Polivy 30 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Polivy 30 mg powder for concentrate for solution for infusion

Polivy 140 mg powder for concentrate for solution for infusion

polatuzumab vedotina

This medicinal product is subject to additional monitoring, which will allow for rapid identification of new safety information. You can help by reporting any side effects you may experience. Section 4 includes information on how to report side effects.

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Leaflet contents

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

1. What Polivy is and what it is used for

What Polivy is

Polivy is a cancer medicine containing the active substance called “polatuzumab vedotin”.

This medicine is always used together with other cancer medicines; see below “Other medicines given with Polivy”.

What Polivy is used for

Polivy is given to treat “diffuse large B-cell lymphoma” that has not been treated before.

Polivy is also given to treat “diffuse large B-cell lymphoma” that has come back or has not improved:

• after at least one prior treatment, and
• when you cannot receive a stem cell transplant.

Diffuse large B-cell lymphoma is a cancer that arises from B lymphocytes, also known as B cells. These are a type of blood cell in the lymphatic system.

How Polivy works

Polivy is a “monoclonal antibody” linked to a cell-killing substance called MMAE.

? One part of the medicine’s monoclonal antibody binds to B cells.

? Once attached to the B cells, the medicine releases MMAE into the B cells and kills them.

Other medicines given with Polivy

Polivy is given in combination with other cancer medicines:

? Rituximab, cyclophosphamide, doxorubicin, and prednisone for “diffuse large B-cell lymphoma” that has not been treated before.

? Rituximab and bendamustine for “diffuse large B-cell lymphoma” that has come back or has not improved, after at least one prior treatment, and when you cannot receive a stem cell transplant.

2. What you need to know before Polivy is administered to you

Do not receive Polivy if:

• You are allergic to polatuzumab vedotin or to any of the other ingredients of this medicine (listed in section 6).
• You have an active severe infection.

If either of these applies to you, you must not receive Polivy. If you are unsure, contact your doctor or nurse before receiving Polivy.

Warnings and precautions

Talk to your doctor or nurse before receiving Polivy if:

• You have ever had brain or nerve problems such as:
  • memory problems
  • difficulties moving or sensing sensations in your body, such as tingling, burning, pain, or discomfort even with light touch
  • vision problems
• You have ever had liver problems
• You think you may currently have an infection or have had persistent or repeated infections (see “Infections” in section 4)
• You are due to receive a vaccine or know you may need one in the near future

If any of the above apply to you (or if you are unsure), consult your doctor or nurse before receiving Polivy.

Pay attention to the following adverse effects

Polivy may cause some serious adverse effects that you must report immediately to your doctor or nurse. These include:

Myelosuppression

Myelosuppression is a condition in which the production of normal blood cells is reduced, resulting in lower numbers of red blood cells, white blood cells, and platelets. Your doctor will perform blood tests to monitor your blood cell counts.

Immediately report to your doctor or nursing staff if:

• You have chills or shivering
• You have a fever
• You have headaches
• You feel tired
• You experience dizziness
• You look pale
• You have unusual bleeding, bruising under the skin, prolonged bleeding after a blood draw, or bleeding from the gums

Peripheral neuropathy

Immediately report to your doctor or nursing staff if you experience any changes in skin sensation, especially in your hands or feet, such as:

• Numbness
• Tingling
• Burning sensation
• Pain
• Discomfort or weakness
• Difficulty walking

If you experienced any of these symptoms before starting treatment with Polivy, inform your doctor immediately, as well as if you notice any changes in these symptoms.

If you develop symptoms of peripheral neuropathy, your doctor may reduce your dose.

Infections

Signs and symptoms of infections vary among individuals; immediately report to your doctor or nursing staff if you develop symptoms of an infection, such as:

• Fever
• Cough
• Chest pain
• Fatigue
• Painful skin rash
• Sore throat
• Burning/pain when urinating
• Feeling weak or generally unwell

Progressive multifocal leukoencephalopathy (also called PML)

PML is a very rare and potentially fatal brain infection that has been reported in one patient receiving Polivy in combination with bendamustine and another medicine called obinutuzumab.

Immediately report to your doctor or nursing staff if you experience:

• Memory loss
• Difficulty speaking
• Difficulty walking
• Vision problems

If you experienced any of these symptoms before treatment with Polivy, inform your doctor immediately if you notice any changes in them. You may require medical treatment.

Tumor lysis syndrome

Some people may develop abnormal levels of certain chemicals in the blood (such as potassium and uric acid) due to the rapid breakdown of cancer cells during treatment. This is called "tumor lysis syndrome." Your doctor, pharmacist, or nurse will perform blood tests to monitor your condition.

