Polivy - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Polivy 30 mg powder for concentrate for solution for infusion

Polivy 140 mg powder for concentrate for solution for infusion polatuzumab vedotin

This medicine is subject to additional monitoring. This will allow quick identification of new safetyinformation. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given 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 or nurse.
• If you get any side effects, talk to your doctor or nurse.This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Polivy is and what it is used for

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

• 3. How Polivy is given

• 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 that contains the active substance polatuzumab vedotin.

What Polivy is used for

Polivy is given to treat “diffuse large B-cell lymphoma” that has come back or has not got better with at least one previous therapy and when you cannot receive a stem cell transplant.

Diffuse large B-cell lymphoma is a cancer that develops from B lymphocytes also called B-cells. These are a type of blood cells.

How Polivy works

The active substance in Polivy is made up of a monoclonal antibody linked to MMAE, a substance that can kill cancer cells. The monoclonal antibody part of the medicine attaches to a target on B cells. Once attached to B cells, the medicine releases MMAE into the B cells and kills them.

What other medicines Polivy is given with

Polivy is given in combination with two other cancer medicines called rituximab and bendamustine.

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

You must not be given Polivy

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

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 any of the following apply to you (or you are not sure):

• you have ever had brain or nerve problems such as:

• – memory problems

• – difficulty moving or sensations in your body such as feeling pins and needles, burning, pain and discomfort even from slight touch

• – eyesight problems

• you have ever had liver problems
• you think you have an infection or have had long-lasting or repeated infections such as herpes (see “Infections” in section 4)
• you are due to have a vaccine or you know you may need to have one in the near future

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

Pay attention to 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 condition in which the production of blood cells is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Your doctor will do blood tests to check your blood cell count.

Tell your doctor or nurse straight away if you:

• develop chills or shivering
• have a fever
• have headaches
• feel tired
• feel dizzy
• look pale
• have unusual bleeding, bruising under the skin, bleeding longer than usual after your blood has been drawn, or bleeding from your gums.

Peripheral neuropathy

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

• numbness
• tingling
• a burning sensation
• pain
• discomfort or weakness.

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

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

Infections

Signs and symptoms of infections vary between individuals, tell your doctor or nurse straight away if you develop symptoms of an infection such as:

• fever
• cough
• chest pain
• tiredness
• painful rash
• sore throat
• burning pain when passing urine
• feeling weak or generally unwell.

Progressive multifocal leukoencephalopathy (PML)

PML is a very rare and life threatening infection in the brain, that has occured in one patient treated with Polivy together with bendamustine and another medicine called obinutuzumab.

Tell your doctor or nurse straight away if you have:

• memory loss
• trouble speaking
• difficulty walking
• problems with your eyesight.

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

Tumour lysis syndrome

Some people may develop unusual levels of some substances (such as potassium and uric acid) in the blood caused by the fast breakdown of cancer cells during treatment. This is called tumour lysis syndrome. Your doctor, pharmacist or nurse will do blood tests to check for the condition.

Infusion-related reactions

Infusion-related reactions, allergic or anaphylactic (more severe allergic) reactions can happen. Your doctor or nurse will check for side effects during your infusion and for 30 to 90 minutes afterwards. If you get any serious reaction, your doctor may stop treatment with Polivy.

Liver damage

This medicine can cause inflammation or damage to cells in the liver that affect the normal function of the liver. Injured liver cells may leak high amounts of certain substances (liver enzymes and bilirubin) into the bloodstream, in which can be detected by blood tests.

In most cases you will not have any symptoms but tell your doctor or nurse straight away if you get:

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

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

Children and adolescents

This medicine should not be used in children or young people under the age of 18. This is because there is no information about its use in this age group.

Other medicines and Polivy

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

Contraception (women and men)

If you are a woman of childbearing age, you must use effective contraception during treatment and for 9 months after the last dose of Polivy.

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

Pregnancy

It is important to tell your doctor before and during treatment if you are pregnant, think you may be pregnant, or are planning to get pregnant. This is because Polivy can affect your baby’s health. You should not use this medicine if you are pregnant unless you and your doctor decide that the benefit to you outweighs possible risk to the unborn baby.

Breast-feeding

Do not breast-feed while receiving Polivy and for at least 3 months after the last dose, because small amount of Polivy may pass into your breast milk.

Fertility

Men being treated with this medicine are advised to have sperm samples preserved and stored before treatment.

Driving and using machines

Polivy has a minor influence on your ability to drive, cycle or use any tools or machines. If you get infusion-related reactions or nerve damage, or if you feel tired, weak or dizzy (see section 4) do not drive, cycle or use tools or machines until the reaction stops.

See section 4 for more information about side effects.

Polivy contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

• 3. How Polivy is given

Polivy is given under the supervision of a doctor experienced in giving such treatments. It is given into a vein, as a drip over 90 minutes.

How much Polivy is given

The dose of this medicine depends on your body weight.

• The usual starting dose is 1.8 mg for each kilogram of your body weight.

If you have peripheral neuropathy, your doctor may lower your dose to 1.4 mg for each kilogram of your body weight.

You will be given 6 treatment cycles of Polivy in combination with two other medicines called rituximab and bendamustine.

Each cycle lasts 21 days.

If you miss a dose of Polivy

If you miss an appointment, make another one straight away. For the treatment to be fully effective, it is very important not to miss a dose.

If you stop receiving Polivy

Do not stop treatment with Polivy unless you have discussed this with your doctor. This is because stopping treatment may make your condition worse.

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 – you may need urgent medical treatment. These may be new symptoms or a change in your current symptoms.

