Aybintio 25 mg/ml concentrado para solucion para perfusion

Prospect: Information for the Patient

Aybintio 25 mg/ml Concentrate for Solution for Infusion

bevacizumab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

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

The active ingredient of Aybintio is bevacizumab, a humanized monoclonal antibody (a type of protein that is normally produced by the immune system to help the body defend itself against infections and cancer). Bevacizumab selectively binds to a protein called vascular endothelial growth factor (VEGF, English acronym), which is located in the walls of blood and lymphatic vessels of the body. The VEGF protein causes blood vessels to grow within the tumor, which supplies it with nutrients and oxygen. When bevacizumab binds to VEGF, it prevents tumor growth by blocking the growth of blood vessels, which provide the necessary nutrients and oxygen for the tumor.

Aybintio is a medication used for the treatment of adult patients with advanced colorectal or rectal cancer. Aybintio will be administered in combination with a chemotherapy regimen containing a fluoropyrimidine medication.

Aybintio is also used for the treatment of adult patients with metastatic breast cancer. When used in patients with breast cancer, it will be administered with a chemotherapy medication called paclitaxel or capecitabine.

Aybintio is also used for the treatment of adult patients with advanced non-small cell lung cancer. Aybintio will be administered along with a platinum-based chemotherapy regimen.

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

Aybintio is also used for the treatment of adult patients with advanced renal cancer. When used in patients with renal cancer, it will be administered with another type of medication called interferon.

Aybintio is also used for the treatment of 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 administered in combination with carboplatin and paclitaxel.

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

Aybintio is also used for the treatment of adult patients with persistent, recurrent, or metastatic cervical cancer. Aybintio will be administered in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum-based therapy..

No use Aybintio

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

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Aybintio:

• Aybintio may increase the risk of causing perforations in the intestinal wall. If you have any disease that causes inflammation in the abdomen (e.g. diverticulitis, stomach ulcer, chemotherapy-induced colitis), consult your doctor.

• Aybintio may increase the risk of developing an abnormal communication between two organs or vesicles. The risk of developing communications between the vagina and any part of the intestine may increase if you have persistent, recurrent, or metastatic cervical cancer.

• This medication may increase the risk of bleeding or problems with wound healing. If you are to be operated on, have had major surgery in the last 28 days, or have an unhealed surgical wound, do not use this medication.

• Aybintio may increase the risk of developing severe skin infections or deep tissue infections, especially if you have had intestinal perforations or wound healing problems.

• Aybintio may increase the risk of hypertension. If you have uncontrolled high blood pressure, consult your doctor, it is essential to ensure that your blood pressure is controlled before starting treatment with Aybintio.

• If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.

• This medication increases the risk of having protein in the urine, especially if you already have high blood pressure.

• The risk of developing thrombi or clots 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 thrombi or clots in your arteries in the past. Consult your doctor, as thrombi or clots can cause heart attacks and strokes.

• Aybintio may also increase the risk of developing thrombi or clots in your veins (a type of blood vessel).

• This medication may cause bleeding, especially tumor-related bleeding. Consult your doctor if you have a tendency or family history of bleeding disorders or are taking medications that thin the blood for any reason.

• Aybintio may cause bleeding in and around your brain. Consult your doctor if you have metastatic cancer that affects your brain.

• Aybintio may increase the risk of bleeding in your lungs, including coughing or expectoration of blood. Consult your doctor if you have noticed this previously.

• Aybintio may increase the risk of heart failure. It is essential to inform your doctor if you have ever been treated with anthracyclines (a specific type of chemotherapy used to treat certain types of cancer, such as doxorubicin) or have received radiation therapy in the chest, or if you have a heart disease.

• This medication may cause infections and decrease the number of neutrophils (a type of blood cell important for protecting against bacteria).

• Aybintio may cause hypersensitivity (including anaphylactic reactions) and/or reactions after infusion (reactions related to the injection of the medication). Consult your doctor, pharmacist, or nurse if you have previously experienced problems after injections, such as dizziness/dizziness, difficulty breathing, swelling, or skin rash.

• A rare neurological adverse effect called reversible posterior leukoencephalopathy syndrome (RPLS) has been associated with treatment with Aybintio. If you have headaches, vision changes, confusion, or seizures (convulsions) with or without high blood pressure, consult your doctor.

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

Before starting treatment with Aybintio or during treatment with Aybintio:

• If you have or have had mouth pain, teeth, and/or jaw pain, swelling, or sores in the mouth, numbness, or a feeling of heaviness in the jaw, or tooth loss, inform your doctor and dentist immediately.
• If you need to undergo invasive dental treatment or surgery, inform your dentist that you are being treated with Aybintio, especially when you are also receiving or have received bisphosphonates in your blood.

You may be advised to have a dental check-up before starting treatment with Aybintio.

