybintio may increase the incidence of high blood pressure. If you have high blood pressure that is not well controlled with antihypertensive medications, discuss this with your doctor. It is important to ensure your blood pressure is under control before starting treatment with Aybintio;
• if you have or have had an aneurysm (dilation and weakening of a blood vessel wall) or a tear in the wall of a blood vessel;
• this medicine increases the risk of having protein in the urine, especially if you already have high blood pressure;
• the risk of developing blood clots in arteries (a type of blood vessel) may increase if you are over 65 years of age, have diabetes, or have a history of previous arterial blood clots. Talk to your doctor, as blood clots can lead to heart attacks and strokes;
• Aybintio may also increase the risk of developing blood clots in veins (a type of blood vessel);
• this medicine may cause bleeding, particularly tumor-related bleeding. Consult your doctor if you or members of your family tend to have coagulation disorders or if you are taking blood-thinning medications for any reason;
• Aybintio may cause bleeding within or around the brain. Consult your doctor if you have metastatic brain tumors;
• Aybintio may increase the risk of bleeding in the lungs, including blood in cough or saliva. Discuss with your doctor if you have experienced these events in the past;
• Aybintio may increase the risk of developing heart failure. It is important that your doctor knows if you have previously received treatment with anthracyclines (e.g., doxorubicin, a specific type of chemotherapy used to treat certain cancers) or thoracic radiotherapy, or if you have heart disease;
• this medicine may cause infections and a reduction in neutrophil count (a type of blood cell important for protection against bacteria);
• Aybintio may cause hypersensitivity (including anaphylactic shock) and/or infusion-related reactions (reactions related to the injection of the medicine). Inform your doctor, pharmacist, or nurse if you have previously experienced problems after injections, such as dizziness/fainting, shortness of breath, swelling, or skin rashes;
• a rare neurological side effect called reversible posterior encephalopathy syndrome (PRES) has been associated with Aybintio treatment. If you experience headache, visual disturbances, confusion, or seizures with or without elevated blood pressure, contact your doctor immediately.

Talk to your doctor even if any of the above conditions occurred only in the past.
Before starting treatment with Aybintio or during treatment with Aybintio:

• if you have had or currently have mouth, tooth, and/or jaw pain, or swelling or inflammation in the mouth, or numbness or a feeling of heaviness in the jaw, or if you lose a tooth, inform your doctor and dentist immediately;
• if you need to undergo invasive dental treatment or dental surgery, inform your dentist that you are being treated with Aybintio, especially if you have received or are receiving intravenous bisphosphonate injections.

Your doctor or dentist may recommend that you undergo a dental examination before starting treatment with Aybintio.
Children and adolescents
Treatment with Aybintio is not recommended in children and adolescents under 18 years of age, as neither safety nor efficacy has been established in this patient population.
Bone tissue death (osteonecrosis) in bones other than the jaw has been observed in patients under 18 years of age treated with Aybintio.
Other medicines and Aybintio
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Combining Aybintio with another medicine called malate of sunitinib (prescribed for kidney and gastrointestinal tumors) may cause serious adverse effects. Discuss with your doctor to ensure you do not combine these medicines.
Inform your doctor if you are receiving platinum-based or taxane therapies for metastatic lung or breast cancer. These therapies in combination with Aybintio may increase the risk of serious adverse effects.
Inform your doctor if you have recently received or are currently receiving radiotherapy.
Pregnancy, breastfeeding, and fertility
You must not use this medicine if you are pregnant. Aybintio may harm the unborn child, as it can interfere with the formation of new blood vessels. Your doctor will advise you to use adequate contraceptive measures during treatment with Aybintio and for at least 6 months after the last dose of Aybintio.
If you are pregnant, suspect you may be pregnant during treatment with this medicine, or are planning a pregnancy in the near future, speak to your doctor immediately.
You must not breastfeed during treatment with Aybintio and for at least 6 months after the last dose of Aybintio, as this medicine may interfere with the child's growth and development.
Aybintio may reduce female fertility. Consult your doctor for further information.
Ask your doctor, pharmacist, or nurse for advice before taking any medicine.
Driving and using machines
Aybintio has not been shown to reduce the ability to drive vehicles or operate tools or machinery.
However, drowsiness and fainting have been reported with the use of Aybintio. If you experience symptoms affecting vision, concentration, or reaction ability, do not drive or operate machinery until symptoms resolve.
Aybintio contains sodium and polysorbate 20
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., essentially “sodium-free”.
This medicine contains 1.6 mg of polysorbate 20 per 100 mg/4 ml vial and 6.4 mg per 400 mg/16 ml vial, equivalent to 0.4 mg/ml. Polysorbates may cause allergic reactions.
Inform your doctor if you have known allergies.

