Xofigo 1100 kBq/mL solution for injection

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor who will supervise the procedure.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Xofigo is and what it is used for
2. What you need to know before Xofigo is used
3. How Xofigo is used
4. Possible side effects
5. How Xofigo is stored
6. Contents of the pack and other information

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

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 increase in the risk of bone fracture or death. Additionally, there are uncertainties about the effects of Xofigo in combination with other medicines used to treat metastatic prostate cancer. If you are already taking one of those medicines, please tell your doctor.
• If you plan to take Xofigo following treatment with abiraterone and prednisone/prednisolone, you must wait 5 days before starting treatment with Xofigo.
• If you plan to take other cancer therapy following treatment with Xofigo, you must wait at least 30 days before starting treatment.
• Xofigo is not recommended if cancer in your bones is not causing symptoms, such as pain.
• Xofigo can lead to a decrease in the number of your blood cells and blood platelets. Before starting treatment and before each subsequent dose your doctor will perform blood tests. Depending on the results of these tests your doctor will decide if treatment can be started, can be continued, or needs to be postponed or discontinued.
• If you suffer from decreased blood cell production in the bone marrow, e.g., if you have received prior 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 to the bone extensively, you may also be more likely to have decreases in your blood cells and platelets, so your doctor will give you Xofigo with caution.
• The limited data available do not suggest any major differences in the blood cell production of patients receiving chemotherapy after treatment with Xofigo compared with those who did 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 with ulcerative colitis (a long-term inflammation of the colon). As Xofigo is excreted in the faeces, it may make acute inflammation of your bowels worse. Therefore, if you suffer from these conditions your doctor will carefully consider if you can be treated with Xofigo.
• If you suffer from untreated spinal cord compression or if it is thought likely that you are developing spinal cord compression (pressure on the spinal cord nerves which can be caused by a tumour or other lesion), your doctor will first treat this disease with standard treatment before starting or continuing treatment with Xofigo.
• If you have osteoporosis or a known increased risk for fractures (e.g., recent bone fracture, fragility), or take or have been taking steroids (e.g., prednisone/prednisolone), please tell your doctor. You might be at a higher risk of bone fractures. Your doctor might prescribe you a medicine to prevent bone fractures before starting or continuing treatment with Xofigo.
• If you experience any new or unusual pain or swelling in bone region prior, during or after your treatment with Xofigo, you should consult your doctor.
• If you experience a bone fracture, your doctor will first stabilise the fractured bone before starting or continuing treatment with Xofigo.
• If you take or have taken bisphosphonates or have received chemotherapy prior to treatment with Xofigo, please tell your doctor. A risk of osteonecrosis of the jaw (dead tissue in the jawbone which is 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 for developing cancer (in particular of bone cancer and leukaemia) and hereditary abnormalities. No cases of cancer caused by Xofigo have been reported in clinical studies with a follow-up of up to three years.

Your doctor will test your bone health before deciding whether you can be given Xofigo. During treatment and for 2 years after starting treatment with Xofigo, your doctor will continuously monitor your bone health.

This medicine is not for use in children and adolescents.

No interaction studies with other medicines have been done.

Xofigo must not be given in combination with abiraterone and prednisone/prednisolone due to a possible increase in the risk of bone fracture or death. Additionally, there are uncertainties about the effects of Xofigo in combination with other systemic medicines used to treat metastatic prostate cancer. If you are already taking one of those medicines, please tell your doctor.

If you take or have taken bisphosphonates or other medicines to protect your bone health or steroids (e.g., prednisone/prednisolone) prior to treatment with Xofigo, please tell your doctor. You might be at a higher risk for bone fractures.

If you are taking calcium, phosphate and/or Vitamin D, your doctor will carefully consider if you need to temporarily stop taking these substances before you start 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). Xofigo and chemotherapy used together may further decrease the number of your blood cells and blood platelets.

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

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

If you are engaged in sexual activity with a woman who could become pregnant you are advised to use effective birth control methods during and up to 6 months after treatment with Xofigo.

There is a potential risk that radiation from Xofigo could affect your fertility. Please ask your doctor how this may affect you, especially if you are planning to have children in the future. You may wish to seek advice on conservation of sperm before treatment starts.

It is considered unlikely that Xofigo will affect your ability to drive or to use machines.

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

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

• Xofigo is given once 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.

• Care should be taken when handling materials, such as bed linen, that come into contact with body fluids (such as spill of urine, faeces, vomiting etc.). Xofigo is excreted mainly via the faeces. The doctor will tell you if you need to take any special precautions after receiving this medicine. Contact your doctor if you have any questions.

An overdose is unlikely.

However, in the case of an accidental overdose, your doctor will start appropriate supportive treatment and will check you for changes in the number of blood cells, and for gastrointestinal symptoms (e.g. diarrhoea, nausea [feeling sick], vomiting).

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 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 blood platelets (pancytopenia)
• injection site reactions (e.g. redness of the skin [erythema], pain and swelling)

Uncommon (may affect up to 1 in 100 people)

• decrease in the number of lymphocytes, a type of white blood cells (lymphopenia)
• weakened 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 of bone cancer and leukaemia) and hereditary abnormalities. No cases of cancer caused by Xofigo have been reported in clinical studies with a follow-up of up to three years.

If you have symptoms of pain, swelling or numbness of the jaw, a “heavy jaw feeling” or loosening of a tooth, please contact your doctor. Cases of osteonecrosis of the jaw (dead tissue in the jawbone which is 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 receiving bisphosphonates prior to or at the same time of treatment with Xofigo and chemotherapy prior to treatment with Xofigo.

If you get any side effects talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

Xofigo must not be used after the expiry date which is stated on the vial and the lead pot.

This medicine does not require any special temperature storage conditions.

Xofigo must not be used if discolouration, the occurrence of particulate matter or a defective container is noticed.

• The active substance is: radium Ra 223 dichloride (radium-223 dichloride).
  Each mL of solution contains 1100 kBq radium-223 dichloride, corresponding to 0.58 ng radium-223 at the reference date.
  Each vial contains 6 mL of solution (6600 kBq radium-223 dichloride at the reference date).
• The other ingredients are: water for injections, sodium citrate, sodium chloride and diluted hydrochloric acid (see end of Section 2 for further information on sodium).

Xofigo is a clear and colourless solution for injection. It is supplied in a colourless glass vial closed with a grey rubber stopper and aluminium seal. The vial contains 6 mL of solution. It is stored in a lead pot.