Lutetium (177LU) chloride Billev

Patient Information Leaflet

Lutetium (Lu) chloride Billev 51.8 GBq/mL radiopharmaceutical precursor, solution

lutetium (Lu) chloride
Please read this leaflet carefully before using the medicinal product combined with
Lutetium (Lu) chloride Billev, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask the nuclear medicine physician in charge of the procedure.
• If you experience any side effects, including those not listed in this leaflet, inform your nuclear medicine physician. See section 4.

Contents of this leaflet

1. What Lutetium (Lu) chloride Billev is and what it is used for
2. What you need to know before using Lutetium (Lu) chloride Billev
3. How to use the medicinal product labelled with Lutetium (Lu) chloride Billev
4. Possible side effects
5. How to store Lutetium (Lu) chloride Billev
6. Package contents and other information

1. What Lutezio (Lu) chlorure Billev is and what it is used for

Lutezio (Lu) chlorure Billev is a type of product called a radiopharmaceutical precursor. It contains the active substance lutetium (Lu) chloride, which emits beta-minus radiation.
Lutezio (Lu) chlorure Billev is not intended to be used alone. Before administration, it must be combined with other medicines, known as vector medicines, specifically developed for use with lutetium (Lu) chloride. This process is called radiolabelling.
These vector medicines may be substances designed to recognize a specific type of cell in the body. The vector medicine is administered to the patient according to the instructions provided in the product information of that medicine. It then delivers the radiation to the required site within the body, either to treat the disease or to generate images on a screen used to diagnose the disease.
Using a medicine labelled with Lutezio (Lu) chlorure Billev involves exposure to radioactivity. Your doctor and nuclear medicine specialist have determined that the clinical benefit obtained from using Lutezio (Lu) chlorure Billev outweighs the risk associated with radiation exposure.
For further information, please consult the package leaflet of the medicine to be labelled with

Lutetium (Lu) chloride Billev.

2. What you need to know before using Lutetium (Lu) chloride Billev

Lutetium (Lu) chloride Billev must not be used

• if you are allergic to lutetium (Lu) chloride or to any of the other components of this medicinal product (listed in section 6);
• if you are pregnant or think you might be pregnant.

For further information, please consult the package leaflet of the medicinal product to be labelled with

Lutetium (Lu) Chloride Billev

Warnings and precautions
Lutetium (Lu) chloride Billev must not be administered directly to patients.
Exercise particular caution with the medicinal product labelled with Lutetium (Lu) chloride Billev:

• if you have kidney problems or bone marrow disease.

Treatment with lutetium (Lu) may cause the following undesirable effects:

• reduced number of red blood cells (anaemia);
• reduced number of blood platelets (thrombocytopenia); platelets are important for stopping bleeding;
• reduced number of white blood cells (leucopenia, lymphopenia or neutropenia); white blood cells are important for protecting the body against infections.

These events are mostly mild and temporary. In some patients, a reduced number of all three types of blood cells (red blood cells, platelets and white blood cells – pancytopenia) has been reported.
In patients with pancytopenia, treatment must be discontinued.
Since lutetium (Lu) may, in some cases, affect blood cells, your doctor will perform blood tests before starting treatment and at regular intervals during treatment. Contact your doctor if you experience shortness of breath, bruising, nosebleeds, bleeding gums or develop fever.
When this medicinal product is used to label carrier medicines known as somatostatin analogues, used to treat tumours called neuroendocrine tumours, the labelled carrier medicine is excreted by the kidneys. Therefore, your doctor will take a blood sample to measure your kidney function before and during treatment.
Treatment with lutetium (Lu) may affect liver function. During treatment, your doctor will perform a blood test to monitor your liver function.
Medicinal products labelled with lutetium (Lu) may be administered directly into a vein through a device (tube) known as a cannula. Cases of fluid leakage into surrounding tissue (extravasation) have been reported. Inform your doctor if you experience swelling or pain in your arm.
After treatment of neuroendocrine tumours with lutetium (Lu), you may develop symptoms related to the release of hormones from tumour cells, known as carcinoid crisis. Inform your doctor if you feel faint, dizzy, or develop flushing or diarrhoea after treatment.
Treatment with lutetium (Lu) may cause tumour lysis syndrome, a condition caused by the rapid breakdown of tumour cells. This may lead, within one week of treatment, to abnormal blood test results, irregular heartbeat, kidney failure or seizures. Your doctor will perform blood tests to monitor you. Report to your doctor if you experience muscle cramps, muscle weakness, confusion or shortness of breath.
Please consult the package leaflet of the medicinal product to be labelled with Lutetium (Lu) chloride Billev for further warnings and precautions.