3. How to use Aybintio

Dosage and frequency of administration
The required dose of Aybintio depends on body weight and the type of tumor 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 Aybintio at the appropriate dose for you. Treatment with Aybintio will be administered
once every 2 or 3 weeks. The number of infusions you receive will depend on your response to
treatment; however, you should continue receiving this treatment until Aybintio is no longer able to
block tumor growth. Your doctor will discuss this with you.

Method and route of administration
Do not shake the vial. Aybintio is a concentrate for solution for infusion. Depending on the prescribed dose,
part or all of the contents of the Aybintio vial will be diluted with a sodium chloride solution before use.
Your doctor or nurse will administer this diluted Aybintio solution as an intravenous infusion (a drip into a vein).
The first infusion will be given over 90 minutes. If this is well tolerated, the second infusion may be given over 60 minutes. Subsequent infusions may be administered over 30 minutes.

Aybintio administration must be temporarily interrupted

• if severe high blood pressure problems occur, requiring treatment with medications to control blood pressure,
• if you experience impaired wound healing after surgery,
• if you are scheduled to undergo a surgical procedure.

Aybintio administration must be permanently discontinued if any of the following occur

• severe high blood pressure that cannot be controlled with antihypertensive medicines, or sudden and severe increase in blood pressure,
• presence of protein in the urine associated with edema (body swelling),
• perforation of the intestinal wall,
• abnormal connections or passages between the trachea and esophagus, internal organs and skin, vagina and any part of the gastrointestinal tract, or between other tissues not normally connected (fistula), as judged by the doctor to be severe,
• severe skin infections or infections of deeper layers beneath the skin,
• blood clots in the arteries,
• blood clots in the pulmonary blood vessels,
• severe bleeding of any kind.

If an excessive dose of Aybintio is administered

• you may experience severe headache. In this case, contact your doctor, pharmacist, or nurse immediately.

If you miss a dose of Aybintio

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

If you stop treatment with Aybintio
Stopping treatment with Aybintio may cause the inhibition of tumor growth to cease. Do not stop treatment with Aybintio without first consulting your doctor.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any side effect, including those not listed in this leaflet, please talk to your doctor, pharmacist or nurse.
The side effects listed below have been observed in patients treated with Aybintio in combination with chemotherapy. This does not mean that these side effects were necessarily caused by Aybintio.

Allergic reactions
If you experience an allergic reaction, seek immediate medical help. Signs may include: difficulty breathing or chest pain. You may also experience skin redness or flushing, rash, chills and shivering, feeling unwell (nausea) or vomiting, swelling, dizziness, rapid heartbeat and loss of consciousness.

If you experience any of the side effects listed below, seek immediate help.

Serious side effects that may be very common (may affect more than 1 in 10 people) include:

• high blood pressure,
• 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 involved in blood clotting,
• feeling weak and lacking energy,
• tiredness,
• diarrhoea, nausea, vomiting and abdominal pain.

