Xofigo

Package leaflet: Information for the patient

Xofigo 1 100 kBq/mL solution for injection

radio Ra 223 dichloride
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult the doctor responsible for supervising the procedure.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

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

1. What Xofigo is and what it is used for

This medicinal product contains the radioactive active substance Ra 223 dichloride (radium-223 dichloride).
Xofigo is used to treat adult patients with advanced prostate cancer that is castration-resistant and has progressed after at least two other anticancer treatments, in addition to treatments aimed at reducing male hormone levels (hormonal therapy), or in patients who cannot receive other anticancer treatments. Castration-resistant prostate cancer is a tumour of the prostate (a gland of the male reproductive system) that no longer responds to treatments that lower male hormone levels. Xofigo is used only when the disease has spread to the bones and is causing symptoms (e.g. pain), and there is no known spread to other internal organs.
Xofigo contains the radioactive substance radium-223, which mimics calcium found in bones. Once injected into the patient, radium-223 travels to the bone areas affected by the tumour and emits short-range radiation (alpha particles), which kill surrounding cancer cells.

2. What you should know before using Xofigo

Xofigo must not be administered

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

Warnings and precautions
Talk to your doctor before receiving Xofigo.

• Xofigo must not be administered in combination with abiraterone and prednisone/prednisolone due to a possible increased risk of bone fractures or death. In addition, there are uncertainties regarding the effects of Xofigo when used in combination with other medicines used to treat metastatic prostate cancer. If you are already taking one of these medicines, inform your doctor.
• If you are planning to receive Xofigo after treatment with abiraterone and prednisone/prednisolone, you must wait 5 days before starting treatment with Xofigo.
• If you are planning to receive another anticancer therapy after treatment with Xofigo, you must wait at least 30 days before starting that treatment.
• Xofigo is not recommended if bone cancer is not causing any symptoms, such as pain.
• Xofigo may reduce the number of blood cells and platelets in your blood. Before starting treatment and before each subsequent dose, your doctor will perform blood tests. Based on the results of these tests, your doctor will decide whether treatment can begin or continue, or whether it should be delayed or stopped.
• If you have reduced blood cell production in the bone marrow, for example if you have previously undergone chemotherapy (other medicines used to kill cancer cells) and/or radiotherapy, you may be at higher risk and your doctor will administer Xofigo with caution.
• If cancer has spread extensively to the bones, it is very likely that you will experience a decrease in blood cells and platelets, so your doctor will administer Xofigo with caution.
• Limited available data do not suggest major differences in blood cell production between patients who received chemotherapy after Xofigo treatment and those who did not receive Xofigo.
• There are no data on the use of Xofigo in patients with Crohn’s disease (a chronic inflammatory bowel disease) or ulcerative colitis (chronic inflammation of the colon). Since Xofigo is excreted in faeces, it may worsen acute intestinal inflammation. Therefore, if you have these conditions, your doctor will carefully evaluate whether you can be treated with Xofigo.
• If you have untreated spinal cord compression or are likely to develop spinal cord compression (pressure on the nerves of the spinal cord that may be caused by a tumour or other lesion), 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 taking or have taken steroids (e.g. prednisone/prednisolone), 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 the bone area before, during, or after treatment with Xofigo, you must consult 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 bisphosphonates or have received 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 ruled out (see section 4).
• Xofigo contributes to the overall long-term cumulative exposure to radiation. Long-term cumulative exposure to radiation may increase the risk of developing malignant tumours (particularly bone tumours and leukaemia) and heritable genetic defects. No cases of tumours caused by Xofigo have been reported in clinical studies where patients were followed for up to three years after study completion.

