ABEVMY 25 mg/mL concentrate for infusion solution

2. What you need to know before you use Abevmy

Do not use Abevmy if:

• you are allergic (hypersensitive) to bevacizumab or 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 you are given Abevmy:

• Abevmy may increase the risk of perforation of the intestine wall. If you have any disease that causes inflammation in the abdomen (e.g., diverticulitis, stomach ulcer, chemotherapy-induced colitis), talk to your doctor.
• Abevmy may increase the risk of developing an abnormal connection between two organs or vessels. The risk of developing a connection between the vagina and any part of the intestine may increase if you have persistent, recurrent, or metastatic cervical cancer.
• This medicine may increase the risk of bleeding or problems with wound healing after surgery. If you are going to have surgery, have had major surgery in the last 28 days, or have an open wound, you should not use this medicine.
• Abevmy may increase the risk of developing severe skin or deep skin infections, especially if you have had perforation of the intestine wall or problems with wound healing.
• Abevmy may increase the risk of high blood pressure. If you have uncontrolled high blood pressure, talk to your doctor, it is important to make sure your blood pressure is under control before starting treatment with Abevmy.
• This medicine may increase the risk of having protein in your urine, especially if you already have high blood pressure.
• The risk of developing blood clots or blockages in your arteries (a type of blood vessel) may increase if you are over 65 years old, if you have diabetes, or if you have had blood clots or blockages in your arteries in the past. Talk to your doctor, as blood clots or blockages can cause a heart attack and stroke.
• Abevmy may also increase the risk of developing blood clots or blockages in your veins (a type of blood vessel).
• This medicine may cause bleeding, especially bleeding related to the tumor. Talk to your doctor if you have a history of or are at risk of bleeding disorders (bleeding) or are taking medicines that thin your blood for any reason.
• Abevmy may cause bleeding in and around your brain. Talk to your doctor if you have metastatic cancer that affects your brain.
• Abevmy may increase the risk of bleeding in your lungs, including coughing up blood. Talk to your doctor if you have noticed this before.
• Abevmy may increase the risk of your heart becoming weaker. It is important that you tell your doctor if you have ever been treated with anthracyclines (a specific type of chemotherapy used to treat some types of cancer, such as doxorubicin) or have received radiation therapy to the chest, or if you have heart disease.
• This medicine may cause infections and decrease the number of neutrophils (a type of blood cell important for your protection against bacteria).
• Abevmy may cause hypersensitivity (including anaphylactic shock) and/or infusion-related reactions (reactions related to the injection of the medicine).
• Talk to 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 posterior reversible encephalopathy syndrome (PRES) has been associated with treatment with Abevmy. If you have a headache, changes in vision, confusion, or seizures with or without high blood pressure, talk to your doctor.

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

Before starting treatment with Abevmy or during treatment with Abevmy:

Before you start treatment with Abevmy, you may be advised to have a dental check-up.

Children and adolescents

Abevmy is not recommended for use in children and adolescents under 18 years of age, as the safety and benefits in these patients have not been established.

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

Other medicines and Abevmy

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines.

The combination of Abevmy with another medicine called sunitinib malate (prescribed for kidney or gastrointestinal cancer) may cause serious side effects. Talk to your doctor to make sure you do not combine these medicines.

Talk to your doctor if you are receiving platinum-based or taxane-based therapy for metastatic breast or lung cancer. These therapies in combination with Abevmy may increase the risk of serious side effects.

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

Pregnancy, breastfeeding, and fertility

Do not use Abevmy if you are pregnant. Abevmy may harm your unborn baby, as it may prevent the formation of new blood vessels. Your doctor must advise you to use a contraceptive method 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.

Do not breastfeed your baby during treatment with Abevmy and for at least 6 months after the last dose of Abevmy, as this medicine may interfere with the growth and development of your baby.

Abevmy may affect female fertility. Talk to your doctor for more information.

Talk to your doctor, pharmacist, or nurse before using any medicine.

