Xofigo 1100 kBq/ml injectable solution

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

Xofigo must not be given

• In combination with abiraterone and prednisone/prednisolone (which are used together to treat prostate cancer).

Warnings and precautions

Talk to your doctor before you are given Xofigo

• Xofigo must not be given in combination with abiraterone and prednisone/prednisolone due to a possible increased risk of bone fractures and deaths. Additionally, there are concerns about the effects of Xofigo when given with other medicines used to treat prostate cancer that has spread. Tell your doctor if you are already taking any of these medicines.

• If you are going to receive Xofigo after treatment with abiraterone and prednisone/prednisolone, you must wait at least 5 days before starting treatment with Xofigo.
• If you are going to receive another cancer treatment after Xofigo, you must wait at least 30 days before starting the other treatment.
• Xofigo is not recommended if the cancer in your bones is not causing symptoms, such as pain.
• Xofigo may cause a decrease in the number of blood cells and platelets in the blood.

Before starting treatment and before each subsequent dose, your doctor will perform a blood test.Based on the results of these tests, your doctor will decide whether treatment can start, continue, or should be delayed or stopped.

• If you have decreased production of blood cells in the bone marrow, e.g. if you have received chemotherapy (other medicines used to kill cancer cells) and/or radiation therapy, you may be at higher risk and your doctor will give you Xofigo with caution.

• If your tumour has spread extensively to the bone, you may be more likely to have a decrease in your blood cells and platelets, and your doctor will give you Xofigo with caution.
• There are limited data that do not suggest any important difference in blood cell production in patients who receive chemotherapy after Xofigo compared to those who do not receive Xofigo.

• There are no data on the use of Xofigo in patients with Crohn's disease(a long-term inflammatory disease of the intestines) and ulcerative colitis(a long-term inflammation of the colon). Due to the excretion of Xofigo in the faeces, Xofigo may worsen acute inflammation of the intestines. Therefore, if you have these diseases, your doctor will carefully consider whether you can be treated with Xofigo.
• If you have untreated or suspected spinal cord compression(pressure on the spinal cord nerves that can be caused by a tumour or other injury), your doctor will first treat this condition with standard treatment before starting or continuing treatment with Xofigo.
• If you have osteoporosis, or a known increased risk of fractures (e.g. recent bone fracture, fragility) or are taking or have taken corticosteroids(e.g. prednisone/prednisolone), please inform your doctor. You may be at higher risk of bone fractures. Your doctor may prescribe a medicine to prevent bone fractures before starting or continuing treatment with Xofigo.
• If you experience new or unusual painor swelling in a bone areabefore, during, or after treatment with Xofigo, talk to your doctor.
• If you have a bone fracture, your doctor will first stabilize the fractured bone before starting or continuing treatment with Xofigo.
• If you are taking or have taken bisphosphonatesor have received prior chemotherapy before Xofigo, inform your doctor. A risk of osteonecrosis of the jaw(dead tissue in the jawbone, mainly seen in patients who have been treated with bisphosphonates) cannot be excluded (see section 4).
• Xofigo contributes to your overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may increase your risk of developing cancer (in particular, bone cancer and leukaemia) and genetic abnormalities. No cases of cancer caused by Xofigo have been reported in clinical studies with up to three years of follow-up.

Your doctor will perform tests to determine the health of your bones before deciding whether you can receive Xofigo. During treatment and for 2 years after starting treatment with Xofigo, your doctor will continuously monitor the health of your bones.

Children and adolescents

This medicine is not intended for use in children and adolescents.

Other medicines and Xofigo

No studies have been performed on interactions with other medicines.

Xofigo must not be given in combination with abiraterone and prednisone/prednisolone due to a possible increased risk of bone fractures or deaths. Additionally, there are concerns about the effects of Xofigo when given with other systemic medicines used to treat prostate cancer that has spread. Inform your doctor if you are already taking any of these medicines.

If you are taking or have taken bisphosphonates or other medicines to protect the health of your bones or corticosteroids (e.g. prednisone/prednisolone) before Xofigo, inform your doctor. You may be at higher risk of bone fractures.

If you are taking calcium, phosphate, and/or vitamin D, your doctor will carefully consider whether you should temporarily stop taking these before starting treatment with Xofigo.

There are no data on the use of Xofigo at the same time as chemotherapy(other medicines used to kill cancer cells). The combined use of Xofigo and chemotherapy may further decrease the number of blood cells and platelets in the blood.

Tell your doctor if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

Pregnancy and breast-feeding

Xofigo must not be used in women and must not be given to women who are, or may be, pregnant or breast-feeding.

Contraceptive methods in women and men

If you have sexual intercourse with a woman who could become pregnant, you are advised to use effective contraceptive methods during treatment with Xofigo and for 6 months after treatment.

Fertility

There is a potential risk that the radiation emitted by Xofigo may affect your fertility. Ask your doctor how this may affect you, especially if you plan to have children in the future. If you wish, ask for advice on sperm preservation before starting treatment.

Driving and using machines

Xofigo is unlikely to affect your ability to drive or use machines.

Xofigo contains sodium

Depending on the volume administered, this medicine may contain up to 54 mg of sodium (a major component of cooking/table salt) per dose unit. This is equivalent to 2.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use Xofigo

There is strict legislation on the use, handling, and disposal of medicines like Xofigo. It will only be used in special controlled areas. This radiopharmaceutical will only be handled and administered by trained and qualified personnel in safe conditions. These personnel will take special care to use this radiopharmaceutical safely and will keep you informed of their actions.