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

• intestinal perforation,
• bleeding, including lung bleeding in patients with non-small cell lung cancer,
• blocked arteries due to a blood clot,
• blocked veins due to a blood clot,
• blocked pulmonary blood vessels due to a blood clot,
• blocked leg veins due to 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, intestine, lungs and airways, reproductive and urinary tract,
• mouth and oesophageal ulcers which may cause pain and difficulty swallowing,
• pain, including headache, back pain and pain in the pelvic and anal area,
• localized abscesses,
• infections, particularly blood or bladder infections,
• reduced blood flow to the brain or stroke,
• drowsiness,
• nosebleeds,
• increased heart rate (palpitations),
• intestinal obstruction,
• abnormal urine test results (presence of protein in the urine),
• shortness of breath or reduced oxygen levels in the blood,
• skin infections or infections of deeper skin layers,
• fistulas: abnormal tubular connections between internal organs and the skin or other tissues not normally connected, including connections between the vagina and gastrointestinal tract in patients with cervical cancer,
• allergic reactions (signs may include difficulty breathing, facial redness, rash, low or high blood pressure, low oxygen levels in the blood, chest pain, or nausea/vomiting).

Serious side effects that are rare (may affect up to 1 in 1,000 people) include:
sudden and severe allergic reaction with difficulty breathing, swelling, dizziness, rapid heartbeat, sweating and loss of consciousness (anaphylactic shock).

Serious side effects with unknown frequency (frequency cannot be estimated from the available data) include:

• severe skin infections or infections of deeper layers under the skin, especially if you have had intestinal wall perforations or problems with wound healing,
• a negative effect on women's ability to have children (see the sections following the list of side effects for further recommendations),
• a brain condition with symptoms such as seizures, headache, confusion and vision changes (posterior reversible encephalopathy syndrome, PRES),
• symptoms suggesting changes in normal brain function (headache, visual disturbances, confusion or seizures) and high blood pressure,
• dilation and weakening of the wall of a blood vessel or a tear in the blood vessel wall (aneurysms and arterial dissections),
• blockage of small blood vessel(s) in the kidney,
• abnormally high blood pressure in the lung vessels making the right side of the heart work harder than normal,
• perforation of the cartilage wall 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, bloating, black tarry stools, blood in the stool or blood in vomit),
• bleeding from the lower part of the large intestine,
• gum lesions with exposure of jawbone that do not heal, possibly associated with pain and inflammation of surrounding tissue (see the sections following the list of side effects for further recommendations),
• gallbladder perforation (symptoms may include abdominal pain, fever and nausea/vomiting).

If you experience any of the side effects listed below, seek immediate help.

Non-serious side effects that are very common (may affect more than 1 in 10 people) include:

• constipation,
• loss of appetite,
• fever,
• eye problems (including increased tearing),
• speech disturbances,
• altered sense of taste,
• runny nose,
• dry, peeling and inflamed skin, skin colour changes,
• loss of body weight,
• nosebleeds.

Non-serious side effects that are common (may affect up to 1 in 10 people) include:

• changes in voice and hoarseness.

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

• blood clots in arteries, which may lead to stroke or heart attack,
• reduced number of white blood cells and cells involved in blood clotting,
• diarrhoea,
• feeling unwell,
• headache,
• feeling fatigued,
• high blood pressure.

Aybintio may also cause changes in laboratory test results ordered by your doctor. These include: reduced number of white blood cells, particularly neutrophils (a type of white blood cell that helps protect against infections); presence of protein in the urine; reduced levels of potassium, sodium or phosphorus (a mineral) in the blood; increased blood glucose; increased alkaline phosphatase (an enzyme) in the blood; increased serum creatinine (a protein measured in blood tests to assess kidney function); reduced haemoglobin (found in red blood cells and responsible for oxygen transport), which may be severe.

Mouth, tooth and/or jaw pain, swelling or blisters in the mouth, numbness or heaviness in the jaw, or tooth loss. These may be signs and symptoms of damage to the jawbone (osteonecrosis). Inform your doctor and dentist immediately if any of these occur.

Premenopausal women (women who have menstrual periods) may experience menstrual cycle irregularities, absence of periods, and may suffer negative effects on fertility. If you are considering having children, consult your doctor before starting treatment.