Children and Adolescents

Aybintio is not recommended for use in children and adolescents under 18 years old as its safety and efficacy have not been established in these patients.

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

Other Medications and Aybintio

Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication.

The combination of Aybintio with another medication called sunitinib malate (prescribed for renal and gastrointestinal cancer) may cause severe adverse effects. Consult your doctor to ensure that you do not combine these medications.

Consult your doctor if you are receiving platinum-based or taxane-based chemotherapy for metastatic breast or lung cancer. These therapies in combination with Aybintio may increase the risk of severe adverse effects.

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

Pregnancy, Breastfeeding, and Fertility

You should not use this medication if you are pregnant. Aybintio may harm the fetus, as it may slow down the formation of new blood vessels. Your doctor should advise you to use a contraceptive method during treatment with Aybintio and at least 6 months after the last dose of Aybintio.

Inform your doctor immediately if you are already pregnant, become pregnant during treatment with this medication, or intend to become pregnant.

You should not breastfeed your baby during treatment with Aybintio and at least 6 months after the last dose of Aybintio, as this medication may interfere with your baby's growth and development.

Aybintio may affect female fertility. Consult your doctor for more information.

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

Driving and Operating Machines

Aybintio has not been observed to decrease your ability to drive or operate tools or machines. However, drowsiness and fainting have been reported with the use of Aybintio. If you experience symptoms that affect your vision or concentration, or your reaction time, do not drive or operate machines until the symptoms disappear.

Important Information about Some Components of Aybintio

This medication contains less than 1 mmol of sodium (23 mg) per vial, which is essentially "sodium-free".

Dosage and Administration Frequency

The dose of Aybintio required 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 the most suitable dose of Aybintio for your case, and you will be treated with Aybintio once every 2 or 3 weeks. The number of infusions you receive will depend on how you respond to treatment and you should continue it until Aybintio can no longer stop tumor growth. Your doctor will discuss these aspects with you.

Form and Route of Administration

Do not shake the vial. Aybintio is a concentrate for solution for infusion. Depending on the dose prescribed, a fraction or the entire contents of the Aybintio vial will be diluted with sodium chloride solution before administration. A doctor or nurse will administer this diluted Aybintio solution as intravenous infusion (drip in your veins). The first infusion will be administered over 90 minutes. If you tolerate this infusion well, the second can be administered over 60 minutes. Subsequent infusions can be administered over 30 minutes.

Aybintio Administration Must Be Temporarily Interrupted:

• if you develop severe hypertension requiring treatment with antihypertensive medications,
• if you have wound healing problems after surgery,
• if you have undergone surgery.

Aybintio Administration Must Be Permanently Suspended If You Have:

• severe hypertension that cannot be controlled with antihypertensive medications; or in the event of a sudden and severe increase in blood pressure,
• protein in the urine accompanied by body swelling,
• a perforation in the intestinal wall,
• an abnormal communication of a tubular or fistulous type between the trachea and esophagus (the passage 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 (fistula), and which your doctor considers severe,
• severe skin or deep skin layer infections,
• arterial embolism (blood clot),
• pulmonary vein embolism,
• any severe hemorrhage.

If You Use More Aybintio Than You Should

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

If You Forget to Use Aybintio

• Your doctor will decide when the next dose of Aybintio should be administered. You must inform your doctor of this oversight.

If You Interrupt Treatment with Aybintio

Stopping treatment with Aybintio may suppress its effect on tumor growth.

Do not stop treatment with Aybintio unless you have consulted with your doctor.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

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

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 skin redness or flushing, rashes, chills, and tremors, dizziness or nausea, swelling, dizziness, tachycardia, loss of consciousness.

You must seek immediate help if you experience any of the following side effects.

Severe side effects that may bevery common(may affect more than 1 in 10 patients) include:

• high blood pressure,
• sensation 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 to clot,
• sensation of weakness and lack of energy,
• fatigue,
• diarrhea, nausea, vomiting, and abdominal pain.

Severe side effects that may becommon(may affect up to 1 in 100 patients) include:

• intestinal perforation,
• bleeding, including hemoptysis in patients with non-small cell lung cancer,
• embolism of arteries,
• embolism of veins,
• embolism of pulmonary arteries,
• embolism of leg veins,
• heart failure,
• problems with wound healing after surgery,
• redness, peeling, sensitivity, pain, or blisters on fingers or feet,
• decrease in the number of red blood cells,
• lack of energy,
• gastrointestinal and intestinal alterations,
• muscle and joint pain, muscle weakness,
• dry mouth combined with thirst and/or reduced urine output or dark urine,
• inflammation of the mucous membrane of the mouth and intestines, lungs, and airways, reproductive system, and urinary tract,
• mouth sores and esophageal tube that may be painful and cause difficulty swallowing,
• pain, including headache, back pain, pelvic pain, and anal pain,
• localized pus foci,
• infection, and particularly blood infection or urinary tract infection,
• decrease in cerebral blood flow or apoplexy,
• drowsiness,
• nasal bleeding,
• increased heart rate (pulse),
• intestinal obstruction,
• abnormal urine test (proteins in urine),
• difficulty breathing or decreased oxygen levels in blood,
• skin infections or infections of deeper layers under the skin,
• fistula: abnormal communication of tubular type between internal organs and skin or other tissues that are normally not connected, including communication between vagina and intestine in patients with cervical cancer,

