BAVENCIO 20 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

Bavencio 20 mg/ml concentrate for solution for infusion

avelumab

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 further questions, ask your doctor.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Bavencio and what is it used for

Bavencio contains the active substance avelumab, a monoclonal antibody (a type of protein) that binds to a specific target in the body called PD-L1.

PD-L1 is found on the surface of certain cancer cells and helps protect them from the immune system (the body's natural defenses). Bavencio binds to PD-L1 and blocks this protective effect, allowing the immune system to attack the cancer cells.

Bavencio is used in adults to treat:

• Merkel cell carcinoma (MCC), a rare type of skin cancer, when it is metastatic (has spread to other parts of the body).
• Urothelial carcinoma (UC), a cancer that originates in the urinary system, when it is advanced or metastatic (has spread beyond the urinary bladder or to other parts of the body). Bavencio is used as maintenance treatment if the tumor has not grown after platinum-based chemotherapy as first treatment.
• Renal cell carcinoma (RCC), a type of kidney cancer, when it is advanced (has spread beyond the kidney or to other parts of the body).

For kidney cancer, Bavencio should be used in combination with axitinib.

It is also important that you read the package leaflet of the medicine that contains axitinib and consult your doctor if you have any questions.

2. What you need to know before you use Bavencio

Do not use Bavencio

if you are allergic to avelumab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Blood tests and weight checks

Your doctor will check your general health before and during treatment with Bavencio.

You will have blood tests during treatment and your doctor will check your weight before and during treatment.

Talk to your doctor before you start receiving Bavencio

It can cause side effects (see section 4). Note that these symptoms sometimes occur with delay and may appear after the last dose. If you experience any of them, you must seek urgent medical attention:

• infusion-related reactions;
• problems due to inflammation of your lungs (pneumonitis);
• inflammation of your liver (hepatitis) or other liver problems;
• inflammation of your intestines (colitis), diarrhea (watery, loose, or soft stools) or more bowel movements than usual;
• inflammation of your pancreas (pancreatitis);
• inflammation of your heart (myocarditis);
• problems with your hormone-producing glands (thyroid gland, adrenal glands, and pituitary gland) that can affect their function;
• type 1 diabetes, including a serious, potentially life-threatening problem due to acid in the blood caused by diabetes (diabetic ketoacidosis);
• problems with your kidneys;
• inflammation of your muscles (myositis and polymyalgia rheumatica);
• problems due to inflammation of your lungs, skin, eyes, or lymph nodes (sarcoidosis);
• inflammation and scarring of the bile ducts (sclerosing cholangitis);
• inflammation of your joints (arthritis);
• inflammation of the glands that produce secretions that moisten the body (Sjögren's syndrome).

If you notice any of these symptoms while taking Bavencio, do nottry to treat them on your own with other medicines. Your doctor may

• give you other medicines to prevent complications and reduce symptoms,
• delay the next dose of Bavencio,
• or stop treatment with Bavencio permanently.

Talk to your doctor or nurse before you start receiving Bavencio if

• you have an autoimmune disease (a disorder in which the body attacks its own cells);

• you have a human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS);
• you have or have had a chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV);
• you are taking medicines that suppress the immune system;
• you have had an organ transplant.

Bavencio works on the immune system and can cause inflammation in some parts of your body. The risk of you getting these side effects may be higher if you already have an autoimmune disease (a disorder in which the body attacks its own cells). You may also have frequent flare-ups of your autoimmune disease, which in most cases will be mild.

Children and adolescents

Bavencio has not been studied in children and adolescents under 18 years of age. Therefore, Bavencio must not be used in children and adolescents under 18 years of age.

Other medicines and Bavencio

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

Pregnancy

Bavencio may harm your unborn baby. If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Do not use Bavencio if you are pregnant unless your doctor specifically recommends it.

If you are a woman who can become pregnant, you must use effective contraception while you are being treated with Bavencio and for at least 1 month after the last dose.

Breast-feeding

Tell your doctor if you are breast-feeding.

Do notbreast-feed while you are being treated with Bavencio and for at least 1 month after the last dose.

It is not known whether Bavencio passes into breast milk. The risk to the baby cannot be excluded.

Driving and using machines

Do notdrive or use machines after receiving Bavencio if you do not feel well enough. Fatigue is a very common side effect of Bavencio and may affect your ability to drive or use machines.

Bavencio has a low sodium content

Bavencio contains less than 1 mmol of sodium (23 mg) per 200 mg dose; this is essentially “sodium-free”.

Bavencio contains polysorbate

Bavencio contains 5 mg of polysorbate 20 per vial. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

3. How to use Bavencio

You will receive Bavencio in a hospital or clinic, under the supervision of an experienced doctor.

How much Bavencio you will receive

The recommended dose of avelumab is 800 mg every 2 weeks. Your doctor will decide how many treatments you need.

