Lutetium (177lu) Vipivotide Tetraxetan: package leaflet

What Pluvicto is
Pluvicto contains lutetium (177Lu) vipivotide tetraxetan. This medicine is a radiopharmaceutical product for therapy only.

What Pluvicto is used for
Pluvicto is used to treat adults with progressive castration-resistant prostate cancer that has spread to other parts of the body (metastatic) and has already been treated with other cancer treatments.
Castration-resistant prostate cancer is a cancer of the prostate (a gland of the male reproductive system) that does not respond to treatment that reduces male hormones. Pluvicto is used if the prostate cancer cells have a protein on their surface called prostate-specific membrane antigen (PSMA).

How Pluvicto works
Pluvicto binds to PSMA found on the surface of the prostate cancer cells. Once bound, the radioactive substance in Pluvicto, lutetium-177, gives off radiation that causes the prostate cancer cells to die.

Your doctor will carry out tests to see if PSMA is present on the surface of the cancer cells. Your cancer is more likely to respond to treatment with Pluvicto if the test result is positive.

The use of Pluvicto involves exposure to amounts of radioactivity. Your doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain from the procedure with the radiopharmaceutical outweighs the risk due to radiation.

If you have any questions about how Pluvicto works or why this medicine has been prescribed for you, ask your nuclear medicine doctor.

Follow all instructions given by your nuclear medicine doctor carefully. They may differ from the general information contained in this leaflet.

Pluvicto must not be used
- if you are allergic to lutetium (177Lu) vipivotide tetraxetan or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
If any of these apply to you, tell your nuclear medicine doctor before receiving Pluvicto:
- if you have low levels of certain types of cells in the blood (red blood cells, white blood cells, neutrophils, platelets)
- if you have or have had tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal or bleeding for longer than normal, or frequent infections with signs such as fever, chills, sore throat or mouth ulcers (possible signs of myelosuppression [a condition in which the bone marrow cannot make enough blood cells])
- if you have or have had kidney problems
- if you have or have had any other type of cancer or treatment for cancer, as Pluvicto contributes to your overall long-term cumulative radiation exposure

Before administration of Pluvicto you should:
- drink plenty of water so that you remain hydrated and urinate as often as possible during the first hours after administration

Children and adolescents
The safety and efficacy of this medicine have not been established in children and adolescents under 18 years of age. This medicine should not be given to children or adolescents aged under 18 years because no data are available in this age group.

Pregnancy, breast-feeding and fertility
Pluvicto is not intended for use in women.

Before you receive Pluvicto, tell your nuclear medicine doctor if you are sexually active as all radioactive emissions, including those from Pluvicto, can cause harm to an unborn baby.

Fertility
Pluvicto may cause infertility. Please ask your nuclear medicine doctor how this may affect you, especially if you are planning to have children in the future. You may wish to seek advice on preservation of sperm before treatment starts.

Contraception in males
- You should avoid sexual activity for 7 days after administration of Pluvicto.
- You should not father a child and should use a condom during intercourse throughout treatment with Pluvicto and for 14 weeks after your last dose.
- Tell your nuclear medicine doctor immediately if you father a child at any time during this time period.

Driving and using machines
It is considered unlikely that Pluvicto will affect your ability to drive or use machines.

Pluvicto contains sodium
This medicine contains up to 88.75 mg sodium (main component of cooking/table salt) in each vial.
This is equivalent to 4.4% of the recommended maximum daily dietary intake of sodium for an adult.

There are strict laws on the use, handling and disposal of radiopharmaceutical products. Pluvicto will only be used in special controlled areas. This radiopharmaceutical product will only be handled and given to you by people who are trained and qualified to use it safely. These persons will take special care for the safe use of this radiopharmaceutical product and will keep you informed of their actions.

How much Pluvicto is given
The recommended treatment regimen of Pluvicto is 7 400 MBq (megabecquerel, the unit used to express radioactivity), which is given approximately every 6 weeks for up to a total of 6 doses.

Administration of Pluvicto and conduct of the procedure
Pluvicto is administered directly into a vein.