?allergic reactions (the signs may include difficulty breathing, facial redness, skin rash, low blood pressure or high blood pressure, low oxygen levels in blood, chest pain or nausea/vomiting),

Severe side effects that may berare(may affect up to 1 in 1000 patients) include:

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

Severe side effects of unknown frequency(cannot be estimated from available data) include:

• serious skin infections or infections of deeper layers under the skin, especially if you had intestinal perforations or problems with wound healing,
• negative effect on the woman's ability to have children (see below for more recommendations),
• brain disease with symptoms such as seizures (attacks), headache, confusion, and visual disturbances (Reversible Posterior Leukoencephalopathy Syndrome or RPLS),
• symptoms suggesting changes in normal brain function (headache, visual disturbances, confusion, or seizures), and high blood pressure,
• increase and weakening of the wall of a blood vessel or tearing of the wall of a blood vessel (aneurysms and arterial dissections).
• obstruction 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 cartilage wall that separates the nasal openings,
• perforation in the stomach or intestine,
• ulcer or perforation in the stomach or small intestine lining (these signs may include abdominal pain, sensation of swelling, black stools, stools with blood, 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 more recommendations, see below the list of side effects),
• perforation of the gallbladder (the symptoms and signs may include abdominal pain, fever, nausea, and vomiting).

If you experience any of these side effects mentioned, seek medical attention as soon as possible.

Side effectsvery common(may affect up to 1 in 10 patients) that were not severe are:

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

Side effectscommon(may affect up to 1 in 100 patients) that were not severe are:

• voice changes and hoarseness.

Patients over 65 years old have a higher risk of experiencing the following:

• embolism in arteries that may cause apoplexy or heart attack,
• decrease in the number of white blood cells and platelets (which help to clot) in blood,
• diarrhea,
• unwellness,
• headache,
• fatigue,
• high blood pressure.

Aybintio may also cause changes in laboratory tests that your doctor will perform. These changes may include a decrease in the number of white blood cells, particularly neutrophils (a type of white blood cell that facilitates protection against infections), presence of proteins in urine, decrease in potassium, sodium, or phosphorus in blood, increase in blood sugar, increase in alkaline phosphatase (an enzyme) in blood, decrease in hemoglobin (which is found in red blood cells and transports oxygen), which may be severe.

Pain in the mouth, teeth, and/or jaw, swelling, or sores in the mouth, numbness or heaviness of 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 them.

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

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

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

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label after EXP. The expiration date is the last day of the month indicated.

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

Do not freeze.

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

The unopened vial can be stored at temperatures not exceeding 30°C for a maximum of 35 days. The vial must be discarded if it is not used within 35 days once removed from the refrigerator, even if it has been returned to the refrigerator during this period.

The infusion solution must be administered immediately after dilution. If it is not administered immediately, the storage times and conditions in use are the responsibility of the user and are normally not more than 24 hours at between 2°C and 8°C, unless the infusion solutions have been prepared in a sterile environment. When the dilution has taken place in a sterile environment, Abyntio is stable for 45 days at between 2°C and 8°C plus an additional 72 hours at temperatures not exceeding 30°C.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Aybintio

The active ingredient is bevacizumab.

?Each milliliter of concentrate contains 25mg of bevacizumab,

Each vial of 4ml contains 100mg of bevacizumab, corresponding to 1.4mg/ml when diluted as recommended.

Each vial of 16ml contains 400mg of bevacizumab, corresponding to 16.5mg/ml when diluted as recommended.

?The other components are trehalose dihydrate, sodium acetate trihydrate, acetic acid, polisorbate 20, and water for injection (see section2).

Appearance of the product and contents of the package

Aybintio is a concentrate for solution for infusion. The concentrate is a transparent, colorless to pale brown liquid contained in a glass vial with a rubber stopper. Each vial contains either 100mg of bevacizumab in 4ml of solution or 400mg of bevacizumab in 16ml of solution. Each package of Aybintio contains one vial.

Marketing Authorization Holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

[email protected]

Responsible for manufacturing

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

To obtain more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of the summary of product characteristics:

Other sources of information

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

This summary of product characteristics can be found on the website of the European Medicines Agency in all languages of the European Union/European Economic Area.