Your doctor will assess your bone health before deciding whether you can receive Xofigo. During treatment and for 2 years after starting Xofigo, your doctor will continuously monitor your bone health.
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 administered in combination with abiraterone and prednisone/prednisolone due to a possible increased risk of bone fracture or death. In addition, there are uncertainties regarding the effects of Xofigo in combination with other systemic medicines used to treat metastatic prostate cancer. If you are already taking one of these medicines, inform your doctor.
If you are taking or have taken bisphosphonates or other medicines to protect bone health, or steroids (e.g. prednisone/prednisolone) before treatment with Xofigo, inform your doctor. You may be at higher risk of bone fractures.
If you are taking calcium, phosphates, and/or vitamin D, your doctor will carefully assess whether it is necessary to temporarily discontinue these substances before starting treatment with Xofigo.
There are no data on the use of Xofigo concomitantly with chemotherapy (other medicines used to kill cancer cells).
When used together, 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 take any other medicines, including those without a prescription.
Pregnancy and breastfeeding
Xofigo is not indicated for women and must not be administered to women who are, or may be, pregnant or breastfeeding.
Contraception in men and women
If you have sexual intercourse with a woman who could become pregnant, you must use effective contraception during treatment with Xofigo and for 6 months after.
Fertility
There is a potential risk that radiation from Xofigo may affect fertility. Discuss this with your doctor, especially if you plan to have children in the future. You may wish to consider sperm preservation before starting treatment.
Driving and using machines
Xofigo is considered unlikely to impair your ability to drive vehicles or operate machinery.
Xofigo contains sodium
Depending on the volume administered, this medicine may contain up to 54 mg of sodium (a main component of table salt) per dose. This corresponds to 2.7% of the maximum daily dietary intake recommended for an adult.

3. How Xofigo is used

There are strict regulations regarding the use, handling, and disposal of medicinal products similar to Xofigo. This
radiopharmaceutical will be used only in designated controlled areas and will be handled and administered
exclusively by qualified and trained personnel experienced in the safe use of such agents. These individuals
will pay particular attention to the safe use of this radiopharmaceutical and will inform you about how the
procedure will be carried out.
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 dose of Xofigo is 55 kBq (Becquerel, the unit of measurement of radioactivity) per
kilogram of body weight.
Dose adjustment is not required if you are 65 years of age or older, or if you have reduced kidney or
liver function.

Administration of Xofigo and conduct of the procedure
Xofigo will be slowly injected through a needle into a vein. The healthcare professional will flush the intravenous access or catheter with a sodium chloride solution before and after the injection.

Duration of the procedure

• Xofigo is administered once every 4 weeks, for a total of 6 injections.
• There are no data available on the efficacy and safety of treatment with Xofigo beyond 6 injections.

After administration of Xofigo

• Care should be taken when handling materials such as bed linen that may come into contact with bodily fluids (e.g., splashes of urine, faeces, vomit, etc.). Xofigo is mainly excreted in faeces. Your doctor will advise you whether specific precautionary measures are necessary after administration of the medicine. If you have any doubts, consult your doctor.

If you have received more Xofigo than you should
Overdose is unlikely.
However, in case of accidental overdose, the doctor will initiate appropriate supportive treatment and
monitor for changes in blood cell counts or gastrointestinal symptoms (such as diarrhoea, nausea, vomiting).
If you have any questions about the use of Xofigo, consult the doctor responsible for supervising the
procedure.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The most serious side effects in patients treated with Xofigo are:

• reduction in the number of platelets in the blood (thrombocytopenia),
• reduction in the number of neutrophils, a specific type of white blood cells (neutropenia, which may increase the risk of infections).

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

• any unusual bruising,
• bleeding that is heavier than usual after an injury,
• fever,
• or if you are experiencing infections more frequently than usual.

