THERALUGAND

Patient Information Leaflet

Theralugand 40 GBq/mL radiopharmaceutical precursor, solution

lutetium (Lu) chloride
Read this leaflet carefully before this medicinal product is used in combination with Theralugand
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, contact the nuclear medicine physician. See section 4.

Contents of this leaflet

1. What Theralugand is and what it is used for
2. What you need to know before Theralugand is used
3. How the medicinal product labelled with Theralugand is used
4. Possible side effects
5. How to store Theralugand
6. Contents of the pack and other information

1. What Theralugand is and what it is used for

This medicinal product is a type of preparation known as a radiopharmaceutical precursor. It contains the active substance lutetium (Lu) chloride, which emits beta-minus radiation.
Theralugand is not intended to be used alone, but must be combined with other medicinal products (called vectors or carriers) before it can be used. This process, in which a carrier medicinal product is labelled with a radioactive compound, is known as radiolabelling.
Carrier drugs are used in combination with a specific compound—in this case, lutetium (Lu) chloride—to target a specific site. They may consist of substances designed to recognise a particular type of cell in the body. When administered to the patient, the carrier medicinal product labelled with lutetium (Lu) delivers radiation to the site where these cells are located, either to treat a disease or to generate images on a screen used to diagnose or localise a disease.
The use of a medicinal product labelled with Lu involves exposure to radioactivity. The physician and nuclear medicine specialist have determined that the clinical benefit of using a Lu-labelled medicinal product outweighs the risk associated with radiation exposure.
For further information, please consult the package leaflet of the Lu-labelled medicinal product.

2. What you need to know before Theralugand is used

Theralugand must not be used

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

For further information, please consult the package leaflet of the medicine labelled with Lu.
Warnings and precautions
Lutetium (Lu) chloride must not be administered directly to patients. Naturally,
hospital staff should wear standard radiation-protective clothing. All other
individuals in close proximity to the treated patient must be informed about the
possibility of reducing their exposure to radiation emitted by the patient.
Exercise particular caution with medicines labelled with Lu:

• if you have kidney problems or a haematological disease (blood disorders or disorders of the tissues responsible for blood formation, such as bone marrow). In these patients, there is a possibility of increased radiation exposure, which entails a higher risk of certain adverse effects (see section 4. Possible side effects). Your doctor will evaluate the expected benefits of the medicine against the possible risks, and may discontinue treatment if certain adverse effects occur;
• if you have a low number of red blood cells (anaemia);
• if you have a low number of platelets in the blood (thrombocytopenia); platelets are important for stopping bleeding;
• if you have a low 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 lutetium (Lu) chloride is used to label medicinal carriers 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 assess kidney function before and during treatment.
Treatment with medicines labelled with Lu may affect liver function. In this case, you may experience some of the following symptoms: yellowing of the skin and eyes (jaundice), stomach ache (abdominal pain) (particularly in the upper right area of the abdomen), feeling unwell/nausea, vomiting, fatigue, loss of appetite, dark-coloured urine, and increased tendency to bleed or bruise more easily than normal. During treatment, your doctor will perform a blood test to monitor liver function.
Medicinal carriers 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 treating neuroendocrine tumours with medicines labelled with Lu, symptoms associated with hormone release from tumour cells, known as carcinoid crisis, may occur. Inform your doctor if you feel faint or dizzy, or if you experience flushing (sudden redness of the skin, usually of the face or neck) or diarrhoea after treatment.
Treatment with medicines labelled with 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 any occurrence of muscle cramps, muscle weakness, confusion or shortness of breath to your doctor.
Please consult the package leaflet of the medicine labelled with Lu for further warnings and precautions.
Children and adolescents
Consult the nuclear medicine physician if you are under 18 years of age.
The medicine labelled with Lu may be used in children and adolescents under 18 years of age. Please consult the package leaflet of that medicine.
Other medicines and medicines labelled with Theralugand
Inform the 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 receiving medicines labelled with Lu, you must inform the nuclear medicine physician if there is any possibility that you are pregnant, if you have missed a menstrual period, or if you are breastfeeding.
If in doubt, it is important to consult the nuclear medicine specialist responsible for the procedure.
If you are pregnant
Medicines labelled with Lu must not be administered during pregnancy.
If you are breastfeeding
You will be asked to stop breastfeeding during treatment with medicines labelled with Lu. Ask your nuclear medicine physician when you can resume breastfeeding.
Driving and using machines
Effects on the ability to drive and use machines may occur due to the medicine labelled with Lu. Read the package leaflet of that medicine carefully.