Children and adolescents
If you are under 18 years of age, consult your nuclear medicine physician.
The use of Lutetium (Lu) chloride Billev in children and adolescents under 18 years of age depends on the medicinal product to be labelled with Lutetium (Lu) chloride Billev. Refer to the package leaflet of that medicinal product.

Other medicines and medicinal products labelled with Lutetium (Lu) chloride Billev
Inform your nuclear medicine physician if you are taking, have recently taken or might take any other medicines, as they could interfere with the procedure.
It is not known whether lutetium (Lu) chloride may interact with other medicines, as specific studies have not been conducted.

Pregnancy and breastfeeding
Before administration of medicinal products labelled with Lutetium (Lu) chloride Billev, you must inform your nuclear medicine physician if there is any possibility you are pregnant, if you have missed a menstrual period or if you are breastfeeding with breast milk.
In case of doubt, it is important to consult the nuclear medicine specialist responsible for the procedure.

If you are pregnant
Medicinal products labelled with Lutetium (Lu) chloride Billev must not be administered during pregnancy.

If you are breastfeeding
You will be asked to discontinue breastfeeding.
Ask your nuclear medicine physician when you may resume breastfeeding.

Driving and using machines
Your ability to drive and use machines may be affected by the medicinal product used in combination with Lutetium (Lu) chloride Billev. Read the package leaflet of that medicinal product carefully.

3. How to use the medicinal product labelled with Lutetium (Lu) Chloride Billev

There are strict regulations regarding the use, handling, and disposal of radiopharmaceuticals. Medicinal products labelled with Lutetium (Lu) Chloride Billev will be used only in designated and controlled areas. This medicine will be handled and administered to you only by trained and qualified personnel experienced in its safe use. The staff will take special precautions to ensure the safe use of the medicine and will keep you informed about the actions taken.

The nuclear medicine physician responsible for the procedure will determine the amount of the medicinal product labelled with Lutetium (Lu) Chloride Billev to be used in your case. This will be the minimum quantity necessary to achieve the appropriate result, depending on the medicinal product administered with Lutetium (Lu) Chloride Billev and its intended use.

Administration of the medicinal product labelled with Lutetium (Lu) Chloride Billev and procedure conduct
Lutetium (Lu) Chloride Billev must only be used in combination with another medicinal product (a vector or carrier) that has been specifically developed and authorized for combination with Lutetium (Lu) Chloride. The administration will depend on the type of vector medicinal product. Please read the package leaflet of that medicinal product carefully.

Duration of the procedure
The nuclear medicine specialist will inform you about the expected duration of the procedure.

After administration of the medicinal product labelled with Lutetium (Lu) Chloride Billev
The nuclear medicine physician will inform you of any special precautions to be taken after administration of the medicinal product labelled with Lutetium (Lu) Chloride Billev. For any questions, please consult your nuclear medicine physician.

If you have been given more medicinal product labelled with Lutetium (Lu) Chloride Billev than you should have
Since the medicinal product labelled with Lutetium (Lu) Chloride Billev is handled by a nuclear medicine physician under strictly controlled conditions, the risk of overdose is very limited. However, in the event of an overdose, you will receive appropriate treatment as required.

If you have any further questions about the use of the medicinal product labelled with Lutetium (Lu) Chloride Billev, please consult the nuclear medicine physician responsible for the procedure.