The dose you receive will depend on your body weight. The doctor responsible for the procedure will calculate the amount of Xofigo to be used in your case.

The recommended amount of Xofigo is 55 kBq (Becquerel, the unit used to express radioactivity) per kilogram of body weight.

No dose adjustment is needed if you are 65 years of age or older or if you have reduced kidney or liver function.

Administration of Xofigo and procedure

Xofigo will be slowly injected through a needle inserted into one of your veins (intravenously). The healthcare professional will flush the intravenous access line or cannula before and after the injection with a sodium chloride solution.

Duration of the procedure

• Xofigo is given every 4 weeks for a total of 6 injections.

• There are no data available on the safety and efficacy of treatment with more than 6 injections of Xofigo.

After administration of Xofigo

• Be careful when handling materials such as bedding that come into contact with body fluids (e.g. urine spill, faeces, vomit, etc.). Xofigo is mainly excreted in the faeces. Your doctor will tell you if you need to take any special precautions after receiving this medicine. If you have any doubts, talk to your doctor.

If you are given more Xofigo than you should

Overdose is unlikely to occur. However, in case of accidental overdose, your doctor will start the relevant supportive treatment and examine you for changes in blood cell counts and gastrointestinal symptoms (e.g. diarrhoea, nausea [feeling sick], vomiting).

If you have any further questions on the use of Xofigo, ask the doctor responsible for the procedure.

4. Possible side effects

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

The most serious side effectsin patients treated with Xofigo are

• decrease in the number of platelets in the blood(thrombocytopenia),

• decrease in the number of neutrophils, a specific type of white blood cell(neutropenia, which can increase the risk of infection).

Contact your doctor immediately if you noticethe following symptoms, as they may be signs of thrombocytopenia or neutropenia (see above):

• any unusual bruising,

• bleedingmore than usual after an injury,
• fever,
• if you seem to be getting many infections.

Your doctor will perform blood tests before starting treatment and before each injection to check the number of blood cells and platelets (see also section 2).

The most common side effectsin patients treated with Xofigo (very common [may affect more than 1 in 10 people]) are:

• diarrhoea, nausea (feeling sick), vomiting, thrombocytopenia (decrease in the number of platelets in the blood), and bone fractures.

Risk of dehydration: tell your doctor if you have any of the following symptoms: dizziness, increased thirst, decreased urination (urine output) or dry skin, as these can be symptoms of dehydration. It is important to avoid dehydration by drinking plenty of fluids.

Other possible side effects are listed below by frequency:

Common(may affect up to 1 in 10 people)

• decrease in the number of white blood cells (leucopenia)
• decrease in the number of neutrophils, a specific type of white blood cell (neutropenia, which can increase the risk of infection)
• decrease in the number of red and white blood cells and platelets in the blood (pancytopenia)
• reactions at the injection site (e.g. skin redness [erythema], pain, and swelling)

Uncommon(may affect up to 1 in 100 people)

• decrease in the number of lymphocytes, a specific type of white blood cell (lymphopenia)
• weak bones (osteoporosis)

Xofigo contributes to your overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may increase your risk of developing cancer (in particular, bone cancer and leukaemia) and genetic abnormalities. No cases of cancer caused by Xofigo have been reported in clinical studies with up to three years of follow-up.

If you have symptoms of pain, swelling, or numbness of the jaw, a "heavy jaw feeling" or tooth loss, contact your doctor. Cases of osteonecrosis of the jaw(dead tissue in the jawbone, mainly seen in patients who have been treated with bisphosphonates) have occurred in patients treated with Xofigo. All these cases were only seen in patients who received bisphosphonates before or at the same time as Xofigo and chemotherapy before Xofigo.

Reporting of side effects

If you experience any side effects, talk to your doctor, 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 Xofigo

You will not need to store this medicine. This medicine is stored under the responsibility of the specialist in suitable facilities. The storage of radiopharmaceuticals will be carried out in accordance with national regulations on radioactive materials.

This information is intended only for the specialist:

Xofigo must not be used after the expiry date stated on the vial and lead container.

This medicine does not require any special storage temperature.

Do not use Xofigo if you notice discolouration, particles, or defects in the container.

6. Container contents and additional information

Xofigo composition

• The active ingredientis: radium chloride Ra 223 (223Ra) (radium chloride-223 (223Ra)). Each ml of solution contains 1100 kBq of radium chloride-223 (223Ra), corresponding to 0.58 ng of radium-223 on the calibration date. Each vial contains 6 ml of solution (6600 kBq of radium chloride-223 (223Ra) on the calibration date).
• The other componentsare: water for injectable preparations, sodium citrate, sodium chloride, and diluted hydrochloric acid (see the end of section 2 for additional information on sodium).

Product appearance and container contents

Xofigo is a clear and colorless injectable solution. It is supplied in a clear glass vial closed with a gray rubber stopper and an aluminum seal. The vial contains 6 ml of solution and is stored in a lead container.

Marketing authorization holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AS

Drammensveien 288

NO-0283 Oslo

Norway

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet {MM/YYYY}.

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

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This information is intended only for healthcare professionals:

The Summary of Product Characteristics or the Product Characteristics of Xofigo is included in its entirety in a section at the end of the printed leaflet in the product packaging, in order to provide healthcare professionals with additional scientific and practical information on the administration and use of this radiopharmaceutical.