Abevmy 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Abevmy 25 mg/ml concentrate for solution for infusion

bevacizumab

This medicinal product is subject to additional monitoring, which will facilitate the rapid identification of new information on its safety. You can help by reporting any side effects you may experience. Information on how to report adverse effects is included at the end of section 4.

Read the entire leaflet carefully before you start using this medicine because it contains important information for you.

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

Leaflet contents

1. What Abevmy is and what it is used for
2. What you need to know before using Abevmy
3. How to use Abevmy
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

The active substance of Abevmy is bevacizumab, a humanized monoclonal antibody (a type of protein normally produced by the immune system to help the body defend itself against infections and cancer). Bevacizumab binds selectively to a protein called vascular endothelial growth factor (VEGF), which is located on the walls of blood and lymphatic vessels in the body. The VEGF protein causes blood vessels to grow into the tumour, supplying it with nutrients and oxygen. When bevacizumab binds to VEGF, it prevents tumour growth by blocking the formation of new blood vessels that provide the nutrients and oxygen the tumour needs.

Abevmy is a medicine used to treat adult patients with advanced colorectal cancer. Abevmy will be given in combination with a chemotherapy regimen containing a fluoropyrimidine medicine.

Abevmy is also used to treat adult patients with metastatic breast cancer. When used in patients with breast cancer, it will be administered together with a chemotherapy medicine called paclitaxel or capecitabine.

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

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

Abevmy is also used to treat adult patients with advanced renal cell cancer. When used in patients with kidney cancer, it will be administered together with another type of medicine called interferon.

Abevmy is also used to treat adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. When used in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, it will be given in combination with carboplatin and paclitaxel.

When used in adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a recurrence of their disease at least 6 months after their last treatment with a platinum-based chemotherapy regimen, Abevmy will be administered in combination with carboplatin and gemcitabine or with carboplatin and paclitaxel.

When used in adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a recurrence of their disease at least 6 months after their last treatment with a platinum-based chemotherapy regimen, Abevmy will be administered in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin.

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

2. What you need to know before using Abevmy

Do not use 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 (CHO) cells 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 any condition causing inflammation in the abdomen (e.g., diverticulitis, stomach ulcer, chemotherapy-induced colitis), consult your doctor.
• Abevmy may increase the risk of developing abnormal connections (fistulas) between two organs or cavities. The risk of developing connections between the vagina and any part of the intestine may be increased if you have persistent, recurrent, or metastatic cervical cancer.
• This medicine may increase the risk of bleeding or problems with surgical wound healing. Do not use this medicine if you are scheduled for surgery, have undergone major surgery within the last 28 days, or have an unhealed surgical wound.
• Abevmy may increase the risk of developing severe skin infections or deep skin tissue infections, especially if you have experienced intestinal wall perforations or wound healing problems.
• Abevmy may increase the risk of hypertension. If you have uncontrolled high blood pressure despite medication, consult 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 bulging and weakening of a 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 or thrombi in your arteries (a type of blood vessel) may increase if you are over 65 years old, have diabetes, or have previously had blood clots or thrombi in your arteries. Consult your doctor, as blood clots or thrombi may lead to heart attack or stroke.
• Abevmy may also increase the risk of developing blood clots or thrombi in the veins (a type of blood vessel).
• This medicine may cause bleeding, especially tumor-related bleeding. Consult your doctor if you have a personal or family history of bleeding disorders (coagulation disorders) or are taking blood-thinning medications for any reason.
• Abevmy may cause bleeding in and around your brain. Consult your doctor if you have metastatic cancer affecting your brain.
• Abevmy may increase the risk of bleeding in your lungs, including coughing up blood or bloody sputum. Consult your doctor if you have previously experienced this.
• Abevmy may increase the risk of heart weakening. It is important to inform your doctor if you have ever been treated with anthracyclines (a specific type of chemotherapy used to treat certain cancers, such as doxorubicin), have received chest radiation therapy, or have a heart condition.
• This medicine may cause infections and reduce the number of neutrophils (a type of blood cell important for protection against bacteria).
• Abevmy may cause hypersensitivity reactions (including anaphylactic shock) and/or infusion-related reactions (reactions associated with the injection of the medicine).
• Consult your doctor, pharmacist, or nurse if you have previously experienced problems after injections, such as dizziness/fainting, difficulty breathing, swelling, or skin rash.
• A rare neurological side effect called reversible posterior encephalopathy syndrome (RPES) has been associated with treatment with Abevmy. If you experience headache, vision changes, confusion, or seizures (with or without high blood pressure), consult your doctor.

Please consult your doctor even if any of the situations listed above apply to you or have occurred in the past.

Before starting treatment with Abevmy or during treatment with Abevmy:

• if you have or have had mouth, teeth, and/or jaw pain, swelling or sores in the mouth, numbness or heaviness in the jaw, or tooth loss, 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 are also receiving or have received intravenous bisphosphonate injections.

Before starting treatment with Abevmy, you may be advised to have a dental examination.

Children and adolescents

Use of Abevmy is not recommended in children and adolescents under 18 years of age, as safety and benefit have not been established in these patients.

