Side Effects of Xofigo (radium Ra 223)

Xofigo (radium Ra 223) is a radioactive medicine used to treat male patients with advanced prostate cancer that has spread to the bones, but not to other parts of the body.

The radioactive particles emitted by Xofigo help kill cancer cells in the bone by damaging their DNA. Xofigo causes minimal damage to nearby healthy cells and can extend the lifespan of some patients.

Common side effects of Xofigo include:

• nausea,
• vomiting,
• diarrhea,
• swelling of the arms or legs, and
• low blood cell counts.

Serious side effects of Xofigo include:

• bone marrow suppression (a potentially serious condition in which blood cell counts decrease),
• a drop in red blood cells,
• white blood cells, and
• platelets.

Information on potential drug interactions with Xofigo is not available as no formal studies have been performed.

Xofigo can cause harm to a fetus and should not be used in women who are or may become pregnant. Pregnant or potentially pregnant women should not handle Xofigo without wearing gloves or proper protection. Male patients who are sexually active should use condoms and their female partners should use a highly effective method of birth control during treatment and for 6 months after stopping treatment.

Xofigo should not be used by women. It is not known if Xofigo is excreted in breast milk.

What are the important side effects of Xofigo (radium Ra 223)?

The most common side effects of radium Ra 223 are:

• nausea,
• vomiting,
• diarrhea,
• swelling of the arms or legs (peripheral edema), and
• low blood cell counts.

To avoid dehydration caused by diarrhea, nausea, or vomiting, patients are advised to drink plenty of water and report any signs of dehydration such as dry mouth or increased thirst.

Radium Ra 223 can cause bone marrow suppression, a potentially serious condition in which blood cell counts decrease.

In clinical studies, use of radium Ra 223 caused a drop in red blood cells, white blood cells, and platelets in some patients. Serious bone marrow problems led to treatment discontinuation, required blood transfusions, and some deaths.

Xofigo (radium Ra 223) side effects list for healthcare professionals

The following serious adverse reactions are discussed in greater detail in another section of the label:

• Bone Marrow Suppression

Clinical Trials Experience

In a randomized clinical trial in patients with metastatic castration-resistant prostate cancer with bone metastases:

• 600 patients received intravenous injections of Xofigo and best standard of care
• 301 patients received placebo and best standard of care once every 4 weeks for up to 6 injections.

Prior to randomization, a significant percentage of patients had received docetaxel in both arms. The median duration of treatment was 20 weeks for Xofigo and 18 weeks for placebo.

The most common adverse reactions in patients receiving Xofigo were:

• nausea,
• diarrhea,
• vomiting, and
• peripheral edema.

Grade 3 and 4 adverse events were reported among patients in both groups. The most common hematologic laboratory abnormalities in Xofigo-treated patients were:

• anemia,
• lymphocytopenia,
• leukopenia,
• thrombocytopenia, and
• neutropenia.

Treatment discontinuations due to adverse events occurred in a percentage of patients who received Xofigo. The most common hematologic laboratory abnormalities leading to discontinuation for Xofigo were anemia and thrombocytopenia.

Table 3: Adverse Reactions in the Randomized Trial

Laboratory Abnormalities

Table 4: Hematologic Laboratory Abnormalities

• Laboratory values were obtained at baseline and prior to each 4-week cycle.
• Grade 3-4 thrombocytopenia was reported in a percentage of patients on Xofigo and in a percentage of patients on placebo.
• Among patients who received Xofigo, grade 3-4 thrombocytopenia occurred in a percentage of docetaxel naive patients and in a percentage of patients who had received prior docetaxel.
• Grade 3-4 neutropenia occurred in a percentage of docetaxel naive patients and in a percentage of patients who have received prior docetaxel.

Fluid Status

• Dehydration occurred in a percentage of patients on Xofigo and in a percentage of patients on placebo.
• Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting which may result in dehydration.

Injection Site Reactions

Erythema, pain, and edema at the injection site were reported in a percentage of patients on Xofigo.

Secondary Malignant Neoplasms

• Xofigo contributes to a patient’s overall long-term cumulative radiation exposure.
• Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects.
• Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms.
• However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo.

Subsequent Treatment With Cytotoxic Chemotherapy

• In the clinical trial, a percentage of patients in both groups received cytotoxic chemotherapy after completion of study treatments.
• Adequate safety monitoring and laboratory testing were not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy.

What drugs interact with Xofigo (radium Ra 223)?

• No formal drug interaction studies have been performed.
• The concurrent use of bisphosphonates or calcium channel blockers did not affect the safety and efficacy of Xofigo in the clinical trial.

Summary

Xofigo (radium Ra 223) is a radioactive medicine used to treat male patients with advanced prostate cancer that has spread to the bones. Common side effects of Xofigo include nausea, vomiting, diarrhea, swelling of the arms or legs, and low blood cell counts. Effective birth control should be used by both male and female partners during treatment. Xofigo should not be used by women and its excretion in breast milk is unknown.