3. How to use the medicinal product labelled with Theralugand

There are strict regulations regarding the use, handling and disposal of radiopharmaceuticals. Medicinal products labelled with Lu will only be used in special, controlled areas. This medicinal product will be handled and administered only by trained and qualified personnel experienced in its safe use. Personnel will take particular care to ensure the safe use of the product and will keep you informed about their actions.
The nuclear medicine physician responsible for the procedure will determine the amount of Lu-labelled medicinal product to be used in your case. This will be the minimum quantity necessary to achieve the appropriate result, depending on the specific Lu-labelled medicinal product to be administered and its intended use.
Administration of the Theralugand-labelled medicinal product and conduct of the procedure
Theralugand must only be used in combination with another medicinal product (a vector or carrier) that has been specifically developed and authorized to be combined (labelled) with lutetium (Lu) chloride. The method of administration will depend on the type of vector used. Please read carefully the package leaflet of that medicinal product.
Duration of the procedure
The nuclear medicine specialist will inform you about the usual duration of the procedure.
After administration of the Theralugand-labelled medicinal product
The nuclear medicine physician will inform you of any special precautions to be taken after administration of the Lu-labelled medicinal product. For any questions, please consult your nuclear medicine physician.
If you have been administered more Theralugand-labelled medicinal product than you should have received
Since Lu-labelled medicinal products are 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 needed.
If you have further questions about the use of the Lu-labelled medicinal product, please consult the nuclear medicine physician responsible for the procedure.

4. Possible side effects

Like all medicines, the medicine labelled with Lu may cause side effects, although not
everyone experiences them.
Some side effects can be serious.
If you experience any of the following serious side effects, inform your doctor immediately.
Very common (may affect more than 1 in 10 people):

• Reduced levels of red blood cells (anaemia)
• Reduced levels of white blood cells (leucopenia)
• Reduced levels of lymphocytes, another type of white blood cells (lymphopenia)
• Reduced levels of platelets in the blood (thrombocytopenia)

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

• A type of tumour in which the bone marrow does not produce enough healthy red blood cells or platelets (myelodysplastic syndrome)
• Reduced levels of neutrophils, a type of white blood cells (neutropenia)

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

• A rapidly growing tumour with too many myeloblasts (a type of immature red blood cells) in the bone marrow and blood (acute myeloid leukaemia)

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

• Carcinoid crisis. Carcinoid crisis is a combination of symptoms caused by the release of serotonin and other substances from carcinoid tumours. Symptoms may include facial flushing, spider angiomas (small clusters of dilated blood vessels) on the skin, diarrhoea, difficulty breathing, rapid pulse, and sudden drops in blood pressure causing dizziness and fainting sensations.
• Tumour lysis syndrome. Tumour lysis syndrome is a condition in which tumour cells break down and release their contents into the blood, which can damage organs such as the heart, kidneys, and liver. Symptoms may include nausea, vomiting, weakness, fatigue, muscle cramps, seizures, or changes in urine output.
• Reduced numbers of red blood cells, platelets, and white blood cells (pancytopenia)

Bone marrow tumours (myelodysplastic syndrome and acute myeloid leukaemia) have been reported
many years after treatment with medicines labelled with Lu for neuroendocrine tumours.
Other possible side effects
Very common side effects (may affect more than 1 in 10 people):

• Feeling unwell (nausea)
• Vomiting
• Mild and temporary hair loss (alopecia). Alopecia has been reported in patients receiving peptide receptor radionuclide therapy labelled with lutetium (Lu) for neuroendocrine tumours (tumours originating from cells that release hormones into the blood in response to signals from the nervous system).

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

• Dry mouth (reported among patients with prostate cancer treated with lutetium (Lu), of a temporary nature)

After administration of a medicine labelled with Lu, a certain amount of
ionizing radiation (radioactivity) will be released; this means there is a risk of cancer and of developing
heritable defects. In all cases, the potential benefit of administering the labelled medicine is
greater than the risk from radiation.
For further information, please consult the package leaflet of the medicine labelled with Lu.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your
nuclear medicine specialist. You can also report side effects directly through the national reporting system
listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Theralugand

You do not need to store this medicine. This medicine 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 exclusively for the specialist:
Keep this medicine out of the sight and reach of children.
Theralugand must not be used after the expiry date and time stated on the label after "Exp." Theralugand will be stored in its original packaging, which provides protection from radiation.
This medicine does not require any specific storage temperature.

6. Package contents and other information

What Theralugand contains

• The active substance is lutetium (Lu) chloride. One mL of sterile solution contains 40 GBq of lutetium (Lu) chloride at the reference date and time (Activity Reference Time, ART), corresponding to a maximum of 10 micrograms of lutetium (Lu) (as chloride). (GBq: the gigabecquerel is the unit used to measure radioactivity).
• The other component is diluted hydrochloric acid.

Description of the appearance of Theralugand and contents of the pack
Theralugand is a radiopharmaceutical precursor. It is a clear, colourless solution in a 3 mL or 10 mL colourless glass type I vial, with a conical bottom and flat base, closed with a bromobutyl rubber stopper and an aluminium crimp cap.
Each pack contains one vial placed inside a lead container with an acrylic coating for protective shielding, packaged in a metal can and an outer cardboard box.
The volume in a vial ranges from 0.1 to 5 mL of solution (corresponding to an activity between 4 and 200 GBq at ART). The volume depends on the amount of medicinal product to be combined with Theralugand required for administration by the nuclear medicine physician.

Marketing Authorisation Holder
Eckert & Ziegler Radiopharma GmbH
Robert-Rössle-Str. 10
13125 Berlin
Germany

Manufacturer
Eckert & Ziegler Radiopharma GmbH
Gieselweg 1
38110 Braunschweig
Germany

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

The following information is intended for healthcare professionals only:

The complete product characteristics summary of Theralugand is provided as a separate document
in the medicinal product's 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.