Prospect:information for the user

Polivy 30mg powder for concentrate for solution for infusion

Polivy 140mg powder for concentrate for solution for infusion

polatuzumab vedotina

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 the entire prospect carefully before starting to use the 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 or nurse.

?If you experience adverse effects, consult your doctor or nurse, even if they are adverse effects that do not appear in this prospect. See section 4.

1.What is Polivy and what it is used for

2.What you need to know before you are given Polivy

3.How you will be given Polivy

4.Possible adverse effects

5.Storage of Polivy

6.Contents of the package and additional information

What is Polivy

Polivy is a cancer medication that contains the active ingredient called “polatuzumab vedotina”.

This medication is always used in combination with other cancer medications; see below “Other medications administered with Polivy”Other medications administered with Polivy

How is Polivy used

Polivy is administered to treat “diffuse large B-cell lymphoma” that has never been treated before.

Polivy is also administered to treat “diffuse large B-cell lymphoma” that has recurred or has not improved:

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

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

How Polivy works

Polivy is a “monoclonal antibody” and a substance that can kill cancer cells called MMAE.

?A part of the monoclonal antibody in the medication binds to B cells.

?Once bound to B cells, the medication releases MMAE in B cells and kills them

Other medications administered with Polivy

Polivy is administered in combination with other cancer medications:

?Rituximab, cyclophosphamide, doxorubicin, and prednisone for “diffuse large B-cell lymphoma” that has never been treated before

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

You should not receive Polivy if:

• You are allergic to polatuzumab vedotina or any of the other components of this medication (listed in section6).
• You have an active severe infection.

If you apply any of the above, you should not receive Polivy. If you are unsure, contact your doctor or nurse before receiving Polivy.

Warnings and precautions

Consult your doctor or nurse before receiving Polivy if:

• You have ever had brain or nervous system problems such as:
• • memory problems
  • difficulty moving or perceiving sensations in your body, such as pins and needles, burning, pain, or discomfort even with light touch
  • vision problems
• You have ever had liver problems;
• You think you may have an infection now or have had persistent or recurring infections (see “Infections” in section4).
• You are to receive a vaccine or know that you may need one in the near future.

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

Be aware of the following adverse effects

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

Myelosuppression

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

Immediately report to your doctor or nurse if you experience:

• chills or shivering;
• fever;
• headaches;
• fatigue;
• dizziness;
• paleness;
• unusual bleeding, bruises under the skin, prolonged bleeding after a blood draw, or gum bleeding.

Peripheral neuropathy

Immediately report to your doctor or nurse if you experience any problems with a change in skin sensitivity, especially in your hands or feet, such as:

• numbness
• tingling
• burning sensation
• pain
• discomfort or weakness
• difficulty walking

If you have experienced any of these symptoms before treatment with Polivy, immediately report them to your doctor, and if you notice any changes in them.

If you have peripheral neuropathy, your doctor may reduce your dose.

Infections

The signs and symptoms of infections vary among individuals; immediately report to your doctor or nurse if you develop symptoms of an infection, such as:

• fever
• cough
• chest pain
• fatigue
• painful skin rash
• sore throat
• burning or pain while urinating
• feeling weak or generally unwell.

Progressive multifocal leukoencephalopathy (also known as PML)

PML is a rare and potentially fatal brain infection that has been reported in a patient receiving treatment with Polivy, bendamustine, and another medication called obinutuzumab.

Immediately report to your doctor or nurse if you experience:

• memory loss
• difficulty speaking
• difficulty walking
• vision problems.

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

Tumor lysis syndrome

Some individuals may develop unusual levels of certain chemicals in the blood (such as potassium and uric acid) as a result of the rapid breakdown of cancer cells during treatment. This is called “tumor lysis syndrome.” Your doctor, pharmacist, or nurse will perform blood tests to check your condition.

Reactions related to infusion

Reactions related to infusion, allergic reactions, or anaphylaxis (more severe allergies) may occur. Your doctor or nurse will check for side effects during infusion and within 30 to 90 minutes after. If you experience any severe reactions, your doctor may suspend treatment with Polivy.