Your doctor will carry out certain blood tests before starting treatment and before each injection
to monitor the number of blood cells and platelets (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:

• diarrhoea, nausea (feeling unwell), vomiting, thrombocytopenia (reduction in the number of platelets in the blood), and bone fractures

Risk of dehydration: inform your doctor if you have any of the following symptoms: dizziness, increased thirst,
decreased urine output, or dry skin, as these may 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)

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

Uncommon (may affect up to 1 in 100 people)

• reduction in the number of lymphocytes, a specific type of white blood cells (lymphopenia)
• weakening of the bones (osteoporosis)

Xofigo contributes to the long-term cumulative global exposure to radiation. Long-term cumulative exposure to radiation may increase the risk of developing malignant tumours (particularly bone tumours and leukaemia) and heritable genetic defects. No cases of tumours caused by Xofigo have been reported in clinical studies where patients were followed for up to three years after study completion.
If you experience pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth, contact your doctor. Cases of osteonecrosis of the jaw (dead bone tissue in the jawbone, observed mainly in patients treated with bisphosphonates) have been observed in patients treated with Xofigo. All these cases occurred in patients who had previously or concurrently received bisphosphonates along with chemotherapy prior to treatment with Xofigo.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your doctor. 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 Xofigo is stored

It is not your responsibility to store this medicine. This medicine will be stored under the supervision of a specialist in appropriate facilities. Storage of radiopharmaceuticals will be carried out in accordance with national regulations concerning radioactive materials.

The following information is intended for healthcare professionals only:

Xofigo must not be used after the expiry date stated on the vial and lead container.
This medicinal product does not require any specific storage temperature.
Xofigo must not be used if there is discoloration, presence of particles, or if the container is damaged.

6. Package contents and other information

What Xofigo contains

• The active substance is radium Ra 223 dichloride (radium-223 dichloride).

Each mL of solution contains 1,100 kBq of radium-223 dichloride, corresponding to 0.58 ng of radium-223 at the reference date.
Each vial contains 6 mL of solution (6,600 kBq of radium-223 dichloride at the reference date).

• The other components are water for injections, sodium citrate, sodium chloride, and diluted hydrochloric acid (see the end of section 2 for further information on sodium).

Description of the appearance of Xofigo and contents of the pack
Xofigo is a clear, colourless injectable solution. It is supplied in a colourless glass vial sealed with a grey rubber stopper and an aluminium cap. The vial contains 6 mL of solution and is placed in a lead container.
Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany
Manufacturer
Bayer AS
Drammensveien 288
NO-0283 Oslo
Norway
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België / Belgique / Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel. +37 05 23 36 868
България Luxembourg / Luxemburg
Байер България ЕООД Bayer SA-NV
Тел. +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11
Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420 266 101 111 Tel.: +36 14 87-41 00
Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45-45 23 50 00 Tel: +35 621 44 62 05
Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49 (0)214-30 513 48 Tel: +31-23–799 1000
Eesti Norge
Bayer OÜ Bayer AS
Tel: +372 655 8565 Tlf. +47 23 13 05 00
Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges. m. b. H.
Τηλ: +30 210 61 87 500 Tel: +43-(0)1-711 46-0
España Polska
Bayer Hispania S.L. Bayer Sp. z o.o.
Tel: +34-93-495 65 00 Tel.: +48 22 572 35 00
France Portugal
Bayer HealthCare Bayer Portugal, Lda.
Tél(N° vert): +33-(0)800 87 54 54 Tel: +351 21 416 42 00
Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: + 385-(0)1-6599 900 Tel: +40 21 529 59 00
Ireland Slovenija
Bayer Limited Bayer d. o. o.
Tel: +353 1 216 3300 Tel.: +386 (0)1 58 14 400
Ísland Slovenská republika
Icepharma hf. Bayer, spol. s r.o.
Sími: +354 540 8000 Tel: +421 2 59 21 31 11
Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39 02 397 81 Puh/Tel: +358 20 785 21
Κύπρος Sverige
NOVAGEM Limited Bayer AB
Τηλ: +357 22 48 38 58 Tel: +46 (0) 8 580 223 00
Latvija
SIA Bayer
Tel: +371 67 84 55 63

This leaflet was last updated
More 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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The following information is intended for healthcare professionals only.
The complete Summary of Product Characteristics (SmPC) for Xofigo is provided as a detachable section at the end of the package leaflet, aimed at providing healthcare professionals with additional scientific and practical information on the administration and use of this radiopharmaceutical product.