XOFIGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XOFIGO (XOFIGO).
Radium-223 dichloride is a calcium-mimetic alpha particle-emitting radiopharmaceutical that forms complexes with bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The alpha particles induce double-strand DNA breaks in adjacent cells, resulting in cytotoxic effects.
| Metabolism | Radium-223 is not metabolized and decays to its daughter isotopes. It is primarily eliminated by fecal excretion; 5% is excreted in urine. |
| Excretion | Radium-223 dichloride is primarily excreted via the feces. Approximately 75% of the administered dose is eliminated in feces within 7 days, with a smaller fraction (about 5%) excreted in urine. |
| Half-life | The terminal elimination half-life of radium-223 dichloride is approximately 11 days (range 7–14 days), reflecting the slow turnover of radium in bone. |
| Protein binding | Radium-223 is not metabolized and does not bind to plasma proteins; it exists as a free ion in plasma. |
| Volume of Distribution | Radium-223 has a volume of distribution of approximately 1.6 L/kg, indicating extensive distribution into tissues, particularly bone. |
| Bioavailability | Radium-223 dichloride is administered intravenously, resulting in 100% bioavailability. |
| Onset of Action | Following intravenous injection, radium-223 targets bone metastases and emits alpha particles, leading to DNA damage. Clinical effects on pain and disease progression are typically observed within 2–4 weeks. |
| Duration of Action | The therapeutic effect is sustained over multiple cycles; the recommended dosing schedule is 55 kBq/kg every 4 weeks for 6 doses. Pain relief may last for several months. |
55 kBq (1.49 microcurie) per kg body weight, intravenous injection every 4 weeks.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR 30-89 mL/min). Insufficient data for severe impairment (GFR <30 mL/min); use with caution. No recommended dose in end-stage renal disease. |
| Liver impairment | No formal studies in hepatic impairment; caution as radium-223 is not metabolized by the liver. No Child-Pugh based adjustments established. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required for elderly patients based on clinical studies, but consider overall health status and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XOFIGO (XOFIGO).
| Breastfeeding | It is unknown whether radium Ra 223 is excreted in human milk. Due to the potential for serious adverse reactions (e.g., radiation exposure) in the breastfed infant, breastfeeding is not recommended during treatment and for at least 6 months after the last dose. No M/P ratio is available. |
| Teratogenic Risk | XOFIGO (radium Ra 223 dichloride) is contraindicated in pregnant women. Based on its mechanism of action (alpha particle emission) and animal studies, there is a high risk of fetal harm. Radium-223 emits alpha particles that can cross the placenta and cause severe fetal damage, including teratogenicity and death, at any trimester. No human pregnancy data exist. Effective contraception should be used during treatment and for at least 6 months after the last dose in women of reproductive potential. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pregnancy","Patients with visceral metastases","Patients with contraindications to radiation treatment"]
| Precautions | ["Bone marrow suppression: Monitor blood counts (neutropenia, thrombocytopenia, anemia). Increased risk of fractures and mortality when used in combination with abiraterone and prednisone/prednisolone. Embryo-fetal toxicity. Late radiation toxicity. Increased gastrointestinal adverse reactions in patients with inflammatory bowel disease."] |
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| Fetal Monitoring | Before initiating therapy, exclude pregnancy with a negative serum pregnancy test in women of childbearing potential. During treatment, no specific fetal monitoring is indicated unless accidental exposure occurs. In the event of inadvertent use during pregnancy, immediate radiation safety consultation is required. Routine monitoring includes complete blood counts and renal function as per standard XOFIGO monitoring. |
| Fertility Effects | XOFIGO may impair fertility in both males and females due to radiation-induced gonadal damage. In animal studies, radium-223 caused testicular atrophy and reduced spermatogenesis. In humans, radiation exposure can lead to ovarian failure, azoospermia, and irreversible infertility. Patients should be informed of potential fertility risks and consider sperm or oocyte cryopreservation before treatment. |