Prospect: information for theuser

Oyavas 25mg/ml concentrate for solution for infusion

bevacizumab

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section4 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 section4.

1.What is Oyavas and how is it used

2.What you need to know before starting to use Oyavas

3.How to use Oyavas

4.Possible adverse effects

5.Storage of Oyavas

6.Contents of the package and additional information

The active principle of Oyavas 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 in 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.

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

Oyavas is also used for the treatment ofadult patients with metastatic breast cancer. When used inpatients with breast cancer, it will be administered with a chemotherapy medication called paclitaxel or capecitabine.

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

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

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

Oyavas is also used for the treatment ofadult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. When used inpatients 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 6months since their last treatment with a platinum-based chemotherapy regimen, Oyavas 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 6months since their last treatment with a platinum-based chemotherapy regimen, Oyavas will be administered in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin.

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

No use Oyavas

• 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 Oyavas.

• Oyavas 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.

• Oyavas 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.

• Oyavas 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.

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

• Oyavas 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 Oyavas.

• 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 proteins 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, have diabetes, or have had thrombi or clots in your arteries in the past. Consult your doctor, as thrombi or clots can cause heart attack and stroke.

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

• Oyavas may cause bleeding, especially bleeding related to the tumor. 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.

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

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

• Oyavas 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.

• Oyavas may cause infections and decrease the number of neutrophils (a type of blood cell important for your protection against bacteria).

• Oyavas 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 Oyavas. If you have headaches, vision changes, confusion, or seizures (convulsions) with or without high blood pressure, consult your doctor.

• Cases of bone death (osteonecrosis) in bones other than the jaw have been reported in patients under 18 years old treated with Oyavas. Pain in the mouth, teeth, and/or jaw, swelling, or sores in the mouth, numbness, or a feeling of heaviness in the jaw, or tooth loss. These may be signs and symptoms of jaw bone damage (osteonecrosis). Immediately inform your doctor and dentist if you experience any of them.

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

Before starting treatment with Oyavas or during treatment with Oyavas:

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

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

Oyavas 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 Oyavas is injected directly into the eye (unauthorized use), the following adverse effects may occur:

Children and Adolescents

Oyavas 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.

Other Medications and Oyavas

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

The combination of Oyavas 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 cancer treatment for metastatic breast or lung cancer. These treatments combined with Oyavas 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 Oyavas if you are pregnant. Oyavas may harm the fetus, as it may inhibit the formation of new blood vessels. Your doctor should advise you to use a contraceptive method during treatment with Oyavas and for at least 6 months after the last dose of Oyavas.

If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

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

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

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

Driving and Operating Machines

Oyavas 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 Oyavas. If you experience symptoms that affect your vision or concentration, or your reaction time, do not drive or operate machines until the symptoms disappear.

Oyavas Contains Sodium

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 Oyavas required depends on your weight and the type of cancer being treated. The recommended dose is 5mg, 7.5mg, 10mg or 15mg per kilogram of body weight. Your doctor will prescribe the most suitable dose of Oyavas for your case, and you will be treated with Oyavas once every 2 or 3weeks. The number of infusions you receive will depend on how you respond to treatment and you should continue until Oyavas can no longer stop tumor growth. Your doctor will discuss these aspects with you.

Form and Route of Administration

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

Oyavas 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.

Oyavas Administration Must Be Permanently Suspended If You Have:

• severe hypertension that cannot be controlled with antihypertensive medications; or in case of a sudden and severe increase in blood pressure,
• protein in the urine accompanied by body swelling,
• an intestinal wall perforation,
• an abnormal communication of a tubular or fistulous type between the trachea and esophagus (esophageal conduit), 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 bleeding.

If You Use More Oyavas Than You Should

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

If You Forget to Use Oyavas

• Your doctor will decide when the next dose of Oyavas should be administered. Inform your doctor of this omission.

If You Interrupt Treatment with Oyavas

Stopping treatment with Oyavas may suppress its effect on tumor growth. Do not stop treatment with Oyavas unless you have consulted with your doctor.

