Class: Radiopharmaceutical

Generic Name: Radium Ra 223 dichloride (RAY-dee-um Ra 223 dye-KLOR-ide)

Trade Name: Xofigo®

For which conditions is this drug approved? Radium Ra 223 dichloride is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease.

What is the mechanism of action? The active component of radium Ra 223 dichloride is the alpha particle-emitting isotope radium-223 (as radium Ra 223 dichloride), which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases The high linear energy transfer of alpha emitters (80 keV/micrometer) leads to a high frequency of double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium-223 dichloride is less than 100 micrometers (less than 10 cell diameters), which limits damage to the surrounding normal tissue.

How is radium Ra 223 dichloride typically given (administered)? Radium Ra 223 dichloride is administered by slow intravenous injection over 1 minute. Dosage is determined by body weight (50 kBq [1.35 microcurie] per kg body weight) and given at four-week intervals for six injections. Safety and efficacy beyond six injections have not been studied.

How are patients typically monitored? Patients will usually have scheduled meetings with their healthcare provider while they are being treated with radium Ra 223 dichloride. Typically, blood will be drawn to check levels of blood cells and to monitor functions of some organ systems, such as the kidneys or liver.  Patients may also undergo physical examinations, scans or other measures to assess side effects and response to therapy.

In addition, patients will have blood counts measured prior to treatment initiation and before every dose of radium Ra 223 dichloride. Physicians are advised to discontinue treatment if hematologic values do not recover within six to eights weeks after treatment. Patients with compromised bone marrow reserve should be monitored closely, and radium Ra 223 dichloride should be discontinued in patients who experience life-threatening complications despite supportive care measures.

What are the common (occur in 30% or more of patients) side effects of treatment with radium Ra 223 dichloride?

• Nausea
• Anemia
• Lymphocytopenia (insufficient white blood cell counts)
• Leukopenia (low white blood cell counts)
• Thrombocytopenia (abnormally low amount of platelets)

What are the less common (occur in 10% to 29% of patients) side effects of treatment with radium Ra 223 dichloride?

• Diarrhea
• Vomiting
• Peripheral edema (swelling of ankles, feet, and legs)
• Neutropenia (low neutrophil count, a type of white blood cell that helps fight infection)

This is not a complete list of side effects. Some patients may experience other side effects that are not listed here. Patients may wish to discuss with their physician the other less common side effects of this drug, some of which may be serious.

Some side effects may require medical attention. Other side effects do not require medical attention and may go away during treatment. Patients should check with their physician about any side effects that continue or are bothersome.

What can patients do to help alleviate or prevent discomfort and side effects?

• Pay careful attention to the physician’s instructions and inform the physician of any side effects.
• Maintain adequate rest and nutrition.
• Eat small meals frequently to help alleviate nausea.
• If patients have been prescribed an anti-nausea medication, they should be sure to take the prescribed doses.
• Have blood cell count monitored while receiving radium Ra 223 dichloride.
• Drink plenty of fluids. (Patients should ask their physician about the amount of liquid to consume during a day.)
• If possible, avoid large crowds or people who are sick or not feeling well, as this drug may leave some patients susceptible to infection.
• Wash hands often to reduce the risk of infection.
• Avoid activities that may cause injury or bruising.
• Use a soft toothbrush and an electric razor to prevent cuts on the mouth or skin.

Are there any special precautions patients should be aware of before starting treatment?

• There are no restrictions regarding contact with other people after receiving radium Ra 223 dichloride, but patients should follow good hygiene practices while receiving this drug and for at least one week after the last injection in order to minimize radiation exposure from bodily fluids to household members and caregivers. Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. Clothing soiled with patient fecal matter or urine should be washed promptly and separately from other clothing. Caregivers should use universal precautions for patient care such as gloves and barrier gowns when handling bodily fluids to avoid contamination.
• Patients who are sexually active should use condoms and their female partners of reproductive potential should use a highly effective method of birth control during treatment and for six months following completion of treatment.

When should patients notify their physician?

• If there are signs of bleeding or infection
• If there are signs of dehydration, hypovolemia (decreased blood volume), urinary retention, or renal failure/insufficiency

What is a package insert?
A package insert is required by the FDA and contains a summary of the essential scientific information needed for the safe and effective use of the drug for healthcare providers and consumers.  A package insert typically includes information regarding specific indications, administration schedules, dosing, side effects, contraindications, results from some clinical trials, chemical structure, pharmacokinetics and metabolism of the specific drug. By carefully reviewing the package insert, you will get the most complete and current information about how to safely use this drug. If you do not have the package insert for the drug you are using, your pharmacist or physician may be able to provide you with a copy.