Dosing and uses of Xofigo (radium-223 dichloride)
Adult dosage forms and strengths
IV solution
- 1100 kBq/mL (30 microcurie/mL)
- Available as 6mL/single-use vial
Prostate Cancer
Indicated for treatment of men with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease
55 kBq (1.49 microcurie) per kg IV infused over 1 minute; repeat q4weeks for 6 cycles totaL
Dosage calculation must be based on decay correction factor of radium-223
Dose calculation
- Volume to be administered should be calculated using the:
- -Patient’s body weight (kg)
- -Dosage level 55 kBq/kg body weight or 1.49 microcurie/kg body weight
- -Radioactivity concentration of the product (1,100 kBq/mL; 30 microcurie/mL) at the reference date
- -Decay correction factor to correct for physical decay of radium-223
- Example: (Body wt in kg x 55 kBq/kg body weight) ÷ (Decay factor x 1,100 kBq/mL) or (Body wt in kg x 1.49 microcurie body weight) ÷ (Decay factor x 30 microcurie/mL)
- Decay correction factor table listed in prescribing information and is based on the vial’s reference date
Dosing Considerations
Safety beyond 6 treatment cycles not established
Pediatric dosage forms and strengths
Safety and efficacy not established
Xofigo (radium-223 dichloride) adverse (side) effects
>10%
Percentages includes all toxicity grades (1-4)
Anemia (93%)
Lymphocytopenia (72%)
Leukopenia (35%)
Thrombocytopenia (31%)
Nausea (36%)
Diarrhea (25%)
Vomiting (19%)
Neutropenia (18%)
Peripheral edema (13%)
1-10%
Percentages includes all toxicity grades (1-4)
Renal failure and impairment (3%)
Dehydration (3%)
Pancytopenia (2%)
Erythema, pain, and edema at injection site (1%)
Warnings
Contraindications
Pregnancy; radium-223 can cause fetal harm when administered to a pregnant woman based on its mechanism of action; not indicated for use in women and is contraindicated in women who are or may become pregnant
Cautions
May cause myelosuppression and bone marrow failure; perform hematologic evaluation at baseline and prior to every dose; discontinue if life-threatening complications occur despite supportive care for bone marrow failure
Safety and efficacy of concomitant chemotherapy have not been established; outside of a clinical trial, concomitant use with chemotherapy is not recommended due to the potential for additive myelosuppression
Because of potential effects on spermatogenesis associated with radiation, advise men who are sexually active to use condoms and their female partners of reproductive potential to use a highly effective contraceptive method during and for 6 months after completing treatment
Pregnancy and lactation
Pregnancy category: X
Lactation: Not indicated for women; unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Xofigo (radium-223 dichloride)
Mechanism of action
Alpha particle-emitting radiopharmaceutical; contains the heavy metal radium, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases; this causes double-strand DNA breaks that are lethal to the prostate cancer cell at the site of increased bone turnover induced by the cancer
Absorption
Peak blood levels were linear in terms of dose proportionality and time independence in the dose range investigated
Distribution
After IV injection, rapidly cleared from the blood and distributed primarily into bone or is excreted into intestine
No significant uptake was seen in other organs such as heart, liver, kidneys, urinary bladder, and spleen at 4 hours post-injection
Detected in blood post-injection
- 15 minutes: ~20% remains in blood
- 4 hr: ~4% remains in blood
- 24 hr: <1% remains in blood
Detected in bone/intestine post-injection
- 10 minutes: Radioactivity was observed in bone and in intestine
- 4 hr: Percentage of the radioactive dose present in bone and intestine was approximately 61% and 49%, respectively
Metabolism
Isotope that decays and is not metabolized
Elimination
~63% excreted from body within 7 days after injection (after correcting for decay)
Fecal excretion is the major elimination route; at 48 hr after injection, the cumulative fecal excretion was 13% (range 0 -34%), and the cumulative urine excretion was 2% (range 1 -5%)
Administration
IV Administration
Follow procedures for proper handling and disposal of radioactive pharmaceuticals
Inspect visually for particulate matter and discoloration before administering
Ready-to-use IV solution; do not dilute or mix with any solutions
Slow IV injection over 1 minute
Flush IV line/cannula with 0.9% NaCl before and after injection
Storage
Store at room temperature, below 40°C (104°F)
Store in original container or equivalent radiation shielding