4. Possible side effects

Like all medicines, the medicine labelled with Lutetium (Lu) chloride Billev can cause side effects,
although not all people experience them.
'Dry mouth', of a temporary nature, has been reported in patients with prostate carcinoma who
were being treated with lutetium (Lu).
Very common side effects (may affect more than 1 in 10 people):

• Decrease in the number of blood cells (platelets, red blood cells or white blood cells)
• Nausea
• Vomiting

Side effects reported in patients treated for neuroendocrine tumours:
Very common (may affect more than 1 in 10 people):

• Mild and temporary hair loss

Common (may affect up to 1 in 10 people):

• Bone marrow tumour (myelodysplastic syndrome)
• Low number of white blood cells (neutropenia)

Uncommon (may affect up to 1 in 100 people):

• Bone marrow tumour (acute myeloid leukaemia)

Not known (frequency cannot be estimated from the available data):

• Carcinoid crisis (release of hormones from tumour cells)
• Tumour lysis syndrome (rapid breakdown of tumour cells)
• Reduced number of red blood cells, platelets and white blood cells (pancytopenia)
• Dry mouth

Bone marrow tumours (myelodysplastic syndrome and acute myeloid leukaemia) have been reported
many years after treatment with lutetium (Lu)-labelled vector medicines for neuroendocrine tumours.
After administration of the medicine labelled with Lutetium (Lu) chloride Billev, a certain amount of
ionizing radiation (radioactivity) will be released. This means there is a certain risk of cancer and
development of hereditary defects. In all cases, the potential benefit of administering the
labelled medicine outweighs the risk from radiation.
For further information, please consult the package leaflet of the medicine to be labelled with

Lutetium (Lu) chloride Billev.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, consult the nuclear medicine specialist. You can also report adverse reactions directly through the national reporting system listed in Annex V. By reporting adverse reactions, you can help provide more information on the safety of this medicinal product.

5. How to store Lutezio (Lu) chloride Billev

You must not store this medicinal product. This medicinal product is stored under the responsibility of a specialist in suitable premises. Storage of radiopharmaceuticals must comply with national regulations concerning radioactive materials.

The following information is intended for specialists only:
Keep this medicinal product out of the sight and reach of children.
Lutezio (Lu) chloride Billev must not be used after the expiry date and time stated on the label after the word "Exp.". Lutezio (Lu) chloride Billev will be stored in its original packaging, which provides protection from radiation.
This medicinal product requires no special temperature conditions for storage.

6. Package contents and other information

What Lutetium (Lu) Chloride Billev contains

• The active substance is lutetium (Lu) chloride. 1 mL of sterile solution contains 51.8 GBq of lutetium (Lu) chloride at the reference date and time (ART, activity reference time) (corresponding to a maximum of 12.6 micrograms of lutetium (Lu) (as chloride). (GBq: the gigabecquerel is the unit used to measure radioactivity).
• The other component is hydrochloric acid, diluted.

Description of the appearance of Lutetium (Lu) Chloride Billev and contents of the pack
Lutetium (Lu) Chloride Billev is a radiopharmaceutical precursor. It is a clear, colourless solution in a 5 mL or 10 mL transparent type I glass vial with either a conical or flat base, closed with a bromobutyl rubber stopper coated in Teflon, and sealed with an aluminium cap.
The vials are placed in a lead container for protective shielding and are packaged in a polystyrene box and an outer cardboard box.
Pack sizes:
5 mL vial: 1, 2 or 3 vials
10 mL vial: 1, 2 or 3 vials
Not all pack sizes may be marketed.
The volume in a vial ranges from 0.1 to 8 mL of solution (corresponding to an activity between 5.2 and 414.4 GBq at the reference date and time). The volume depends on the amount of medicinal product to be combined with Lutetium (Lu) Chloride Billev required for administration by the nuclear medicine physician.

Marketing Authorisation Holder
Billev Pharma ApS
Slotsmarken 10
2970 Hørsholm
Denmark

Manufacturer
Cilatus Manufacturing Services Limited
Pembroke House
28-32 Pembroke Street Upper
Dublin 2
D02 EK84
Ireland
Seibersdorf Labor GmbH
Forschungszentrum
2444 Seibersdorf
Austria

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

The complete product characteristics summary of Lutezio (Lu) chloride Billev is provided as a
separate document within the medicinal product packaging, in order to provide healthcare professionals
with additional scientific and practical information on the administration and use of this radiopharmaceutical.
Please consult the product characteristics summary.