Xofigo 1100 kBq/ml solution for injection

Patient Information Leaflet

Introduction

Package Leaflet: Information for the patient

Xofigo 1100 kBq/ml solution for injection

radium dichloride Ra 223 (223Ra)

This medicinal product is subject to additional monitoring, which will enable rapid identification of new safety information. You can help by reporting any side effects you may experience. Section 4 includes information on how to report side effects.

Read this leaflet carefully before you are given this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor, who will supervise the procedure.

• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Xofigo is and what it is used for

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

3. How to use Xofigo

4. Possible side effects

5. How to store Xofigo

6. Contents of the pack and other information

1. What Xofigo is and what it is used for

This medicine contains the active substance radium Ra 223 dichloride (223Ra) (radium-223 dichloride (223Ra)).

Xofigo is used to treat adult men with advanced castration-resistant prostate cancer that is progressing after at least two other cancer treatments apart from treatments to maintain low levels of male hormones (hormonal therapy), or in patients who cannot receive any other cancer treatment. Castration-resistant prostate cancer is a prostate cancer (a gland in the male reproductive system) that no longer responds to treatments that reduce male hormones. Xofigo is used only when the disease has spread to the bones, but is not known to have spread to other internal organs, and is causing symptoms (for example, pain).

Xofigo contains the radioactive substance radium-223 (223Ra), which mimics calcium found in bones. When injected into the patient, radium-223 (223Ra) travels to the bone areas where cancer has spread and emits short-range radiation (alpha particles), which destroys surrounding tumor cells.

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 for the treatment of 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 death. In addition, there are concerns about the effects of Xofigo when used in combination with other medicines used to treat metastatic prostate cancer. Inform your doctor if you are already taking any of these medicines.

• If you are scheduled 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 scheduled to receive another treatment for cancer after treatment with Xofigo, you must wait at least 30 days before starting that treatment.

• The use of 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 be started, continued, postponed, or stopped.

• If you have a reduced production of blood cells in the bone marrow, e.g., if you have previously 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 cancer has spread extensively to the bones, you may be more likely to experience a reduction in blood cells and platelets, so your doctor will give you Xofigo with caution.

• Limited data are available, which do not suggest any important difference in blood cell production in patients receiving chemotherapy after Xofigo treatment compared to those not receiving Xofigo.

• There is no data available on the use of Xofigo in patients with Crohn's disease (a long-term inflammatory disease of the intestines) or ulcerative colitis (long-term inflammation of the colon). Because Xofigo is excreted in faeces, Xofigo may worsen acute intestinal inflammation. Therefore, if you have these conditions, your doctor will carefully assess whether you can be treated with Xofigo.

• If you have untreated spinal cord compression or if spinal cord compression (pressure on the nerves of the spinal cord, possibly caused by a tumour or other injury) is suspected, your doctor will first treat this condition with standard therapy 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 or have been taking 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 pain or swelling in a bone area before, during, or after treatment with Xofigo, consult your doctor.

• If you suffer 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 bisphosphonates or have received prior chemotherapy before treatment with Xofigo, inform your doctor. A risk of osteonecrosis of the jaw (dead bone tissue in the jawbone, mainly observed in patients 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 (specifically bone cancer and leukaemia) and heritable 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 assess the health of your bones before deciding whether you can receive Xofigo. During treatment and for 2 years after starting 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 interaction studies with other medicines have been conducted.

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

If you are or have been taking bisphosphonates or other medicines to protect bone health or corticosteroids (e.g., prednisone/prednisolone) before treatment with Xofigo, please 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 them before starting treatment with Xofigo.

There is no data available 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 reduce the number of blood cells and platelets in the blood.

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

Pregnancy and breastfeeding

Xofigo must not be used in women and must not be given to women who are or may be pregnant or breastfeeding.

Contraception in women and men

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

Fertility

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

Driving and use of machines

Xofigo is considered 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 main component of table/cooking salt) per dose unit. This is equivalent to 2.7% of the maximum daily intake of sodium recommended for an adult.