Duration of the procedure
Your nuclear medicine doctor will inform you about the usual duration of the procedure.

If you have questions about how long you will receive Pluvicto, talk to your nuclear medicine doctor.

Treatment monitoring
Your nuclear medicine doctor will do blood tests before and during treatment to check your condition and to detect any side effects as early as possible. Based on the results, your nuclear medicine doctor may decide to delay, change or stop your treatment with Pluvicto if necessary.

After administration of Pluvicto, you should:
- drink plenty of water for 2 days so that you remain hydrated and urinate as often as possible to eliminate the radiopharmaceutical product from your body

Because this medicine is radioactive, you will have to follow the instructions described below to minimise radiation exposure to others unless otherwise instructed by your nuclear medicine doctor.

Contact with others, children, and/or pregnant women
- Limit close contact (less than 1 metre) with:
- others for 2 days
- children and pregnant women for 7 days
- Sleep in a separate room from:
- others for 3 days
- children for 7 days
- pregnant women for 15 days
- Avoid sexual activity for 7 days
- Do not father a child and do use a condom during intercourse throughout treatment with Pluvicto and for 14 weeks after your last dose

Use of toilets
Take special precautions to avoid contamination for 2 days after administration:
- You must always sit when using the toilet.
- It is essential that you use toilet paper every time you use the toilet.
- Always wash your hands well after using the toilet.
- Flush all wipes and/or toilet paper down the toilet immediately after use.
- Flush any tissues or any other items that contain bodily waste, such as blood, urine and faeces down the toilet. Items that cannot be flushed down the toilet, such as bandages, must be placed in separate plastic waste disposal bags (according to “Waste disposal recommendations” below).
- Any special medical equipment that could be contaminated by your bodily fluids (e.g. catheter bags, colostomy bags, bedpans, water nozzles) must be emptied immediately into the toilet and then cleaned.

Showering and laundry
- Take a shower every day for at least 7 days after administration.
- Wash your underwear, pyjamas, sheets and any clothes that contain sweat, blood or urine separately from the laundry of others in your household, using a standard washing cycle. You do not need to use bleach and you do not need extra rinses.

Care givers
For 2-3 days after administration:
- People who are confined to bed or have reduced mobility will preferably receive assistance from a care giver. It is recommended that when providing assistance in the bathroom, the care giver wears disposable gloves.
- Care givers who clean up vomit, blood, urine or faeces should wear plastic gloves, which should be disposed of in a separate plastic waste disposal bag (see “Waste disposal recommendations” below).

Waste disposal recommendations
- All items to be thrown away should be discarded in a separate plastic waste disposal bag to be used only for this purpose.
- Keep the plastic waste disposal bags separate from the other household waste and away from children and animals.
- A member of the hospital staff will tell you how and when to get rid of these waste disposal bags.

Hospitalisation and emergency care
- If for any reason you require emergency medical assistance or are unexpectedly admitted to the hospital during the first 7 days after administration, you should inform the healthcare professionals about the name, date and dose of your radioactive treatment.

Other precautions
- The nuclear medicine doctor will inform you if you need to take any other special precautions after receiving this medicine. Contact your nuclear medicine doctor if you have any questions.

If you have been given more Pluvicto than you should
An overdose is unlikely because you will only receive Pluvicto in doses that are precisely controlled by the nuclear medicine doctor supervising the procedure. However, in the event of an overdose, you will receive the appropriate treatment.

If you forget to receive Pluvicto
If you miss an appointment to receive Pluvicto, contact your nuclear medicine doctor as soon as possible to reschedule.

Should you have any further questions on the use of Pluvicto, please ask the nuclear medicine doctor who supervises the procedure.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some side effects could be serious
If you experience any of the following serious side effects, tell your nuclear medicine doctor right away.