Aybintio 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, this route of administration is not authorized. When Aybintio is injected directly into the eye (unapproved use), the following side effects may occur:

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aybintio

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging and on the label of the vial after “Exp./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.
The unopened vial may be stored at temperatures not exceeding 30°C for a maximum period of 35 days. The vial must be discarded if not used within 35 days after removal from the refrigerator, even if it has been returned to the refrigerator during this period.
Diluted infusion solutions should be used immediately. If immediate use is not possible, the user is responsible for the storage duration and conditions, which normally should not exceed 24 hours at a temperature between 2°C and 8°C, unless the infusion solutions have been prepared under sterile conditions. If dilution has been carried out under sterile conditions, Aybintio is stable for 45 days at a temperature between 2°C and 8°C, plus an additional 72 hours at temperatures not exceeding 30°C.
Do not use Aybintio if you notice particulate matter or discoloration before administration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Aybintio contains

• The active substance is bevacizumab. Each mL of concentrate contains 25 mg of bevacizumab. 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 components are trehalose dihydrate, sodium phosphate, polysorbate 20 (E 432) (see section 2 “Aybintio contains sodium and polysorbate 20”), and water for injections.

Description of Aybintio and contents of the pack
Aybintio is a concentrate for solution for infusion. The concentrate is a clear liquid, 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 Aybintio pack contains one vial.

Marketing Authorisation Holder
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands
[email protected]

Manufacturer
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

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

België/Belgique/Belgien Lietuva
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Nederland/Pays-Bas/Niederlande Nyderlandai
[email protected] [email protected]

България Luxembourg/Luxemburg
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Nidderlandiya Holland/Niederlande
[email protected] [email protected]

Česká republika Magyarország
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Nizozemsko Hollandia
[email protected] [email protected]

Danmark Malta
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Holland Olanda
[email protected] [email protected]

Deutschland Nederland
Organon Healthcare GmbH Samsung Bioepis NL B.V.
Tel: 0800 3384 726 (+49 (0) 89 2040022 10) Olof Palmestraat 10, 2616 LR Delft
[email protected] Nederland
[email protected]

Eesti Norge
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Holland Nederland
[email protected] [email protected]

Ελλάδα Österreich
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Ollandía Niederlande
[email protected] [email protected]

España Polska
Organon Salud, S.L. Samsung Bioepis NL B.V.
Tel: +34 91 591 12 79 Olof Palmestraat 10, 2616 LR Delft
Holandia
[email protected]

France Portugal
Organon France Samsung Bioepis NL B.V.
Tél: +33 (0)1 57 77 32 00 Olof Palmestraat 10, 2616 LR Delft
Países Baixos
[email protected]

Hrvatska România
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Nizozemska Olanda
[email protected] [email protected]

Ireland Slovenija
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Netherlands Nizozemska
[email protected] [email protected]

Ísland Slovenská republika
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Holland Holandsko
[email protected] [email protected]

Italia Suomi/Finland
Organon Italia S.r.l. Samsung Bioepis NL B.V.
Tel: +39 06 90259059 Olof Palmestraat 10, 2616 LR Delft
Alankomaat/Nederländerna
[email protected]

Κύπρος Sverige
Samsung Bioepis NL B.V. Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft Olof Palmestraat 10, 2616 LR Delft
Ollandía Nederländerna
[email protected] [email protected]

Latvija
Samsung Bioepis NL B.V.
Olof Palmestraat 10, 2616 LR Delft
Nīderlande
[email protected]

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.
This leaflet is available in all European Union/European Economic Area languages on the European Medicines Agency website.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATIONS

In view of the available data on hyaline glomerular occlusive microangiopathy reported in the literature, including some cases with positive dechallenge, and in view of a plausible mechanism of action, the PRAC considers that a causal relationship between bevacizumab and hyaline glomerular occlusive microangiopathy is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing bevacizumab should therefore be amended accordingly.

Having reviewed the PRAC's recommendation, the Committee for Medicinal Products for Human Use (CHMP) agrees with the general conclusions and the reasoning of the recommendation.

Reasons for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions on bevacizumab, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing bevacizumab remains unchanged, subject to the proposed amendments to the product information.

The CHMP recommends a variation to the terms of the marketing authorisation(s).