Driving and using machines

Abevmy has not been shown to reduce your ability to drive or use tools or machines. However, somnolence and fainting have been reported with the use of Abevmy. If you experience symptoms that affect your vision or concentration, or your ability to react, do not drive or use machines until the symptoms disappear.

Abevmy contains sodium.

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

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

3. How to use Abevmy

Dose and frequency of administration

The dose of Abevmy you need depends on your weight and the type of cancer being treated. The recommended dose is 5 mg, 7.5 mg, 10 mg, or 15 mg per kilogram of body weight. Your doctor will prescribe a dose of Abevmy that is right 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 should continue until Abevmy is no longer able to slow down tumor growth. Your doctor will discuss these aspects with you.

Form and route of administration

Do not shake the vial.

Abevmy is a concentrate for solution for infusion. Depending on the dose prescribed for you, a fraction or all of the contents of the Abevmy vial will be diluted with sodium chloride solution before administration. A doctor or nurse will give you this diluted Abevmy solution as an intravenous infusion (by drip into your veins). The first infusion will be given over 90 minutes. If you tolerate this infusion well, the second infusion can be given over 60 minutes. Subsequent infusions can be given over 30 minutes.

Abevmy administration must be temporarily interrupted:

Abevmy administration must be permanently stopped if you have:

• severe high blood pressure that cannot be controlled with blood pressure medicines; or if you have a sudden and severe increase in blood pressure,
• protein in your urine accompanied by swelling of your body,
• a perforation in the intestine wall,
• a fistula (an abnormal connection between two organs or vessels) that your doctor considers serious,
• severe skin or deep skin infections,
• blood clots in your arteries,
• blood clots in the blood vessels in your lungs,
• any severe bleeding.

If you use more Abevmy than you should

• you may have severe migraine. If this happens, you should tell your doctor, pharmacist, or nurse immediately.

If you forget to use Abevmy

• your doctor will decide when you should receive your next dose of Abevmy. You should tell your doctor about the missed dose.

If you stop using Abevmy

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

Do not stop treatment with Abevmy unless you have talked to your doctor.

If you have any further questions on 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 all people suffer from them.

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is an adverse effect that does not appear in this leaflet.

The adverse effects mentioned 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. The signs may include: difficulty breathing or chest pain. You may also experience redness or flushing of the skin or rash, chills and tremors, feeling of dizziness (nausea) or feeling of discomfort (vomiting), swelling, dizziness, rapid heartbeat, and loss of consciousness.

You should seek help immediately if you suffer from any of the adverse effects mentioned below.

The serious adverse effects that may be very frequent(may affect more than 1 in 10 people) include:

• high blood pressure,
• feeling of numbness or tingling in hands or feet,
• decrease in the number of blood cells, including white blood cells that help fight infections (this may be accompanied by fever), and platelets that help blood clot,
• feeling of weakness and lack of energy,
• fatigue,
• diarrhea, nausea, vomiting, and abdominal pain.

The serious adverse effects that may be frequent(may affect up to 1 in 10 people) include:

• perforation of the intestine,
• bleeding, including hemorrhage in the lungs in patients with non-small cell lung cancer,
• blockage of the arteries by embolism,
• blockage of the veins by embolism,
• blockage of the blood vessels in the lungs by embolism,
• blockage of the veins in the legs by embolism,
• heart failure,
• problems with wound healing after surgery,
• redness, peeling, sensitivity, pain, or blisters on the fingers or toes,
• decrease in the number of red blood cells,
• lack of energy,
• stomach and intestine problems,
• muscle and joint pain, muscle weakness,
• dry mouth combined with thirst and/or reduced or dark urine output,
• inflammation of the mucous membrane lining of the mouth and intestine, lungs and airways, reproductive system and urinary tract,
• sores in the mouth and the tube that goes from the mouth to the stomach, which can be painful and cause difficulty swallowing,
• pain, including headache, back pain, pelvic and anal regions,
• localized pus pockets,
• infection, and in particular infection in the blood or bladder,
• decrease in blood flow to the brain or stroke,
• drowsiness,
• nosebleeds,
• increased heart rate (pulse),
• intestinal obstruction,
• abnormal urine test (protein in the urine),
• difficulty breathing or decreased oxygen levels in the blood,
• skin or deep tissue infections,
• fistula: abnormal tube-like communication between internal organs and the skin or other tissues that are not normally connected, including communications between the vagina and intestine in patients with cervical cancer,
• allergic reactions (the signs may include difficulty breathing, facial redness, skin rash, low or high blood pressure, low oxygen levels in the blood, chest pain, or nausea/vomiting).