How you will receive Bavencio

You will receive Bavencio as an infusion (drip) into a vein (intravenously) over a period of 1 hour. Bavencio will be added to an infusion bag containing a sodium chloride solution before use.

Before you receive Bavencio

For at least the first 4 treatments, you will receive paracetamol and an antihistamine before Bavencio is given to help prevent possible infusion-related side effects. Depending on how your body responds to treatment, your doctor may decide to continue giving you these medicines before all Bavencio treatments.

If you miss a dose of Bavencio

It is very important that you attend all appointments to receive Bavencio. If you miss an appointment, ask your doctor when to schedule the next dose.

If you stop treatment with Bavencio

Do notstop treatment with Bavencio unless you have discussed it with your doctor.

Stopping treatment may stop the effect of the medicine.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them. Some adverse effects may appear weeks or months after the last dose.

Bavencio acts on the immune system and may cause inflammation in some parts of the body (see section 2). Inflammation can cause serious damage to the body, and some inflammatory disorders can be life-threatening and require treatment or discontinuation of Bavencio.

Seek urgent medical attention if you notice inflammation in any part of your bodyor if you experience any of the following signs or symptoms, or if they worsen.

• Signs of infusion-related reactions such as shortness of breath or wheezing (breathing sounds), chills or shivering, swollen or rash-like skin, flushing, low blood pressure(dizziness, fatigue, nausea), fever, back painand abdominal pain. These reactions are very frequent.

• Signs of inflammation of the hormone-producing glands, which can affect their function, may include extreme fatigue, rapid heartbeat, increased sweating, mood or behavior changes,such as irritability or frequent forgetfulness, feeling cold, very low blood pressure (fainting, dizziness, fatigue, nausea),weight changesor headache. These reactions are very frequent for the thyroid gland, frequent for the adrenal glands, and infrequent for the pituitary gland.

• Signs of lung inflammation (pneumonitis) may be difficulty breathingor coughing. These reactions are frequent.

• Among the signs of intestinal inflammation (colitis) are diarrhea(soft stools) or more bowel movements than usual, blood in the stool or dark, tarry, and sticky stoolsor severe painor tenderness to palpation in the stomach area (abdomen). These reactions are frequent.

• Among the signs of liver problems, including liver inflammation (hepatitis), are yellowing of the skin(jaundice) or of the white part of the eyes,nausea or severe vomiting, pain in the right side of the stomach area(abdomen), drowsiness, dark urine(tea-colored), easier bruising or bleeding than usual, decreased appetite, fatigueor abnormal liver function tests. These reactions are frequent.

• Signs of pancreas inflammation (pancreatitis) may include abdominal pain, nausea, and vomiting. These reactions are infrequent.

• Signs of heart inflammation (myocarditis) may include difficulty breathing,dizzinessor fainting, fever, painand pressure in the chestor flu-like symptoms. These reactions are infrequent.

• Signs of type 1 diabetes, including diabetic ketoacidosis, may include increased hungeror thirst, need to urinate more frequently, weight lossand feeling tiredor having trouble thinking clearly, sweet or fruity breath, feeling sickor being sick, stomach painand deep or rapid breathing. These reactions are infrequent.

• Signs of kidney inflammation may include abnormal kidney function tests, urinating less than usual, blood in the urineor swelling of the ankles. These reactions are infrequent.

• Signs of muscle inflammation such as myositis, which may include painor weaknessin the muscles, and polymyalgia rheumatica, which may include painor stiffness in the muscles. Myositis is infrequent, and the frequency of polymyalgia rheumatica is unknown.

• Signs of inflammation associated with an accumulation of inflammatory cellsin various organs and tissues, most frequently in the lungs (sarcoidosis). These reactions are infrequent.

• Signs of joint inflammation (arthritis), which may include pain, stiffness, and swellingin the joints. These are rare.

• Signs of inflammation and fibrosis of the bile ducts, which may include pain in the upper right region of the stomach, swelling of the liver or spleen, fatigue, itchingor yellowing of the skin or the white part of the eyes(sclerosing cholangitis). The frequency is unknown.

• Signs of inflammation of the glands that produce secretions that moisten the body, such as tears and saliva, which may include dry eyesand dry mouth(Sjögren's syndrome). The frequency is unknown.

• Low number of neutrophils, a type of white blood cell that helps fight infections. The frequency is unknown.

Do not attempt to treat them on your own with other medications.

Other Adverse Effects

Some adverse effects may not produce symptoms and can only be detected through blood tests.

