Radium 223 Dichloride (Xofigo)

CHEMOCARE

CHEMOCARE

WARNINGS AND PRECAUTIONS

Bone Marrow Suppression: Measure blood counts prior to treatment initiation and before every dose of Xofigo. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after treatment. Monitor patients with compromised bone marrow reserve closely. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care measures

These are less common (occurring in 1-5%) side effects for patients receiving Radium 223 Dichloride:

Dehydration Injection site reactions (redness, pain, swelling) Kidney failure / impairment

FDA LABEL

FDA LABEL

Bone Marrow Suppression

In the randomized trial, 2% of patients on the Xofigo arm experienced bone marrow failure or ongoing pancytopenia compared to no patients treated with placebo. There were two deaths due to bone marrow failure and for 7 of 13 patients treated with Xofigo, bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients on the Xofigo arm and 2% on the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) were similar for patients treated with Xofigo and placebo. Myelosuppression; notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia; has been reported in patients treated with Xofigo. In the randomized trial, complete blood counts (CBCs) were obtained every 4 weeks prior to each dose and the nadir CBCs and times of recovery were not well characterized. In a separate single-dose phase 1 study of Xofigo, neutrophil and platelet count nadirs occurred 2 to 3 weeks after Xofigo administration at doses that were up to 1 to 5 times the recommended dose, and most patients recovered approximately 6 to 8 weeks after administration [see Adverse Reactions (6)]. Hematologic evaluation of patients must be performed at baseline and prior to every dose of Xofigo. Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥ 1.5 x 109 /L, the platelet count ≥ 100 x 109 /L and hemoglobin ≥ 10 g/dL. Before subsequent administrations of Xofigo, the ANC should be ≥ 1 x 109 /L and the platelet count ≥ 50 x 109 /L. If there is no recovery to these values within 6 to 8 weeks after the last administration of Xofigo, despite receiving supportive care, further treatment with Xofigo should be discontinued. Patients with evidence of compromised bone marrow reserve should be monitored closely and provided with supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure. The safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use with chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued.

The following side effects are common (occurring in greater than 10%) for patients taking Radium 223 Dichloride

Nausea Vomiting Diarrhea Swelling of the lower legs and hands [peripheral edema] Low blood counts. Your white and red blood cells and platelet counts may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding.

How Radium 223 Dichloride Works

Radium-223 dichloride is a type of radiopharmaceutical. Radiopharmaceuticals are radioactive drugs. Radiopharmaceuticals are used in the field of nuclear medicine as radioactive tracers in the diagnosis and treatment of many diseases. A radioactive tracer is a chemical compound with an attached radioactive isotope [a variant of a chemical element] that can be introduced into and tracked within the body. Through a complex process, these radioactive isotopes undergo radioactive decay, resulting in the emission of particles such as alpha or beta particles. Radioactive isotopes are used primarily either for their chemical properties or as a source of radiation. Radionuclides of similar elements can serve as radioactive tracers because they are similar chemically to the non-radioactive elements. There are some radionuclides that are bone seeking radioisotopes and those radionuclides exhibit chemical behavior similar to calcium, allowing them to be absorbed in areas where cancer is present in the bone. Once in the bone, the radioisotope emits beta or alpha particles, which kill the nearby cancer cells. *Radium-223 dichloride is an alpha-particle emitting radio isotope. The drug mimics calcium and forms complexes with the bone mineral at sites of bone metastases. It then emits alpha particles, causing the destruction of DNA in nearby cells, resulting in cancer cell death in the bone.*

How Radium 223 Dichloride Is Given

Radium-223 dichloride is given through a vein (intravenously, IV), as a slow [intravenous] injection, over about 1 minute There is no pill form of radium-223 dichloride. It is given in a clinic or facility where healthcare providers or technicians have been trained to give radiation therapy. It is given once every 4 weeks for a maximum of 6 doses.

Mechanism of Action

The active moiety of Xofigo 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 (see Table 2). 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

DOSAGE AND ADMINISTRATION

The dose regimen of Xofigo is 50 kBq (1.35 microcurie) per kg body weight, given at 4 week intervals for 6 injections

What Radium 223 Dichloride Is Used For

The treatment of patients with prostate cancer that is resistant to medical or surgical treatments that lower testosterone and has spread to bones with symptoms, but not to other parts of the body

INDICATIONS AND USAGE

Xofigo is an alpha particle-emitting radioactive therapeutic agent indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease

The most common hematologic laboratory abnormalities (≥ 10%) were

anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia

The most common adverse drug reactions (≥ 10%) in patients receiving Xofigo were

nausea, diarrhea, vomiting, and peripheral edema

Xofigo is contraindicated in

pregnancy

Radium-223 dichloride is not currently indicated for use in ____________

women -However, if radium-223 dichloride is given to a woman, getting pregnant should be avoided and the woman should not breast feed. Pregnancy category X (radium-223 dichloride may cause fetal harm when given to a pregnant woman). This drug must not be given to a pregnant woman or a woman who intends to become pregnant. If a woman becomes pregnant while taking radium-223 dichloride, the medication must be stopped immediately and the woman given appropriate counseling).