Infusion-related reactions

Infusion-related reactions, allergic reactions, or anaphylactic reactions (more severe allergies) may occur. Your doctor or nurse will monitor for side effects during the infusion and for 30 to 90 minutes afterward. If you have a serious reaction, your doctor may discontinue treatment with Polivy.

Hepatotoxicity

This medicine may cause inflammation or damage to liver cells, which may affect normal liver function. This can be detected because damaged liver cells may release higher-than-normal amounts of certain substances (liver enzymes and bilirubin) into the bloodstream, leading to elevated levels in blood tests.

In most cases, no symptoms occur, but immediately inform your doctor and nurse if you experience:

• Yellowing of the skin or whites of the eyes (jaundice)

Your doctor will perform blood tests to check your liver function before and regularly during treatment.

Children and adolescents

This medicine should not be used in children or adolescents under 18 years of age. This is because there is no information on its use in this age group.

Other medicines and Polivy

Other medicines and vaccines

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription and herbal remedies.

Also inform your doctor or nurse if you are due to be vaccinated or know you may need vaccination in the near future.

Contraception (men and women)

Women of childbearing potential must use effective contraceptive methods during treatment and for 9 months after the last dose of Polivy.

Men must use contraceptive methods during treatment and for 6 months after the last dose of Polivy.

Pregnancy

It is important to inform your doctor before and during treatment if you are pregnant, think you may be pregnant, or intend to become pregnant. This is because Polivy may affect your baby's health.

Do not use this medicine during pregnancy unless you and your doctor decide that the benefits outweigh the potential risks to the fetus.

Breastfeeding

You must not breastfeed while receiving Polivy and for at least 3 months after the last dose, as a small amount of Polivy may pass into breast milk.

Fertility

Men are advised to have sperm samples frozen and stored before starting treatment with this medicine.

Driving and using machines

Polivy may slightly affect your ability to drive, ride a bicycle, or operate tools or machinery. If you experience infusion-related reactions, nerve damage, or feel tired, weak, or dizzy (see section 4), you should not drive, ride a bicycle, or use tools or machinery until the reaction has resolved.

See section 4 for more information about these effects.

Polivy contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., it is essentially "sodium-free."

Polivy contains polysorbates

Polivy 30 mg contains 1.8 mg of polysorbate 20 per vial. Polivy 140 mg contains 8.4 mg of polysorbate 20 per vial, equivalent to 1.2 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Polivy is administered

Polivy is administered under the supervision of a physician experienced in the administration of this type of treatment.

It is given intravenously as an infusion over 90 minutes.

What dose of Polivy is administered

The dose of this medicine depends on your body weight.

• The initial dose of this medicine is 1.8 mg per kilogram of body weight.
• If you have symptoms of peripheral neuropathy, your doctor may reduce your dose.

How often Polivy is administered

• Each cycle lasts 21 days.
• You will receive 6 cycles of Polivy treatment in combination with other medicines.

With which other medicines Polivy is administered

? rituximab, cyclophosphamide, doxorubicin, and prednisone for previously untreated “diffuse large B-cell lymphoma”

? rituximab and bendamustine for “diffuse large B-cell lymphoma” that has relapsed or did not improve after at least one prior treatment—and when you are not eligible for stem cell transplant.

If you miss a dose of Polivy

If you miss your appointment, schedule another one as soon as possible. To ensure the treatment is fully effective, it is very important not to miss any doses.

If you interrupt treatment with Polivy

Do not stop using Polivy unless you have discussed it with your doctor. This is because interrupting treatment could halt the medicine’s effect.

If you have further questions about the use of this medicine, please contact your doctor or nurse.

4. Possible adverse effects

Like all medicines, this one may cause adverse effects, although not everyone experiences them. The following adverse effects have been reported with this medicine:

Serious adverse effects

Inform your doctor or nurse immediately if you notice any of the following serious adverse effects, as you may require urgent medical treatment. These may be new symptoms or a change in your current symptoms.