Very common: may affect more than 1 in 10 people
- tiredness, weakness, pale skin or shortness of breath (possible signs of low levels of red blood cells [anaemia])
- bleeding or bruising more easily than normal or bleeding for longer than normal (possible signs of low levels of platelets [thrombocytopenia])
- frequent infections with signs such as fever, sore throat or mouth ulcers (possible signs of low levels of white blood cells [leukopenia, lymphopenia])

Common: may affect up to 1 in every 10 people
- passing urine less often or in much smaller amounts than usual (possible sign of kidney problems [acute kidney injury])
- tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal or bleeding for longer than normal or frequent infections with signs such as fever, chills, sore throat or mouth ulcers (possible signs of low levels of blood cells [pancytopenia])

Uncommon: may affect up to 1 in every 100 people
- Weakness, pale skin, bleeding or bruising more easily than normal or difficulty to stop bleeding and frequent infections with signs such as fever, chills, sore throat or mouth ulcers (bone marrow failure)

Other possible side effects
Other side effects include the following listed below. If these side effects become severe, please tell your nuclear medicine doctor.

Very common: may affect more than 1 in 10 people
- tiredness (fatigue)
- dry mouth
- nausea
- loss of appetite
- changes in bowel movements (constipation or diarrhoea)
- vomiting
- frequent urination with pain or burning sensation (urinary tract infection)
- abdominal pain
- weight loss
- swollen hands, ankles or feet (peripheral oedema)

Common: may affect up to 1 in every 10 people
- dizziness
- headache
- disturbed sense of taste (dysgeusia)
- fever (pyrexia)
- trouble swallowing and/or heartburn (oesophageal disorder)
- dry eyes
- oral fungal infection
- dizziness, with a spinning sensation (vertigo)
- mouth sores (stomatitis)
- dry skin

Reporting of side effects
If you get any side effects, talk to your nuclear medicine doctor. 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 Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

You will not have to store this medicine. This medicine is stored under the responsibility of the specialist in appropriate premises. Storage of radiopharmaceuticals will be in accordance with national regulations on radioactive materials.

The following information is intended for the specialist only:
- Keep this medicine out of the sight and reach of children.
- Do not freeze.
- Store in the original package in order to protect from ionising radiation (lead shielding).
- Pluvicto must not be used after the expiry date and time which are stated on the lead shielding container and vial labels after EXP.
- Any unused medicine or waste material should be disposed of in accordance with local requirements.

What Pluvicto contains
- The active substance is lutetium (177Lu) vipivotide tetraxetan. One mL of solution contains 1 000 MBq lutetium (177Lu) vipivotide tetraxetan at the date and time of calibration.
- The other ingredients are: acetic acid, sodium acetate, gentisic acid, sodium ascorbate, pentetic acid, water for injections (see “Pluvicto contains sodium” in section 2).

What Pluvicto looks like and contents of the pack
Pluvicto is a clear, colourless to slightly yellow solution supplied in a clear, colourless type I glass vial, closed with a bromobutyl rubber stopper and aluminium seal.
Each vial contains a volume of solution that can range from 7.5 mL to 12.5 mL corresponding to a radioactivity of 7 400 MBq ±10% at the date and time of administration.
The vial is enclosed within a lead container for protective shielding.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Advanced Accelerator Applications (Italy) S.R.L.
Via Ribes 5
10010
Colleretto Giacosa (TO)
Italy

Advanced Accelerator Applications Ibérica, S.L.U.
Polígono Industrial la Cuesta – Sector 3
Parcelas 1 y 2 La Almunia de Doña Godina
50100 Zaragoza
Spain

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

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11
Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Sverige AB
Tlf.: +46 8 732 32 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 111
Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
ΒΙΟΚΟΣΜΟΣ ΑΕΒΕ
Τηλ: +30 22920 63900 ή
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570
España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Novartis Sverige AB
Sími: +46 8 732 32 00

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Sverige AB
Puh/Tel: +46 8 732 32 00

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu

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The following information is intended for healthcare professionals only:

The complete SmPC of Pluvicto is provided as a separate document in the product package, with the objective to provide healthcare professionals with other additional scientific and practical information about the administration and use of this radiopharmaceutical.

Please refer to the SmPC.