Xofigo

Other Therapeutic Radiopharmaceuticals

Radium-223 dichloride (an alpha particle-emitting pharmaceutical) should only be received, used and administered by authorized persons in designated clinical settings, and is subject to the regulations and/or appropriate licenses of the competent official organization.

Radium-223 dichloride is available in 6 mL single use vials containing 1,100 kBq/mL (30 microcurie/mL) at the reference date.
Use universal precautions to avoid contamination, including gloves and barrier gowns, when handling blood and body fluids. Minimize the time spent in radiation areas, maximize the distance to radiation sources, and use adequate shielding
In case of exposure to skin or eyes, flush immediately with water.
In case of a spill, contact the local radiation safety officer immediately to begin decontamination procedures. Ethylene-diaminetetraacetic acid (EDTA, 0.01M) is recommended to remove contamination.
There is a risk for radiation exposure or contamination from spills of bodily fluids (e.g., feces, urine, and vomit). Medical staff, caregivers, and patient's household members should take appropriate radiation protection precautions, including multiple flushes after using the toilet, washing soiled clothing separately from other clothing, and wearing gloves when handling body fluids.
Do not mix or dilute radium-223 dichloride with other solutions.
Dispose of any unused product or contaminated materials in accordance with local regulations on radioactive waste.

Use aseptic technique during preparation and administration, as well as appropriate precautions for radiopharmaceuticals.
Visually inspect product for particulate matter and discoloration.
Flush the line with isotonic saline before and after administration.
Administer as a slow intravenous injection over 1 minute.

new primary malignancy / Delayed / 0-1.0
nausea / Early / 2.0
diarrhea / Early / 2.0
vomiting / Early / 2.0
peripheral edema / Delayed / 2.0
infection / Delayed / 2.0

dehydration / Delayed / 3.0
erythema / Early / 1.0

injection site reaction / Rapid / 1.0

Xofigo

Rx

Alpha-particle emitting radiotherapeutic drug
Used for the treatment of castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease
Bone marrow failure may occur; hematologic evaluation should be performed prior to each dose.

55 Kilobecquerel (kBq) (equal to 1.49 microcurie) per kg of body weight by slow IV injection over 1 minute, every 4 weeks for 6 injections. The safety and efficacy beyond 6 injections has not been studied. When calculating the dose, a decay correction factor must be used to account for the physical decay of radium-223 after packaging (see below). Immediately before and after administration, measure the net patient dose in a radioisotope dose calibrator that has been calibrated with a National Institute of Standards and Technology (NIST) traceable radium-223 standard and corrected for decay using the date and time of calibration. After initial calibration, re-calibrate the dose calibrator at least yearly, and after any maintenance that could affect the dosimetry.
Volume to be administered (mL) = Body weight in kg x 55 kBq/kg
                                                  Decay factor x 1,100 kBq/mL
or
Volume to be administered (mL) = Body weight in kg x 1.49 microcurie/kg
                                                  Decay factor x 30 microcurie/mL
Number of days from reference date on vial (Decay factor)
-14 (2.296)     0 (0.982)
-13 (2.161)     1 (0.925)
-12 (2.034)     2 (0.87)
-11 (1.914)     3 (0.819)
-10 (1.802)     4 (0.771)
-9 (1.696)      5 (0.725)
-8 (1.596)      6 (0.683)
-7 (1.502)      7 (0.643)
-6 (1.414)      8 (0.605)
-5 (1.33)        9 (0.569)
-4 (1.252)      10 (0.536)
-3 (1.178)      11 (0.504)
-2 (1.109)      12 (0.475)
-1 (1.044)      13 (0.447)
                     14 (0.42)

Since radium-223 dichloride is not metabolized in the liver and does not undergo biliary excretion, it does not appear that hepatic impairment should affect the pharmacokinetics. A dedicated trial in patients with hepatic impairment has not been conducted; however, based on a subgroup analysis in the randomized clinical trial, dose adjustment is not needed in patients with mild hepatic impairment. Insufficient data exists to make a recommendation in patients with moderate or severe hepatic impairment.