• infusion-related reactions: your doctor will monitor you for these for 30–90 minutes after

• fever and chills

• rash/hives

• serious infections

• pneumonia (lung infection)

• herpes infection

• viral infections

• upper respiratory tract infection

• skin infection

• lower urinary tract infection

• abnormal bleeding or bruising under the skin

• memory loss, difficulty speaking, difficulty walking, or vision problems

• yellowing of the skin or whites of the eyes (jaundice)

• shortness of breath and difficulty breathing

Other side effects:

Inform your doctor or nurse if you notice any of the following side effects:

Very common: may affect more than 1 in 10 people:

• pneumonia (lung infections)
• runny nose, sneezing, sore throat, and cough (upper respiratory tract infection)
• numbness, tingling, burning sensation, pain, discomfort, or weakness and/or difficulty walking (peripheral neuropathy)
• fever
• cough
• vomiting
• diarrhea or constipation
• pain or inflammation of the mouth and/or intestine (mucositis)
• malaise (nausea)
• abdominal (stomach) pain
• fatigue
• loss of appetite
• weight loss
• infusion-related reactions
• common cold
• hair loss
• changes in blood tests:

? low levels of all types of white blood cells (combined)

? low levels of neutrophils (a type of white blood cell), with or without fever

? low platelet count (a type of blood cell that helps blood to clot)

? low red blood cell count (anemia)

? low potassium levels in the blood (hypokalemia)

Common: may affect up to 1 in 10 people

• serious infection (sepsis)

• urinary tract infection

• viral infections

• herpes infection

• skin infection

• lung inflammation

• shortness of breath and difficulty breathing

• dizziness

• fluid retention causing swelling in the lower legs or hands (peripheral edema)

• high levels of transaminase in the blood

• joint pain

• itching

• chills

• rash

• dry skin

• muscle pain

• changes in blood tests:

• decrease in all types of blood cells (pancytopenia)

• low lymphocyte count (a type of white blood cell)

• low phosphate levels in the blood (hypophosphatemia)

• low calcium levels in the blood (hypocalcemia)

• low albumin levels in the blood (hypoalbuminemia)
  ? high levels of lipase enzyme in the blood)

Uncommon: may affect up to 1 in 100 people

• blurred vision

Inform your doctor or nurse immediately if you notice any of the adverse effects listed above.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Polivy

Polivy will be stored by healthcare professionals at the hospital or clinic. The storage instructions are as follows:

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (2°C – 8°C).
• Do not freeze.
• Keep the container in the outer packaging to protect it from light.

Medicines must not be disposed of via wastewater or household waste. Your healthcare professional will dispose of any unused medicines properly. This helps protect the environment.

6. Contents of the container and other information

Composition of Polivy

• The active substance is polatuzumab vedotin.
• Polivy 30 mg: each vial contains 30 milligrams (mg) of polatuzumab vedotin.
• Polivy 140 mg: each vial contains 140 milligrams (mg) of polatuzumab vedotin.
• After each reconstitution, each milliliter (ml) contains 20 mg of polatuzumab vedotin.
• The other components are succinic acid, sodium hydroxide, sucrose, and polysorbate 20. See section 2 “Polivy contains sodium and polysorbates.”

Appearance of Polivy and contents of the container

Polivy powder for concentrate for solution for infusion is a white to slightly greyish-white powder contained in a glass vial.

Each Polivy pack contains one vial.

Marketing Authorization Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium N.V. Roche S.A. Tel/Tel.: +32 (0) 2 525 82 11	Lithuania UAB “Roche Lietuva” Tel.: +370 5 2546799
Bulgaria Roche Bulgaria EOOD Tel.: +359 2 818 44 44	Luxembourg/Luxembourg (See/see Belgium/Belgium)
Czech Republic Roche s. r.o. Tel.: +420 ‑ 2 20382111	Hungary Roche (Hungary) Kft. Tel: +36 ‑ 23 446 800
Denmark Roche Pharmaceuticals A/S Tel.: +45 ‑ 36 39 99 99	Malta Refer to Ireland
Germany Roche Pharma AG Tel.: +49 (0) 7624 140	Netherlands Roche Nederland B.V. Tel.: +31 (0) 348 438050
Estonia Roche Eesti OÜ Tel.: +372 ‑ 6 177 380	Norway Roche Norge AS Tel.: +47 ‑ 22 78 90 00
Greece Roche (Hellas) A.E. Tel.: +30 210 61 66 100	Austria Roche Austria GmbH Tel.: +43 (0) 1 27739
Spain Roche Farma S.A. Tel.: +34 ‑ 91 324 81 00	Poland Roche Polska Sp.z o.o. Tel.: +48 ‑ 22 345 18 88
France Roche Tel.: +33 (0) 1 47 61 40 00	Portugal Roche Farmacêutica Química, Lda Tel: +351 ‑ 21 425 70 00
Croatia Roche d.o.o. Tel.: +385 1 4722 333 Ireland Roche Products (Ireland) Ltd. Tel.: +353 (0) 1 469 0700	Romania Roche România S.R.L. Tel.: +40 21 206 47 01 Slovenia Roche farmacevtska družba d.o.o. Tel.: +386 ‑ 1 360 26 00
Iceland Roche Pharmaceuticals A/S c/o Icepharma hf Tel.: +354 540 8000	Slovakia Roche Slovensko, s.r.o. Tel.: +421 ‑ 2 52638201
Italy Roche S.p.A. Tel.: +39 ‑ 039 2471	Finland Roche Oy Tel./Puh.: +358 (0) 10 554 500
Cyprus G.A. Stamatēs & Sia Ltd. Tel.: +357 ‑ 22 76 62 76	Sweden Roche AB Tel.: +46 (0) 8 726 1200
Latvia Roche Latvija SIA Tel.: +371 ‑ 6 7039831	United Kingdom (Northern Ireland) Roche Products (Ireland) Ltd. Tel.: +44 (0) 1707 366000