Hepatotoxicity

This medication may cause inflammation or damage to liver cells, affecting their normal functioning. This can be detected because damaged liver cells may cause the elimination of higher-than-normal amounts of certain substances (liver enzymes and bilirubin) into the bloodstream, resulting in increased values in blood tests.

In most cases, no symptoms are experienced, but immediately report to your doctor and nurse if you experience:

• yellowing of the skin and the white of the eyes (jaundice).

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

Children and adolescents

This medication should not be used in children or young people under 18years. This is because there is no information on its use in this age group.

Other medications and Polivy

Other medications and vaccines

Inform your doctor or nurse if you are taking, have recently taken, or may need to take any other medication. This includes over-the-counter medications and herbal remedies.

Also, inform your doctor or nurse if you need to be vaccinated or know that you may need one in the near future.

Contraception (male and female)

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

Males should use contraceptive methods during treatment and for 6months after the last administration of the Polivy dose.

Pregnancy

It is essential 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 the health of your baby.

Do not use this medication if you are pregnant, unless you and your doctor decide that the benefits outweigh the potential risks to the fetus.

Breastfeeding

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

Fertility

Males are advised to have semen samples frozen and stored before treatment with this medication.

Driving and using machines

Polivy may slightly affect your ability to drive, ride a bike, or use tools or machines. If you experience infusion-related reactions or nerve damage, or if you feel tired, weak, or dizzy (see section4), do not drive, ride a bike, or use tools or machines until the reaction stops.

See section 4 for more information about these effects.

Polivy contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose, making it essentially “sodium-free.”

Polivy contains polysorbates

Polivy 30 mgcontains 1.8mg of polysorbate20 in each vial.Polivy 140mgcontains 8.4mg of polysorbate20 in each vial, equivalent to 1.2 mg/ml.Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

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

It is administered intravenously and by infusion for 90 minutes.

What amount of Polivy is administered

The dosage of this medication depends on your body weight.

• The initial dosage of this medication is 1.8 mg per kilogram of body weight.
• If you have symptoms of peripheral neuropathy, your physician may reduce your dosage.

How often Polivy is administered

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

With what other medications Polivy is administered

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

? rituximab and bendamustine for “large B-cell lymphoma” that has recurred or has not improved after at least one previous treatment – and when you cannot receive a stem cell transplant.

What to do if a dose of Polivy is missed

If you miss an appointment, request another as soon as possible. It is very important not to miss any doses for the treatment to be fully effective.

What to do if the treatment with Polivy is interrupted

Do not stop using Polivy unless you have consulted with your physician. This is because interrupting treatment may stop the medication's effect.

If you have any further questions about the use of this medication, contact your physician or nurse.

Like all medicines, this one may cause side effects, although not everyone will experience them. The following side effects have been reported with this medication:

Severe side effects

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

• Perfusion-related reactions: your doctor will check for these during 30-90 minutes after

• Fever and chills
• Rash/urticaria
• Severe 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
• Yellow discoloration of the skin or in the white of the eyes
• Lack of air 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)
• Nasal discharge, 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
• Mouth and/or intestinal pain and inflammation (mucositis)
• Uncomfortable feeling (nausea)
• Abdominal pain
• Fatigue
• Loss of appetite
• Weight loss
• Perfusion-related reactions
• Common cold
• Hair loss
• Change in blood test results:

?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 level of platelets (a type of blood cell that helps blood clot)

?Low levels of red blood cells (anemia)

?Low level of potassium in the blood (hypokalemia)

Common: may affect up to 1 in 10 people

• Severe infection (sepsis)
• Urinary tract infection
• Viral infections
• Herpes infection
• Skin infection
• Pulmonary inflammation
• Lack of air and difficulty breathing
• Dizziness
• Peripheral edema (swelling in the lower legs or hands due to fluid retention)
• High levels of transaminase in the blood
• Joint pain
• Itching
• Chills
• Rash
• Skin dryness
• Muscle pain
• Change in blood test results:

-Decrease in all types of blood cells (pancytopenia)

-Low levels of lymphocytes (a type of white blood cell)

-Low level of phosphate in the blood (hypophosphatemia)

-Low level of calcium in the blood (hypocalcemia)

-Low level of albumin in the blood (hypoalbuminemia)

?High level of lipase enzyme in the blood)

Rare: may affect up to 1 in 100 people

• Blurred vision

Inform your doctor or nurse immediately if you notice any of the side effects mentioned above.

Reporting side effects

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

Polivy will be conserved by healthcare professionals in the hospital or clinic. The conservation details are as follows

• 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 after EXP. The expiration date is the last day of the month indicated.
• Store in refrigerator(2°C – 8°C).
• Do not freeze.
• Store the packaging in the outer packaging to protect it from light.

Medications should not be thrown down the drain or in the trash. Your healthcare professional will dispose of the medications that you will no longer use properly. In this way, you will help protect the environment.

Composition of Polivy

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

Appearance of Polivy and contents of the pack

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

Each pack of Polivy contains a 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

To find out more about this medicine, contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

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

------------------------------------------------------------------------------------------------------------------------

Information for healthcare professionals only:

Proper procedures for handling and disposal of cancer medicines should be considered.

Instructions for reconstitution

?Polivy 30 mg:using a sterile syringe, slowly inject 1.8 ml of sterile water for injections into the Polivy 30 mg vial to obtain a single-dose solution containing 20 mg/ml of polatuzumab vedotina. The flow should be directed towards the wall of the vial and not directly onto the lyophilized powder.

?Polivy 140 mg:using a sterile syringe, slowly inject 7.2 ml of sterile water for injections into the Polivy 140 mg vial to obtain a single-dose solution containing 20 mg/ml of polatuzumab vedotina. The flow should be directed towards the wall of the vial and not directly onto the lyophilized powder.

?Swirl the vial gently until the powder is completely dissolved. Do not agitate.

?Inspect the reconstituted solution for the presence of particles and color changes. The reconstituted solution should be colorless to slightly brown, transparent to slightly opalescent, and free of visible particles. The reconstituted solution should not be used if it has changed color, is turbid, or contains visible particles.

Instructions for dilution

1.Polivy should be diluted to achieve a final concentration of 0.72-2.7 mg/ml in an intravenous infusion bag with a minimum volume of 50 ml, containing a solution of 9 mg/ml of sodium chloride solution for injection, 4.5 mg/ml of sodium chloride solution for injection, or 5% glucose solution.

2.Determine the volume of the reconstituted solution at 20 mg/ml required based on the required dose (see below):

3.Extract the appropriate amount of reconstituted solution from the Polivy vial using a sterile syringe and add to the intravenous infusion bag. Discard any unused medicine remaining in the vial.

4.To mix the solution, invert the bag gently. Do not agitate.

5.Inspect the intravenous bag and discard if particles are present.

Reconstituted solution

From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, the storage times in use and the conditions prior to use are the responsibility of the user and, normally, should not exceed 24 hours at refrigerated temperature (2°C-8°C), unless the reconstitution was performed in controlled and validated aseptic conditions. The chemical and physical stability has been demonstrated for up to 72 hours at refrigerated temperature (2°C-8°C) and up to 24 hours at ambient temperature (9°C-25°C).

Diluted solution

From a microbiological point of view, the prepared infusion solution should be used immediately. If not used immediately, the storage time until use and the conditions prior to use will be the responsibility of the user and should not exceed 24 hours at refrigerated temperature (2°C-8°C), unless the dilution was performed under controlled and validated aseptic conditions.The physical and chemical stability has been demonstrated for the times shown in Table 1. The diluted Polivy solution should be discarded if the storage time exceeds the limits specified in Table 1.

Table 1Stability of the prepared infusion solution

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