3. How to use Xofigo

There is strict legislation regarding the use, handling, and disposal of medications such as Xofigo. It will only be used in specially controlled areas. This radiopharmaceutical will be handled and administered solely by trained and qualified personnel who are skilled in its safe use. These individuals will take special care to ensure the safe use of this radiopharmaceutical and will keep you informed about their actions.

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

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

Dose adjustment is not necessary if you are 65 years of age or older, or if you have reduced renal or hepatic 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 line or cannula with a sodium chloride solution before and after the injection.

Duration of treatment

• Xofigo is administered every 4 weeks, up to a total of 6 injections.

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

After administration of Xofigo

• Care should be taken when handling materials such as bed linens that may come into contact with bodily fluids (such as urine spillage, feces, vomit, etc.). Xofigo is primarily excreted in feces. Your physician will advise you if any special precautions are needed after receiving this medication. If you have any doubts, consult your physician.

If you have been given more Xofigo than you should

An overdose is unlikely to occur. However, in the event of accidental overdose, your physician will initiate appropriate supportive treatment and monitor you for changes in blood cell counts and gastrointestinal symptoms (e.g., diarrhea, nausea [feeling of wanting to vomit], vomiting).

If you have any further questions about the use of Xofigo, please ask the physician responsible for supervising the procedure.

4. Possible side effects

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

The most serious side effects in 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 cells (neutropenia, which may lead to an increased risk of infection).

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

• any unusual bruising,

• increased bleeding after an injury,

• fever,

• if you seem to get many infections.

Your doctor will perform blood tests before starting treatment and before each injection to monitor your blood cell and platelet counts (see also section 2).

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

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

Risk of dehydration: inform your doctor if you experience any of the following symptoms: dizziness, increased thirst, reduced urination, or dry skin, as these may be signs of dehydration. It is important to prevent dehydration by drinking plenty of fluids.

Other possible side effects are listed below by their frequency:

Common (may affect up to 1 in 10 people)

• decrease in the number of white blood cells (leukopenia)
• decrease in the number of neutrophils, a specific type of white blood cells (neutropenia, which may lead to an increased 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 cells (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 (specifically bone cancer and leukemia) and hereditary abnormalities. Cases of cancer caused by Xofigo have not been reported in clinical studies with up to three years of follow-up.

If you have symptoms of pain, swelling, or numbness in the jaw, a "heavy jaw sensation," or tooth loss, contact your doctor. Cases of osteonecrosis of the jaw (dead bone tissue in the jaw, observed mainly in patients who have been treated with bisphosphonates) have occurred in patients treated with Xofigo. All such cases occurred only in patients who had received bisphosphonates before or during treatment with Xofigo and chemotherapy prior to treatment with Xofigo.

Reporting of side effects

If you get any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report them directly through 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 be responsible for storing this medicine. This medicine is stored under the supervision of a specialist in appropriate facilities. Storage of radiopharmaceuticals must comply with national regulations regarding radioactive materials.

This information is intended for healthcare professionals only:

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 discoloration, presence of particles, or defects in the container are observed.

6. Contents of the container and other information

Composition of Xofigo

• The active substance is: radium dichloride Ra 223 (223Ra) (radium-223 dichloride (223Ra)). Each ml of solution contains 1100 kBq of radium-223 dichloride (223Ra), equivalent to 0.58 ng of radium-223 at the calibration date. Each vial contains 6 ml of solution (6600 kBq of radium-223 dichloride (223Ra) at the calibration date).
• The other components are: water for injections, sodium citrate, sodium chloride and diluted hydrochloric acid (see the end of section 2 for additional information on sodium).

Appearance of the product and contents of the container

Xofigo is a clear, colourless injectable solution. It is supplied in a colourless glass vial closed with a grey rubber stopper and an aluminium seal. The vial contains 6 ml of solution and is stored in a lead container.

Marketing Authorization Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer responsible

Bayer AS

Drammensveien 288

NO-0283 Oslo

Norway

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: {MM/YYYY}.

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

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This information is intended for healthcare professionals only:

The Summary of Product Characteristics (SmPC) for Xofigo is included in its complete version 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.