Bavencio 20 mg/ml concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Bavencio 20 mg/ml concentrate for solution for infusion

avelumab

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.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Bavencio is and what it is 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 tumour cells and helps protect them from the immune system (the body's natural defences). Bavencio binds to PD-L1 and blocks this protective effect, allowing the immune system to attack tumour 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 tract, 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 tumour has not grown after platinum-based chemotherapy as initial 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 must be used in combination with axitinib.

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

2. What you need to know before starting Bavencio

Do not use Bavencio

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

Warnings and precautions

Blood tests and weight monitoring

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

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

Talk to your doctor before starting Bavencio

It may cause adverse effects (see section 4). Be aware that these symptoms may sometimes appear with a delay and may occur after the last dose. If you experience any of the following, 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 affecting hormone-producing glands (thyroid gland, adrenal glands, and pituitary gland) that may impair their function;
• type 1 diabetes, including a serious, sometimes potentially life-threatening condition caused by acid in the blood due to diabetes (diabetic ketoacidosis);
• kidney problems;
• inflammation of your muscles (myositis and polymyalgia rheumatica);
• problems due to inflammation of your lungs, skin, eyes, or lymph nodes (sarcoidosis);
• inflammation and fibrosis of the bile ducts (sclerosing cholangitis);
• joint inflammation (arthritis);
• inflammation of glands that produce secretions to moisten the body (Sjögren's syndrome).

If you notice any of these symptoms while taking Bavencio, do not attempt to treat them yourself with other medicines. Your doctor may

• give you other medications to prevent complications and reduce symptoms,
• delay your next dose of Bavencio,
• or permanently discontinue treatment with Bavencio.

Talk to your doctor or nurse before starting Bavencio if

• you have an autoimmune disease (a disorder in which the body attacks its own cells);
• you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS);
• you have or have ever had chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV);
• you are taking medications that suppress the immune system;
• you have received an organ transplant.

Bavencio acts on the immune system and may cause inflammation in certain parts of your body. The risk of these adverse effects may be higher if you already have an autoimmune disease (a disorder in which the body attacks its own cells). You may also experience frequent flares 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 need to take any other medicines.

Pregnancy

Bavencio may harm the unborn baby. If you are pregnant, think you might be pregnant, or plan to become pregnant, talk to your doctor before using this medicine.

Do not use Bavencio if you are pregnant unless specifically recommended by your doctor.

If you are a woman of childbearing potential, you must use effective contraception during treatment with Bavencio and for at least 1 month after the last dose.

Breastfeeding

Tell your doctor if you are breastfeeding.

Do not breastfeed while receiving Bavencio and for at least 1 month after the last dose.

It is unknown whether Bavencio passes into breast milk. The risk to the breastfed infant cannot be excluded.

Driving and use of machines

Do not drive or operate machinery after receiving Bavencio if you do not feel well enough. Fatigue is a very common adverse effect of Bavencio and may affect your ability to drive or operate machinery.

Bavencio has a low sodium content

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

Bavencio contains polysorbate

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

3. How to use Bavencio

You will receive Bavencio at 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 intravenous infusion (drip) over a period of 1 hour. Prior to use, Bavencio will be added to an infusion bag containing a sodium chloride solution.

Before receiving Bavencio

For at least the first 4 treatments, you will receive paracetamol and an antihistamine before administration of Bavencio to help prevent possible infusion-related adverse reactions. Depending on how your body responds to treatment, your doctor may decide to continue giving you these medications before all Bavencio treatments.

If you missed a dose of Bavencio

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

If you interrupt treatment with Bavencio

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

Interrupting treatment may stop the effect of the medicine.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. Some adverse effects may appear weeks or months after the last dose.

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

Seek urgent medical attention if you notice inflammation in any part of your body or if you develop any of the following signs or symptoms, or if these worsen.

• Signs of infusion-related reactions such as shortness of breath or wheezing (noises when breathing), chills or shaking, raised rash or hives, flushing, low blood pressure (dizziness, fatigue, nausea), fever, back pain, and abdominal pain. These reactions are very common.