Cases of bone tissue death (osteonecrosis) in bones other than the jaw have been reported in patients under 18 years of age treated with Abevmy.

Other medicines and Abevmy

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines.

Combining Abevmy with another medicine called sunitinib maleate (used for kidney and gastrointestinal cancer) may cause severe adverse effects. Consult your doctor to ensure you do not combine these medicines.

Consult your doctor if you are receiving platinum-based or taxane-based therapy for metastatic breast or lung cancer. These treatments, when combined with Abevmy, may increase the risk of serious adverse effects.

Inform your doctor if you have recently received or are currently receiving radiation therapy.

Pregnancy, breastfeeding, and fertility

Do not use Abevmy if you are pregnant. Abevmy may harm the fetus, as it can inhibit the formation of new blood vessels. Your doctor must advise you to use an effective method of contraception during treatment with Abevmy and for at least 6 months after the last dose of Abevmy.

Inform your doctor immediately if you are already pregnant, become pregnant during treatment with Abevmy, or plan to become pregnant in the near future.

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 your baby's growth and development.

Abevmy may affect female fertility. Consult your doctor for further information.

Consult your doctor, pharmacist, or nurse before using any medicine.

Driving and using machines

Abevmy has not been shown to impair your ability to drive or operate tools or machines. However, drowsiness and fainting have been reported with the use of Abevmy. If you experience symptoms affecting your vision or concentration, or your reaction ability, do not drive or use machines until symptoms resolve.

Abevmy contains sodium.

This medicine contains 4.196 mg of sodium (the main component of table/cooking salt) in each 4 ml vial. This corresponds to 0.21% of the maximum daily sodium intake recommended for an adult.

This medicine contains 16.784 mg of sodium (the main component of table/cooking salt) in each 16 ml vial. This corresponds to 0.84% of the maximum daily sodium intake recommended for an adult.

3. How to use Abevmy

Dosage and frequency of administration

The required dose of Abevmy depends on your body weight and the type of cancer being treated. The recommended dose is 5 mg, 7.5 mg, 10 mg, or 15 mg per kg of body weight. Your doctor will prescribe the appropriate dose of Abevmy for you. You will receive treatment with Abevmy once every 2 or 3 weeks. The number of infusions you receive will depend on how you respond to treatment, and you should continue treatment until Abevmy is no longer able to inhibit tumor growth. Your doctor will discuss these aspects 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, either a portion or the entire contents of the Abevmy vial will be diluted with sodium chloride solution prior to administration. A doctor or nurse will administer this diluted Abevmy solution to you as an intravenous infusion (a drip into your veins). The first infusion will be given over 90 minutes. If you tolerate this infusion well, the second infusion may be administered over 60 minutes. Subsequent infusions may be given over 30 minutes.

Administration of Abevmy must be temporarily interrupted if you:

• develop severe hypertension requiring treatment with antihypertensive medications,
• experience wound healing complications after surgery,
• have recently undergone surgery.

Administration of Abevmy must be permanently discontinued if you have:

• severe hypertension that cannot be controlled with antihypertensive medications, or if there is a sudden and severe increase in blood pressure,
• protein in the urine accompanied by body swelling,
• a perforation in the intestinal wall,
• a severe abnormal tubular or fistulous connection (fistula) between the trachea and esophagus (the tube leading to the stomach), between internal organs and the skin, between the vagina and any part of the intestine, or between other tissues that are normally not connected, as determined by your doctor,
• severe skin infections or deep skin infections,
• arterial embolism (blood clot in the arteries),
• pulmonary embolism (blood clot in the lung blood vessels),
• any severe bleeding.

If you use more Abevmy than you should

• you may experience severe headache. If this occurs, you must inform your doctor, pharmacist, or nurse immediately.

If you forget to use Abevmy

• your doctor will decide when your next dose of Abevmy should be administered. You must inform your doctor about this missed dose.

If you interrupt treatment with Abevmy

Interrupting treatment with Abevmy may reduce its effect on tumor growth.

Do not interrupt treatment with Abevmy unless you have discussed it with your doctor.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if these adverse effects are not listed in this leaflet.

The adverse effects listed below have been observed when Abevmy is administered with chemotherapy. This does not necessarily mean that these adverse effects were strictly caused by Abevmy.

Allergic reactions

If you have an allergic reaction, consult your doctor or healthcare professional immediately. Signs may include: difficulty breathing or chest pain. You may also experience redness or flushing of the skin, rash, chills and shivering, dizziness (nausea), or feeling unwell (vomiting), swelling, dizziness, rapid heartbeat, and loss of consciousness.

Seek immediate medical help if you experience any of the following adverse effects.

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

• high blood pressure,
• numbness or tingling sensation in hands or feet,
• decrease in blood cell counts, including white blood cells that help fight infections (this may be accompanied by fever), and platelets that help blood to clot,
• feeling weak and lacking energy,
• fatigue,
• diarrhea, nausea, vomiting, and abdominal pain.

