Abevmy

Package leaflet: Information for the user

Abevmy 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 possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Abevmy is and what it is used for

Abevmy 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" (VEGF),
which is present on the lining of the blood and lymphatic vessels in the body. The VEGF protein
promotes the growth of blood vessels within the tumour; these blood vessels supply the tumour with
nutrients and oxygen. Once bevacizumab binds to VEGF, tumour growth is inhibited by blocking the
development of blood vessels that supply nutrients and oxygen to the tumour.

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

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

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

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

Abevmy is furthermore used to treat adult patients with advanced renal cell carcinoma. In patients with
this type of cancer, bevacizumab will be administered together with another type of medicine called
interferon.

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

Abevmy 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 carcinoma,
or primary peritoneal carcinoma whose disease has recurred at least 6 months after the last time they
were treated with a platinum-containing chemotherapy regimen.

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

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

2. What you should know before receiving Abevmy

Do not receive Abevmy if:

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before receiving Abevmy:

• Abevmy 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;
• Abevmy may increase the risk of developing abnormal connections or passages between two organs or blood vessels. Persistent, recurrent, or metastatic cervical carcinoma may increase the risk of developing connections between the vagina and any section of the gastrointestinal tract;
• this medicine may increase the risk of bleeding or impair wound healing after surgery. If you are scheduled for surgery, if you have undergone major surgery within the past 28 days, or if you have an unhealed surgical wound, you should not receive this medicine;
• Abevmy 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 impaired wound healing;
• Abevmy may increase the incidence of high blood pressure. If you have uncontrolled high blood pressure despite medication, discuss this with your doctor. It is important to ensure your blood pressure is well-controlled before starting treatment with Abevmy;
• if you have or have had an aneurysm (a weakened and dilated blood vessel wall) or a tear in the wall of a blood vessel;
• this medicine increases the risk of 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 old, if you have diabetes, or if you have had previous arterial blood clots.

• Talk to your doctor, as blood clots can lead to heart attacks and strokes.
• Abevmy 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 bleeding or clotting disorders, or if you are taking blood-thinning medications for any reason;
• Abevmy may cause bleeding within or around the brain;
• consult your doctor if you have brain metastases;
• Abevmy may increase the risk of bleeding in the lungs, including coughing up blood or blood in saliva. Discuss with your doctor if you have experienced these events in the past;
• Abevmy may increase the risk of developing heart failure. It is important that your doctor knows if you have previously received anthracycline therapy (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);
• Abevmy 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 treatment with Abevmy. If you experience headache, visual disturbances, confusion, or seizures with or without elevated blood pressure, contact your doctor immediately.

Also contact your doctor if any of the above conditions occurred in the past. Before starting
treatment with Abevmy or during treatment with Abevmy:

• if you have had or currently have mouth, teeth, and/or jaw pain, swelling or inflammation in the mouth, 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 Abevmy, especially if you have received or are receiving intravenous bisphosphonate injections.

Your doctor or dentist may recommend a dental examination before starting
treatment with Abevmy.
Children and adolescents
Treatment with Abevmy 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 Abevmy.
Other medicines and Abevmy
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Combining Abevmy with another medicine called sunitinib malate (used 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 Abevmy 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
Do not use this medicine if you are pregnant. Abevmy may harm the unborn child, as it can interfere with the formation of new blood vessels. Your doctor will advise you to use effective contraception during treatment with Abevmy and for at least 6 months after the last dose of Abevmy.
If you are pregnant, suspect you are 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 Abevmy and for at least 6 months after the last dose of Abevmy, as this medicine may interfere with the infant's growth and development.
Abevmy 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
Abevmy has not been shown to impair the ability to drive or operate machinery.
However, drowsiness and fainting have been reported with the use of Abevmy. If you experience symptoms affecting vision, concentration, or reaction ability, do not drive or operate machinery until symptoms resolve.
Abevmy contains sodium
This medicine contains 4.196 mg of sodium (the main component of table salt) in each 4 mL vial. This corresponds to 0.21% of the maximum daily dietary intake recommended for an adult.
This medicine contains 16.784 mg of sodium (the main component of table salt) in each 16 mL vial. This corresponds to 0.84% of the maximum daily dietary intake recommended for an adult.