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

• Signs of lung inflammation (pneumonitis) may include difficulty breathing or cough. These reactions are common.

• Signs of intestinal inflammation (colitis) may include diarrhea (loose stools) or more bowel movements than usual, blood in the stool or dark, tarry, sticky stools, or severe pain or tenderness when touching the stomach area (abdomen). These reactions are common.

• Signs of liver problems, including liver inflammation (hepatitis), may include yellowing of the skin (jaundice) or of the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea-colored), bleeding or bruising more easily than normal, loss of appetite, tiredness, or abnormal liver function tests. These reactions are common.

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

• Signs of heart inflammation (myocarditis) may include difficulty breathing, dizziness or fainting, fever, pain and tightness in the chest, or flu-like symptoms. These reactions are uncommon.

• Signs of type 1 diabetes, including diabetic ketoacidosis, may include increased hunger or thirst, needing to urinate more often, weight loss, and feeling tired or having difficulty thinking clearly, sweet or fruity-smelling breath, feeling sick or being sick, stomach pain, and deep or rapid breathing. These reactions are uncommon.

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

• Signs of muscle inflammation such as myositis, which may include muscle pain or weakness, and polymyalgia rheumatica, which may include muscle pain or stiffness. Myositis is uncommon; the frequency of polymyalgia rheumatica is unknown.

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

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

• Signs of inflammation and fibrosis of the bile ducts, which may include pain in the upper right side of the stomach, enlargement of the liver or spleen, fatigue, itching, or yellowing of the skin or whites of the eyes (sclerosing cholangitis). Frequency is unknown.

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

• Low neutrophil count, a type of white blood cell that helps fight infections. Frequency is unknown.

Do not attempt to treat them yourself with other medicines.

Other adverse effects

Some adverse effects may not cause symptoms and may 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 arms, feet, or legs
• Weight loss, reduced appetite

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

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

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

• Bladder inflammation. Signs and symptoms may include frequent and/or painful urination (micturition), 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
• Reduced appetite, weight loss
• Headache, dizziness
• Joint pain, back pain, abdominal pain, muscle pain
• Elevated liver enzymes in blood
• Feeling cold
• Rash, itching
• Fever

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Decreased number of a type of white blood cells (lymphocytes)
• Increased number of a type of white blood cells (eosinophils)
• Intestinal obstruction
• Myasthenia gravis, myasthenic syndrome, a disease that may 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 containing 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 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 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 the carton after CAD or 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 in the original packaging to protect from light.

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

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

6. Contents of the pack and other information

Composition of Bavencio

The active substance is avelumab.

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

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

Appearance of the product and contents of the pack

Bavencio is a sterile, clear, colourless to slightly yellow concentrate for infusion solution.

Pack size: 1 glass vial per carton.

Marketing Authorisation Holder

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

Manufacturer

Merck Serono S.p.A.
Via Delle Magnolie 15 (loc. frazione Zona Industriale)
70026 - Modugno (BA)
Italy

Date of the most recent 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.

This information is intended for healthcare professionals only:

Handling instructions

Preparation and administration

Aseptic technique must be used when preparing the infusion solution.

• Visually inspect the vial for particles and discoloration. Bavencio is a clear, colourless to slightly yellow solution. If the solution is cloudy, discoloured or contains particles, discard the vial.
• Use an appropriate-sized infusion bag (preferably 250 ml) containing either a 9 mg/ml (0.9%) sodium chloride infusion solution or a 4.5 mg/ml (0.45%) sodium chloride infusion solution. Withdraw the required volume of Bavencio from the vial(s) and transfer it to the infusion bag. Any partially used or empty vial must be discarded.
• Gently invert the bag to mix the diluted solution, avoiding foaming or excessive shear stress.
• Inspect the solution to ensure it is clear, colourless and free from visible particles. The diluted solution should be used immediately after preparation.
• Do not co-administer other medicinal products through the same intravenous line. Administer the infusion using a sterile, pyrogen-free, low-protein-binding 0.2-micron in-line filter or accessory.

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

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

Any unused medicinal product and materials that have come into contact with it must be disposed of in accordance with local regulations.