If you have any other questions 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.

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

Allergic reactions

If you have an allergic reaction, consult your doctor or healthcare professional immediately. Symptoms may include: difficulty breathing or chest pain. You may also experience skin redness or flushing, rash, chills, and tremors, feeling of dizziness (nausea) or feeling unwell (vomiting), 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 10patients) include:

Severe side effects that may becommon(may affect up to 1 in 10patients) include:

• allergic reactions (symptoms may include difficulty breathing, facial flushing, skin rash, low blood pressure or high blood pressure, low oxygen levels in the blood, chest pain or nausea/vomiting),
• • intestinal perforation,
  • bleeding, including pulmonary hemorrhage inpatients with non-small cell lung cancer,
  • arterial embolism,
  • venous embolism,
  • embolism of pulmonary vessels,
  • embolism of leg veins,
  • heart failure,
  • problems with wound healing after surgery,
  • erythema, desquamation, sensitivity, pain, or blisters on fingers or toes,
  • 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-colored urine,
  • inflammation of the mucous membrane of the mouth, intestines, lungs, and airways, reproductive system, and urinary tract,
  • mouth and esophageal ulcers, which may be painful and cause difficulty swallowing,
  • pain, including headache, back pain, pelvic pain, and anal pain,
  • localized pus-filled areas,
  • infection, and particularly blood infection or urinary tract infection,
  • decrease in blood flow to the brain or stroke,
  • drowsiness,
  • nosebleed,
  • increased heart rate (pulse),
  • intestinal obstruction,
  • abnormal urine test (protein in urine),
  • difficulty breathing or decreased oxygen levels in the blood,
  • skin or deep tissue infections,
  • fistula: abnormal communication between internal organs and the skin or other tissues that are normally not connected, including communication between the vagina and the intestine inpatients with cervical cancer.

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:

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

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

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

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

Oyavas 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 helps to protect against infections), presence of protein 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.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a side effect that does not appear in this prospectus. You can also report them directly throughthe national 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 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 between 2 °C and 8 °C, unless the infusion solutions have been prepared in a sterile environment. When dilution takes place in a sterile environment, Oyavas will remain stable after dilution for a period of up to 30 days stored between 2 °C and 8 °C and for a period of up to 48 hours at temperatures not exceeding 30 °C.

Do not use Oyavas 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 the medication that you no longer need. This will help protect the environment.

Composition of Oyavas

• The active principle is bevacizumab. Each milliliter of concentrate contains 25mg of bevacizumab, corresponding to 1.4 or 16.5mg/ml when diluted as recommended.
• Each vial of 4 ml contains 100mg of bevacizumab, corresponding to 1.4mg/ml when diluted as recommended.
• Each vial of 16 ml contains 400mg of bevacizumab, corresponding to 16.5mg/ml when diluted as recommended.
• The other components are trehalose dihydrate, sodium phosphate monobasic monohydrate, disodium phosphate, polisorbate 20, and water for injection (see section2 “Oyavas contains sodium”).

Appearance of the product and contents of the package

Oyavas is a concentrate for solution for infusion (sterile concentrate). The concentrate is a colorless to brown or pale yellow liquid with opalescence contained in a glass vial with a rubber stopper. Each vial contains 100mg of bevacizumab in 4ml of solution or 400mg of bevacizumab in 16 ml of solution. Each package of Oyavas contains one vial.

Marketing Authorization Holder

STADA Arzneimittel AG

Stadastrasse 2‑18

61118 Bad Vilbel

Germany

Responsible Person

GH GENHELIX S.A.

Parque Tecnológico de León

Edificio GENHELIX

C/ Julia Morros, s/n

Armunia, 24009 León, Spain

or

STADA Arzneimittel AG

Stadastrasse 2‑18

61118 Bad Vilbel

Germany

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

Last review date of this leaflet: <{MM/AAAA}>.

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:https://www.ema.europa.eu.