3. How Abevmy is administered

Dosage and frequency of administration
The required dose of Abevmy depends on body weight and the type of tumour 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 Abevmy at the appropriate dose for you. Treatment with Abevmy 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 Abevmy is no longer able to block tumour growth. Your doctor will discuss this with you.

Method and route of administration
Do not shake the vial.
Abevmy is a concentrate for solution for infusion. Depending on the prescribed dose, part of the vial contents or the entire vial of Abevmy will be diluted with sodium chloride solution before use. Your doctor or nurse will administer this diluted Abevmy 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.

Administration of Abevmy must be temporarily interrupted

• if severe high blood pressure problems occur that require treatment with medicines to control blood pressure,
• if you have wound healing problems after surgery,
• if you are scheduled for a surgical procedure.

Administration of Abevmy must be permanently discontinued if any of the following problems 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 body swelling (oedema),
• perforation of the intestinal wall,
• an abnormal connection or passage between the trachea and oesophagus, internal organs and skin, vagina and any part of the gastrointestinal tract, or between other tissues not normally connected (fistula), considered severe by the doctor,
• 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 overdose of Abevmy is administered

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

If you miss a dose of Abevmy

• Your doctor will decide the most appropriate time for you to receive the next dose of Abevmy. Please discuss this with your doctor.

If you stop treatment with Abevmy
Stopping treatment with Abevmy may cause the inhibition of tumour growth to cease. Do not stop treatment with Abevmy without first discussing it with your doctor.
If you have any questions 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 experience any side effect, including those not listed in this leaflet, speak to your doctor, pharmacist or nurse.
The side effects listed below have been observed in patients treated with Abevmy in combination with chemotherapy. This does not mean that these side effects were necessarily caused by Abevmy.

Allergic reactions
If you have an allergic reaction, tell your doctor or a healthcare professional immediately. 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 described below, seek immediate help.

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

• high blood pressure,
• tingling or numbness in the hands or feet,
• reduction in 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 blood clots,
• blocked veins due to blood clots,
• blocked pulmonary blood vessels due to blood clots,
• blocked leg veins due to blood clots,
• heart failure,
• poor wound healing after surgery,
• redness, peeling, soreness, pain or blistering on the fingers or toes,
• reduction in red blood cells,
• lack of energy,
• stomach and intestinal problems,
• muscle and joint pain, muscle weakness,
• dry mouth associated with thirst and/or reduced or dark urine,
• inflammation of the mucous membranes in the mouth, intestine, lungs and airways, reproductive and urinary tracts,
• mouth and oesophageal ulcers that 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 (pulsations),
• intestinal blockage,
• changes in urine tests (presence of protein in urine),
• shortness of breath or low oxygen levels in the blood,
• skin infections or infections of deeper skin layers,
• fistulas: abnormal tubular connections between internal organs and 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 may be 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 available data) include:

• severe skin infections or infections in deeper layers under the skin, especially if you have had intestinal wall perforations or wound healing problems,
• a negative effect on women’s fertility (see the paragraphs following the side effect list for further recommendations),
• a brain condition with symptoms such as seizures, headache, confusion and vision changes (reversible posterior 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,
• stomach or intestinal perforation,
• 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 stools or blood in vomit),
• bleeding from the lower part of the large intestine,
• gum lesions with exposed jawbone that do not heal, possibly associated with pain and inflammation of surrounding tissue (see the paragraphs following the side effect list for further recommendations),
• gallbladder perforation (symptoms may include abdominal pain, fever and nausea/vomiting).

If you experience any of the side effects described below, seek help as soon as possible.

Side effects that are very common (may affect more than 1 in 10 people), which are not serious, include:

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

Side effects that are common (may affect up to 1 in 10 people), which are not serious, include:

• voice changes 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,
• reduction in white blood cells and cells involved in blood clotting,
• diarrhoea,
• feeling unwell,
• headache,
• tiredness,
• high blood pressure.