In clinical studies with avelumab alone, the following adverse effects have been reported:

Very Common (may affect more than 1 in 10 people)

• Low red blood cell count
• Nausea, loose stools, constipation, vomiting
• Abdominal pain, back pain, joint pain
• Cough, difficulty breathing
• Feeling tired or weak
• Fever
• Swelling of the arms, feet, or legs
• Weight loss, decreased appetite

Common (may affect up to 1 in 10 people)

• Decreased number of a type of white blood cell (lymphocytes)
• Decreased number of platelets in the blood
• Increased blood pressure
• Low sodium levels
• Headache, dizziness
• Feeling cold
• Dry mouth
• Elevated liver enzymes in the blood
• Elevated pancreatic enzymes in the blood
• Rash, itching
• Muscle pain
• Flu-like illness (including feeling feverish and muscle aches)
• Numbness, tingling, weakness, burning sensation in the arms or legs

Uncommon (may affect up to 1 in 100 people)

• Redness of the skin
• Intestinal obstruction
• Red, itchy, scaly patches on the skin, dry skin
• Decreased blood pressure
• Elevated muscle enzymes in the blood
• Increased number of a type of white blood cell (eosinophils)
• Inflammation of the joints (rheumatoid arthritis)
• Myasthenia gravis, myasthenic syndrome, a disease that can cause muscle weakness

Rare (may affect up to 1 in 1,000 people)

• Inflammation of the bladder. Signs and symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, pain or pressure in the lower abdomen

In clinical studies with avelumab in combination with axitinib, the following adverse effects have been reported:

Very Common (may affect more than 1 in 10 people)

• Loose stools, nausea, constipation, vomiting
• Increased blood pressure
• Feeling tired or weak
• Hoarseness, cough, difficulty breathing
• Decreased appetite, weight loss
• Headache, dizziness
• Pain in the joints, back pain, abdominal pain, muscle pain
• Elevated liver enzymes in the blood
• Feeling cold
• Rash, itching
• Fever

Common (may affect up to 1 in 10 people)

• Red, itchy, scaly patches on the skin, acne-like rash
• Swelling of the arms, feet, or legs
• Dry mouth
• Elevated pancreatic enzymes in the blood
• Decreased kidney function
• Decreased red blood cell count
• Decreased blood pressure
• High blood sugar
• Flu-like illness (including feeling feverish and muscle aches)
• Elevated muscle enzymes in the blood
• Decreased number of platelets in the blood
• Numbness, tingling, weakness, burning sensation in the arms or legs
• Redness of the skin

Uncommon (may affect up to 1 in 100 people)

• Decreased number of a type of white blood cell (lymphocytes)
• Increased number of a type of white blood cell (eosinophils)
• Intestinal obstruction
• Myasthenia gravis, myasthenic syndrome, a disease that can cause muscle weakness

With other similar medicines, the following adverse effects have been reported:

• Absence or reduction of digestive enzymes produced by the pancreas (exocrine pancreatic insufficiency)
• Celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming foods that contain gluten)

Reporting of Adverse Effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's online system: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bavencio

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

Do not use this medicine after the expiry date stated on the vial label and carton after CAD or EXP. The expiry date is the last day of the month indicated.

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

Do not freeze.

Store in the original packaging to protect from light.

Do not store any unused portion of the concentrate or diluted infusion solution for reuse.

Disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

6. Package Contents and Additional Information

Composition of Bavencio

The active substance is avelumab.

A 10 ml vial contains 200 mg of avelumab. Each ml of concentrate contains 20 mg of avelumab.

The other ingredients are: mannitol, glacial acetic acid, polysorbate 20, sodium hydroxide, and water for injections (see section 2 "Bavencio has a low sodium content").

Appearance and Package Contents

Bavencio is a clear, colorless to slightly yellowish concentrate for solution for infusion (sterile concentrate).

The pack size is 1 glass vial per carton.

Marketing Authorization Holder

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

Netherlands

Manufacturer

Merck Serono S.p.A.

Via Delle Magnolie 15 (loc. frazione Zona Industriale)

70026 - Modugno (BA)

Italy

Date of Last Revision of this Leaflet:

03/2025

Other Sources of Information

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

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This information is intended only for healthcare professionals:

Handling Instructions

Preparation and Administration

Aseptic technique should be used for the preparation of the infusion solution.

• The vial should be inspected visually for particles and color changes. Bavencio is a clear, colorless to slightly yellowish solution. If the solution is cloudy, has changed color, or contains particles, the vial should be discarded.
• A suitable infusion bag size (preferably 250 ml) containing a 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride infusion solution should be used. The required volume of Bavencio should be withdrawn from the vial(s) and transferred to the infusion bag. Any partially used or empty vial should be discarded.
• The diluted solution should be mixed by gently inverting the bag to avoid foaming or excessive shearing of the solution.
• The solution should be inspected to ensure it is clear, colorless, and free of visible particles. The diluted solution should be used immediately after preparation.
• Do not administer other medicines concomitantly through the same intravenous line. Administer the infusion using a 0.2-micron sterile, apyrogenic, and protein-binding filter.

After administration of Bavencio, the line should be flushed with a 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride infusion solution.

Do not freeze or shake the diluted solution. If refrigerated, the diluted solution in the intravenous bags should be allowed to reach room temperature (between 20°C and 25°C) before use.

Disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.