Date of the most recent review of this leaflet:

Other sources of information

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

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Information intended only for healthcare professionals:

Appropriate procedures for handling and disposal of anticancer drugs should be followed.

Reconstitution instructions

? Polivy 30 mg: Using a sterile syringe, slowly inject 1.8 ml of sterile water for injection into the 30 mg Polivy vial to obtain a single-dose solution containing 20 mg/ml of polatuzumab vedotin. Direct the stream onto the vial wall and not directly onto the lyophilized powder.

? Polivy 140 mg: Using a sterile syringe, slowly inject 7.2 ml of sterile water for injection into the 140 mg Polivy vial to obtain a single-dose solution containing 20 mg/ml of polatuzumab vedotin. Direct the stream onto the vial wall and not directly onto the lyophilized powder.

? Gently rotate the vial until the powder is completely dissolved. Do not shake.

? Inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be colorless to slightly brown, clear to slightly opalescent, and free of visible particles. The reconstituted solution must not be used if it has changed color, is cloudy, or contains visible particles.

Dilution instructions

1. Polivy must be diluted to a final concentration of 0.72–2.7 mg/ml in an intravenous infusion bag with a minimum volume of 50 ml, containing either 9 mg/ml sodium chloride solution for injection, 4.5 mg/ml sodium chloride solution for injection, or 5% glucose solution.
2. Determine the volume of reconstituted solution at 20 mg/ml required based on the needed dose (see below):

Total Polivy dose (mL) to be diluted later =	Polivy dose (mg/kg) × patient weight (kg)
Reconstituted vial concentration (20 mg/mL)

1. Using a sterile syringe, withdraw the appropriate amount of reconstituted solution from the Polivy vial and add it to the intravenous infusion bag. Discard any unused medicinal product remaining in the vial.
2. To mix the solution, gently invert the bag. Do not shake.
3. Inspect the intravenous bag and discard if particulate matter is present.

Reconstituted solution

From a microbiological standpoint, the reconstituted solution should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours under refrigerated conditions (2°C–8°C), unless reconstitution was carried out under controlled and validated aseptic conditions. Chemical and physical stability during use of the reconstituted solution has been demonstrated for up to 72 hours under refrigerated conditions (2°C–8°C) and up to 24 hours at room temperature (9°C–25°C).

Diluted solution

From a microbiological standpoint, the solution prepared for infusion should be used immediately. If not used immediately, the storage time prior to use and the conditions before use are the responsibility of the user and should not exceed 24 hours under refrigerated conditions (2°C–8°C), unless dilution was performed under controlled and validated aseptic conditions. Acceptable chemical and physical stability of the solution prepared for infusion has been demonstrated for the durations shown in Table 1. The diluted Polivy solution must be discarded if the storage time exceeds the limits indicated in Table 1.

Table 1 Durations for which physical and chemical stability of the solution prepared for infusion has been demonstrated

Diluent used to prepare the infusion solution	Storage conditions of the infusion solution1
Sodium chloride 9 mg/ml (0.9%)	Up to 72 hours refrigerated (2°C-8°C) or up to 4 hours at room temperature (9°C-25°C)
Sodium chloride 4.5 mg/ml (0.45%)	Up to 72 hours refrigerated (2°C to 8°C) or up to 8 hours at room temperature (9°C-25°C)
5% Glucose	Up to 72 hours refrigerated (2°C-8°C) or up to 8 hours at room temperature (9°C to 25°C)

1 To ensure product stability, do not exceed the specified storage durations.