A dedicated trial in patients with renal impairment has not been conducted; however, based on a subgroup analysis in the randomized clinical trial, dose adjustment is not needed in patients with mild or moderate renal impairment (CrCL greater than or equal to 30 mL/min). Insufficient data exists to make a recommendation in patients with severe renal impairment (CrCL less than 30 mL/min).

Abiraterone: (Major) Radium RA 223 dichloride is not recommended for use in combination with abiraterone plus prednisone or prednisolone outside of clinical trials. The risk of fractures (28.6% vs. 11.4%) and death (38.5% vs. 35.5%) was increased with the use of Radium RA 223 dichloride compared with placebo, both in combination with abiraterone and prednisone/prednisolone, in a randomized phase 3 trial. The safety and efficacy of Radium RA 223 dichloride and agents other than gonadotropin-releasing hormone analogues have not been established.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Niraparib; Abiraterone: (Major) Radium RA 223 dichloride is not recommended for use in combination with abiraterone plus prednisone or prednisolone outside of clinical trials. The risk of fractures (28.6% vs. 11.4%) and death (38.5% vs. 35.5%) was increased with the use of Radium RA 223 dichloride compared with placebo, both in combination with abiraterone and prednisone/prednisolone, in a randomized phase 3 trial. The safety and efficacy of Radium RA 223 dichloride and agents other than gonadotropin-releasing hormone analogues have not been established.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.

Xofigo Intravenous Inj Sol: 1mL, 1100kBq

55 kBq/kg (1.49 microcurie/kg).

55 kBq/kg (1.49 microcurie/kg).

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Radium-223 dichloride is an alpha particle-emitting radiopharmaceutical administered via intravenous injection. When new bone formation occurs around bone metastases, radium-223 dichloride mimics calcium to form complexes with hydroxyapatite, a calcium-containing component of the bone matrix, at areas of increased bone turnover such as bone metastases. Once incorporated into the bone matrix, the high linear energy transfer of alpha particles (80 keV/micrometer) leads to a high frequency of double-strand DNA breaks in adjacent cells including tumor cells, osteoblasts, and osteoclasts, resulting in an anti-tumor effect on bone metastases. Alpha-particle emitters such as radium-223 dichloride have very short penetration of tissue (less than 100 micrometers, or 2 to 10 cell diameters), resulting in minimal damage to surrounding tissue.

After intravenous administration, radium-223 exhibits linear pharmacokinetics and is rapidly cleared from the bloodstream and distributed primarily into bone or excreted into the intestine. Based on calculations from data in 5 patients with castration-resistant prostate cancer, radioactivity to bone approximates 4,262.6 rad/mCi, red marrow and upper and lower large intestine walls each absorb less than 515 rad/mCi of radiation, and other organs absorb less than 27 rad/mCi per dose. Fifteen minutes after administration, 20% of the injected radioactive dose remained in the blood; after 4 hours, 4% remained in the blood (61% in bone, no significant uptake in heart, liver, kidneys, urinary bladder, and spleen); after 24 hours, less than 1% remained in the blood.
Radium-223 dichloride is a radiopharmaceutical isotope that decays and is not metabolized. After correcting for decay, approximately 63% of the administered radioactivity was excreted from the body within 7 days of administration, with 13% (range, 0% to 34%) in fecal matter at 48 hours and 2% (range, 1% to 5%) in urine. The rate of elimination is influenced by intestinal transit rates; it is unknown whether patients with slower transit rates will receive higher intestinal radiation exposure and thus increased gastrointestinal toxicity. Radium-223 dichloride has a physical half-life of 11.4 days.

Radium-223 dichloride is not indicated for use in women. According to the manufacturer, it is unknown whether radium-223 dichloride is excreted in human milk; however, there is potential for serious radiation-related adverse effects in nursing infants. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.