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

• intestinal perforation,
• bleeding, including pulmonary hemorrhage in patients with non-small cell lung cancer,
• arterial blockage due to embolism,
• venous blockage due to embolism,
• pulmonary vessel blockage due to embolism,
• leg vein blockage due to embolism,
• heart failure,
• problems with wound healing after surgery,
• redness, peeling, sensitivity, pain, or blisters on fingers or feet,
• decrease in red blood cell count,
• lack of energy,
• stomach and intestinal disturbances,
• muscle and joint pain, muscle weakness,
• dry mouth combined with thirst and/or reduced or dark-colored urine,
• inflammation of the mucosal lining of the mouth and intestine, lungs and airways, reproductive organs, and urinary tract,
• mouth sores and sores in the tube connecting the mouth to the stomach, which may be painful and cause difficulty swallowing,
• pain, including headache, back pain, pelvic pain, and anal region pain,
• localized areas of pus,
• infection, particularly blood or bladder infection,
• reduced blood flow to the brain or stroke,
• drowsiness,
• nosebleeds,
• increased heart rate (pulse),
• intestinal obstruction,
• abnormal urine test (proteins in urine),
• difficulty breathing or decreased blood oxygen levels,
• skin infections or infections of deeper skin layers,
• fistula: abnormal tubular connection between internal organs and the skin or other tissues that are not normally connected, including connections between the vagina and intestine in patients with cervical cancer,
• allergic reactions (signs may include difficulty breathing, facial redness, skin rash, low or high blood pressure, low oxygen levels in blood, chest pain, or nausea/vomiting).

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

• severe skin infections or infections of deeper skin layers, especially if you had intestinal wall perforations or wound healing problems,
• negative effect on a woman's ability to have children (see below for further recommendations),
• brain disease with symptoms such as seizures (fits), headache, confusion, and vision disturbances (Posterior Reversible Encephalopathy Syndrome or PRES),
• symptoms suggesting changes in normal brain function (headaches, vision disturbances, confusion, or seizures), and high blood pressure,
• enlargement and weakening of the wall of a blood vessel or tear in the blood vessel wall (aneurysms and arterial dissections),
• blockage of small blood vessels in the kidney,
• abnormally high pressure in the blood vessels of the lungs, causing the right side of the heart to work harder than normal,
• perforation in the cartilage wall separating the nasal openings,
• perforation of the stomach or intestine,
• ulcer or perforation in the lining of the stomach or small intestine (these signs may include abdominal pain, bloating sensation, black stools, blood in stool, or blood in vomit),
• bleeding from the lower part of the large intestine,
• gum lesions with exposed jawbone that do not heal and may be associated with pain and inflammation of surrounding tissues (for further recommendations, see the list of adverse effects in the paragraph below),
• gallbladder perforation (symptoms and signs may include abdominal pain, fever, nausea, and vomiting).

If you notice any of these adverse effects listed above, seek medical attention as soon as possible.

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

• constipation,
• loss of appetite,
• fever,
• eye problems (including increased tear production),
• speech disturbances,
• taste disturbances,
• nasal discharge,
• dry skin, skin peeling and inflammation, changes in skin color,
• weight loss,
• nosebleeds.

Non-serious adverse 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 an increased risk of experiencing the following:

• arterial embolism that may lead to stroke or heart attack,
• reduction in white blood cells and platelets (which help with clotting) in blood,
• diarrhea,
• malaise,
• headache,
• fatigue,
• high blood pressure.

Abevmy may also cause changes in laboratory tests performed by your doctor. These changes may include a reduction in white blood cell counts, particularly neutrophils (a type of white blood cell that helps protect against infections), presence of proteins in urine, decreased levels of potassium, sodium, or phosphorus in blood, increased blood sugar, increased alkaline phosphatase (an enzyme) in blood, decreased hemoglobin (found in red blood cells and responsible for oxygen transport), which may be severe.

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

Premenopausal women (women who have menstrual cycles) may notice that their periods become irregular or stop and may experience fertility problems. If you are considering having children, 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 injection into the eye. Therefore, it is not authorized for this use. When Abevmy is injected directly into the eye (unauthorized use), the following side effects may occur:

• Eye infection or inflammation of the eyeball,
• Eye redness, small particles or spots in vision (floaters), eye pain,
• Seeing flashes of light with floaters, progressing to partial vision loss,
• Increased eye pressure,
• Bleeding in the eye.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if these effects are not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Abevmy

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the pack and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

The solution for infusion should be administered immediately after dilution. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should normally not exceed 24 hours between 2 °C and 8 °C, unless the infusion solutions have been prepared under sterile conditions. When dilution has been performed under sterile conditions, Abevmy is stable for up to 70 days between 2 °C and 8 °C and for up to 15 days between 23 °C and 27 °C.

Do not use Abevmy if you notice any foreign particles or discoloration before administration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Abevmy

• The active substance is bevacizumab. Each ml of concentrate contains 25 mg of bevacizumab, corresponding to 1.4 or 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”.

Appearance of the product and contents of the container

Abevmy is a concentrate for solution for infusion. The concentrate is a liquid, colourless to pale brown, clear to slightly opalescent, without visible particles. It is supplied 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.

Only certain 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

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: 09/2024

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.