• fevers and chills
• rash/hives
• severe infections
• pneumonia (lung infection)
• herpes infection
• viral infections
• unusual bleeding or bruising under the skin
• memory loss, trouble speaking, difficulty walking or problems with your eyesight
• yellowing of skin or whites of your eyes

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)

• severe infections
• fever
• cough
• vomiting
• pneumonia (lung infection)
• diarrhoea or constipation
• feeling sick (nausea)
• abdominal (belly) pain
• feeling tired (anaemia)
• not feeling hungry
• loss of weight
• infusion-related reactions
• common cold
• dizziness
• unusual sensations

Common (may affect up to 1 in 10 people)

• chills
• viral infections
• herpes infection
• problems walking
• inflammation of the lungs
• raised liver enzymes
• joint pain
• itchiness

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet you can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Polivy

Polivy will be stored by the healthcare professionals at 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 and the vial after EXP. The expiry date refers to the last day of that month.
• Store in a refrigerator (2°C – 8°C).
• Do not freeze.
• Keep the container in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Polivy contains

• The active substance is polatuzumab vedotin.
• Polivy 30 mg: Each vial contains 30 milligrams (mg) polatuzumab vedotin.
• Polivy 140 mg: Each vial contains 140 milligrams (mg) polatuzumab vedotin.
• After reconstitution each millilitre (mL) contains 20 mg polatuzumab vedotin.
• The other ingredients are: succinic acid, sodium hydroxide, sucrose, polysorbate 20. See section “Polivy contains sodium”.

What Polivy looks like and contents of the pack

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

Each pack of Polivy consists of one vial.

Marketing Authorisation 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 any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien N.V. Roche S.A. Tél/Tel: +32 (0) 2 525 82 11	Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799
Etnrapufl Pom Etnrapua EOOfl	Luxembourg/Lu­xemburg (Voir/siehe Belgique/Belgien)

Ten: +359 2 818 44 44

Ceská republika Roche s. r. O. Tel: +420 – 2 20382111	Magyarország Roche (Magyarország) Kft. Tel: +36 – 23 446 800
Danmark Roche a/s	Malta Irreferi ghall-Irlanda

Tlf: +45 – 36 39 99 99

Deutschland Roche Pharma AG Tel: +49 (0) 7624 140	Nederland Roche Nederland B.V. Tel: +31 (0) 348 438050
Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380	Norge Roche Norge AS Tlf: +47 – 22 78 90 00
EMáSa Roche (Hellas) A.E. Tql: +30 210 61 66 100	Österreich Roche Austria GmbH Tel: +43 (0) 1 27739
España Roche Farma S.A. Tel: +34 – 91 324 81 00	Polska Roche Polska Sp.z o.o. Tel: +48 – 22 345 18 88

Portugal

Roche Farmacéutica Química, Lda

Tel: +351 – 21 425 70 00

Romanía

Roche Romanía S.R.L.

Tel: +40 21 206 47 01

Slovenija

Roche farmacevtska družba d.o.o.

Tel: +386 – 1 360 26 00

Slovenská republika Roche Slovensko, s.r.o. Tel: +421 – 2 52638201

Suomi/Finland

Roche Oy

Puh/Tel: +358 (0) 10 554 500

Sverige

Roche AB

Tel: +46 (0) 8 726 1200

United Kingdom (Northern Ireland)

Roche Products (Ireland) Ltd.

Tel: +44 (0) 1707 366000

This leaflet was last revised in {MM/YYYY }

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only:

Procedures for proper handling and disposal of anticancer medicinal products should be considered.

Instructions for reconstitution

• Polivy 30 mg: Using a sterile syringe, slowly inject 1.8 mL of sterile water for injection into the

30 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin. Direct the stream toward the wall of the vial and not directly on the lyophilized cake.

• Polivy 140 mg: Using a sterile syringe, slowly inject 7.2 mL of sterile water for injection into the 140 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin. Direct the stream toward the wall of the vial and not directly on the lyophilized cake.
• Swirl the vial gently until completely dissolved. Do not shake.
• Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear colourless to slightly brown, clear to slightly opalescent, and free of visible particulates. Do not use if the reconstituted solution is discoloured, is cloudy, or contains visible particulates.

Instructions for dilution

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 9 mg/mL sodium chloride solution for

injection, or 4.5 mg/mL sodium chloride solution for injection, or 5% glucose.

Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose

Polivy dose (mg/kg) X patient’s weight (kg) Reconstituted vial concentration (20 mg/mL)

Withdraw the required volume of reconstituted solution from the Polivy vial using a sterile syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial. Gently mix the intravenous bag by slowly inverting the bag. Do not shake.

Inspect the intravenous bag for particulates and discard if present.

Reconstituted solution

From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours refrigerated (2 °C – 8 °C), unless reconstitution has taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of the reconstituted solution has been demonstrated for up to 72 hours refrigerated (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 solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours refrigerated (2 °C – 8 °C), unless dilution has taken place in controlled and validated aseptic conditions. Chemical and physical stability of the prepared solution for infusion has been demonstrated for the durations listed in Table 1. Discard diluted Polivy solution if storage time exceeds the limits specified in Table 1.

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

Diluent used to prepare solution for infusion	Solution for infusion storage conditions1
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 – 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 – 25 °C)

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

40

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

6.4 Special precautions for storage

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Polivy 30 mg powder for concentrate for solution for infusion:

mL vial (colourless Type 1 glass) closed with a stopper (fluororesin laminate), with an aluminium seal with plastic flip-off cap containing 30 mg polatuzumab vedotin. Pack size of one vial.