POLIVY 30 MG POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

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

You should not be given Polivy if:

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

If any of the above apply to you, you should not receive Polivy. If you are not sure, talk to your doctor or nurse before you are given Polivy.

Warnings and precautions

Talk to your doctor or nurse before you are given Polivy if:

• You have ever had brain or nerve problems such as:
• • memory problems
  • difficulty moving or feeling sensations in your body, such as pins and needles, burning, pain and discomfort even with a light touch
  • vision problems
• You have ever had liver problems;
• You think you may have an infection now or have had long-lasting or repeated infections (see “Infections” in section 4).
• If you are to be given a vaccine or know you may need one soon

If you are in any of the above situations (or if you are not sure), talk to your doctor or nurse before you are given Polivy.

Look out for the following side effects

Polivy can cause some serious side effects that you need to tell your doctor or nurse about straight away. These include:

Myelosuppression

Myelosuppression is a disease 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 do blood tests to check your blood cell counts.

Tell your doctor or nurse straight away if:

• You have chills or shakes;
• You have a fever;
• You have headaches;
• You feel tired;
• You feel dizzy;
• You look pale;
• You have unusual bleeding, bruising under the skin, longer bleeding than usual after a blood test or bleeding from the gums.

Peripheral neuropathy

Tell your doctor or nurse straight away if you have any problems with a change in sensation in your skin, especially in your hands or feet, such as:

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

If you have had any of these symptoms before treatment with Polivy, tell your doctor straight away, as well as if you notice any change in them.

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

Infections

The signs and symptoms of infections vary between people; tell your doctor or nurse straight away if you develop symptoms of an infection, such as:

• fever
• cough
• chest pain
• fatigue
• painful skin rash
• sore throat
• burning/pain when urinating
• feeling of weakness or general ill health.

Progressive multifocal leukoencephalopathy (also called PML)

PML is a very rare and potentially life-threatening brain infection, which has been reported in a patient receiving treatment with Polivy together with bendamustine and another medicine called obinutuzumab.

Tell your doctor or nurse straight away if you experience:

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

If you have had any of these symptoms before treatment with Polivy, tell your doctor straight away if you notice any change in them. You may need medical treatment.

Tumour lysis syndrome

Some people may develop unusual levels of 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 “tumour lysis syndrome”. Your doctor, pharmacist or nurse will do blood tests to check your condition.

Infusion-related reactions

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

Hepatotoxicity

This medicine may cause inflammation or damage to liver cells, which can affect their normal 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, resulting in increased values in blood tests.

In most cases, no symptoms are experienced, but tell your doctor and nurse straight away if you experience:

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

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

Children and adolescents

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

Other medicines and Polivy

Other medicines and vaccines

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

Also, tell your doctor or nurse if you are to be vaccinated or if you know you may need to be vaccinated soon.

Contraception (male and female)

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 that you tell your doctor before and during treatment if you are pregnant, think you may be pregnant or are planning to have a baby. This is because Polivy may affect the health of your baby.

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

Breast-feeding

Do not breast-feed while you are receiving Polivy and for at least 3 months after the last dose given, as a small amount of Polivy may pass into breast milk.

Fertility

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

Driving and using machines

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

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, which is essentially “sodium-free”.

Polivy contains polysorbates

Polivy 30 mg contains 1.8 mg of polysorbate 20 in each vial. Polivy 140 mg contains 8.4 mg of polysorbate 20 in each vial, which is equivalent to 1.2 mg/ml. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergy.

3. How Polivy is given

Polivy is given under the supervision of a doctor with experience in the administration of this type of treatment.

It is given into a vein and as an infusion over 90 minutes.

How much Polivy is given

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 is Polivy given

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

What other medicines are given with Polivy

? 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 previous treatment - and when you cannot receive a stem cell transplant.

If you miss a dose of Polivy

If you do not attend your appointment, make another one as soon as possible. For the treatment to be fully effective, it is very important not to miss any dose.

If you stop treatment with Polivy

Do not stop using Polivy unless you have talked to your doctor. This is because stopping treatment could stop the effect of the medicine.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been reported with this medicine:

Serious side effects

Tell your doctor or nurse straight away if you notice any of the following serious side effects, as you may need urgent medical treatment. These can be new symptoms or a change in your current symptoms.

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

• fevers and chills
• rash/hives
• severe infections
• pneumonia (lung infection)
• herpes infection
• viral infections
• upper respiratory tract infection
• skin infection
• lower urinary tract infection
• bleeding or bruising under the skin
• memory loss, difficulty speaking, difficulty walking or vision problems
• yellowing of the skin or the whites of the eyes
• shortness of breath and difficulty breathing

Other side effects:

Tell 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
• diarrhoea or constipation
• pain or inflammation of the mouth and/or the gut (mucositis)
• feeling sick (nausea)
• abdominal pain (belly pain)
• fatigue
• loss of appetite
• weight loss
• infusion-related reactions
• common cold
• hair loss
• change 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 levels of platelets (a type of blood cell that helps blood to clot)

? low levels of red blood cells (anaemia)

? low levels of potassium in the blood (hypokalaemia)

Common: may affect up to 1 in 10 people

• severe infection (sepsis)
• urinary tract infection
• viral infections
• herpes infection
• skin infection
• inflammation of the lungs
• shortness of breath and difficulty breathing
• dizziness
• fluid retention that causes swelling in the lower legs or hands (peripheral oedema)
• high levels of transaminase in the blood
• joint pain
• itching
• chills
• rash
• dry skin
• muscle pain
• change in blood tests:

• decrease in all types of blood cells (pancytopenia)
• low levels of lymphocytes (a type of white blood cell)
• low levels of phosphate in the blood (phosphataemia)
• low levels of calcium in the blood (hypocalcaemia)
• low levels of albumin in the blood (hypoalbuminaemia)

? high levels of lipase enzyme in the blood)

Uncommon: may affect up to 1 in 100 people

• blurred vision

Tell your doctor or nurse straight away if you notice any of the above side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Polivy

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

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

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will dispose of any unused medicine correctly. This will help to protect the environment.

6. Container Content and Additional Information

Polivy Composition

• The active ingredient 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, polysorbate 20. See section 2 "Polivy contains sodium and polysorbates"

Appearance of Polivy and Container Content

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

Each Polivy container 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

To learn more about this medication, contact the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

Other Sources of Information

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

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Information intended only for healthcare professionals:

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

Reconstitution Instructions

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

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

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

? Inspect the reconstituted solution for 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.

Dilution Instructions

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 9 mg/ml sodium chloride solution for injection, 4.5 mg/ml sodium chloride solution for injection, or 5% glucose.
2. Determine the volume of reconstituted solution at 20 mg/ml required based on the necessary dose (see below):

1. Withdraw the appropriate amount of reconstituted solution from the Polivy vial using a sterile syringe and add it to the intravenous infusion bag. Discard any unused medication remaining in the vial.
2. To mix the solution, gently invert the bag. Do not shake.
3. 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 in-use storage times and 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 under controlled and validated aseptic conditions. The chemical and physical stability of the reconstituted solution has been demonstrated for up to 72 hours at refrigerated temperature (2°C-8°C) and up to 24 hours at room 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 before use and the conditions before use are 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. Acceptable physical and chemical stability of the prepared infusion solution has been demonstrated for the times shown in Table 1. The diluted Polivy solution should be discarded if the storage time exceeds the limits indicated in Table 1.

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

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