Abevmy may also cause changes in laboratory test results prescribed 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 urine, reduced potassium, sodium or phosphorus (a mineral) in blood, increased blood sugar, increased alkaline phosphatase (an enzyme) in blood, increased serum creatinine (a protein measured in blood tests to assess kidney function), reduced haemoglobin (found in red blood cells and carries oxygen), which may be severe.

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

Premenopausal women (women who have menstrual periods) may experience menstrual irregularities, absence of menstruation, and may have negative effects on fertility. If you are considering having children, you should discuss this with your doctor before starting treatment.

Abevmy has been developed and manufactured for cancer treatment via intravenous injection. It has not been developed or manufactured for administration by injection into the eye. Therefore, this route of administration is not authorised.

When Abevmy is injected directly into the eye (unapproved use), the following side effects may occur:

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, speak 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 Abevmy

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 vial label after the abbreviation “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 should be used immediately after dilution.
If not used immediately, the storage times and conditions during use are the responsibility of the user and should normally not exceed 24 hours at a temperature of 2°C to 8°C, unless the infusion solutions have been prepared under sterile conditions. When dilution has been carried out under sterile conditions, Abevmy is stable for up to 70 days at a temperature of 2°C to 8°C and for up to 15 days at a temperature of 23°C to 27°C.
Do not use Abevmy if you notice particles or changes in colour before administration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Abevmy 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 components are sodium phosphate (E339), α,α-trehalose dihydrate, polysorbate 20 (E432), and water for injections. See section 2 “Abevmy contains sodium”.

Description of the appearance of Abevmy and contents of the pack
Abevmy is a concentrate for solution for infusion. The concentrate is a liquid that ranges from clear to slightly opalescent and from colourless to light brown, free from visible particles. It is contained in a glass vial with a rubber stopper. The 4 mL vials are available in packs containing 1 or 5 vials. The 16 mL vials are available in packs containing 1, 2 or 3 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36 Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
Ireland D13 R20R

Manufacturers
Biosimilar Collaborations Ireland Limited
Block B,
The Crescent Building,
Santry Demesne
Dublin
D09 C6X8
Ireland

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

België/Belgique/Belgien Lietuva
Biocon Biologics Belgium BV Biosimilar Collaborations Ireland Limited
Tél/Tel: 0080008250910 Tel: 0080008250910

България Luxembourg/Luxemburg
Biosimilar Collaborations Ireland Limited Biocon Biologics France S.A.S
Тел: 0080008250910 Tél/Tel: 0080008250910

Česká republika Magyarország
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel.: 0080008250910

Danmark Malta
Biocon Biologics Finland OY Biosimilar Collaborations Ireland Limited
Tlf: 0080008250910 Tel.: 0080008250910

Deutschland Nederland
Biocon Biologics Germany GmbH Biocon Biologics France S.A.S
Tel: 0080008250910 Tel: 0080008250910

Eesti Norge
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Tel: 0080008250910 Tlf: +47 800 62 671

Ελλάδα Österreich
Biocon Biologics Greece ΜΟΝΟΠΡΟΣΩΠΗ Biocon Biologics Germany GmbH
Ι.Κ.Ε Tel: 0080008250910
Τηλ.: 0080008250910

España Polska
Biocon Biologics Spain S.L. Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910

France Portugal
Biocon Biologics France S.A.S Biocon Biologics Spain S.L.
Tel: 0080008250910 Tel: 0080008250910

Hrvatska România
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910

Ireland Slovenija
Biosimilar Collaborations Ireland Limited Biosimilar Collaborations Ireland Limited
Tel: 1800 777 794 Tel: 0080008250910

Ísland Slovenská republika
Biocon Biologics Finland OY Biocon Biologics Germany GmbH
Sími: +345 800 4316 Tel: 0080008250910

Italia Suomi/Finland
Biocon Biologics Spain S.L. Biocon Biologics Finland OY
Tel: 0080008250910 Puh/Tel: 99980008250910

Κύπρος Sverige
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Τηλ: 0080008250910 Tel: 0080008250910

Latvija
Biosimilar Collaborations Ireland Limited
Tel: 0080008250910

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