The serious adverse effects that may be rare(may affect up to 1 in 1000 people) include:

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

The serious adverse effects of unknown frequency(cannot be estimated from the available data) include:

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

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

The adverse effects that are very frequent(may affect more than 1 in 10 people) and are not serious are:

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

The adverse effects that are frequent(may affect up to 1 in 10 people) and are not serious are:

• changes in voice and hoarseness.

Patient over 65 years of age have a higher risk of experiencing the following:

• embolism in the arteries that can cause stroke or heart attack,
• reduction in the number of white blood cells and platelets (that help with blood clotting) in the blood,
• diarrhea,
• discomfort,
• headache,
• fatigue,
• high blood pressure.

Abevmy may also cause changes in laboratory tests that your doctor performs. These changes may include a reduction in the number of white blood cells in the blood, in particular neutrophils (a type of white blood cell that helps fight infections), presence of protein in the urine, decrease in potassium, sodium, or phosphorus in the blood, increase in blood sugar, increase in alkaline phosphatase (an enzyme) in the blood, decrease in hemoglobin (which is found in red blood cells and carries oxygen), which can be severe.

Pain in the mouth, teeth, and/or jaw, swelling or sores in the mouth, numbness or feeling of heaviness in the jaw, or loss of a tooth. These may be signs and symptoms of jawbone damage (osteonecrosis). Report immediately to your doctor and dentist if you experience any of them.

Pre-menopausal women (women who have a menstrual cycle) may notice that their periods become irregular or disappear and may experience fertility problems. If you are thinking of having children, you should consult your doctor before starting treatment.

Abevmy has been developed and manufactured to treat cancer by injection into the bloodstream. It has not been developed or manufactured for injection into the eye. Therefore, it is not authorized for use in this way. When Abevmy is injected directly into the eye (unapproved use), the following side effects may occur:

• Infection or inflammation of the eyeball,
• Redness of the eye, small particles or spots in the vision (floaters), eye pain,
• Flashes of light with floaters, with progression to partial loss of vision,
• Increased eye pressure,
• Bleeding in the eye.

Reporting of Adverse Effects

If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if it is an adverse effect that does not appear in this leaflet. You can also report them directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing 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 expiration date that appears on the packaging and on the label of the vial after CAD. The expiration date is the last day of the month indicated.

Store in the 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 it is not used immediately, the storage times and conditions are the responsibility of the user and should not normally exceed 24 hours between 2 °C and 8 °C, unless the infusion solutions have been prepared in a sterile environment. When the dilution is performed in a sterile environment, Abevmy is stable for a period of up to 70 days between 2 °C and 8 °C and a period of up to 15 days between 23 °C and 27 °C.

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

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

6. Package Contents and Additional Information

Composition of Abevmy

• The active ingredient 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 ingredients are sodium phosphate (E339), α, α-trehalose dihydrate, polysorbate 20 (E432), and water for injectable preparations. See section 2 "Abevmy contains sodium".

Appearance of the Product and Package Contents

Abevmy is a concentrate for solution for infusion. The concentrate is a colorless to pale brown liquid and transparent to slightly opalescent without visible particles. It comes 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 some pack sizes may be marketed.

Marketing Authorization 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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet: 09/2024

Other Sources of Information

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