nt becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with Xofigo.
8.3 Nursing Mothers
Xofigo is not indicated for use in women. It is not known whether radium-223 dichloride is excreted in human milk. Because many drugs are excreted in human milk, and because of potential for serious adverse reactions in nursing infants from Xofigo, a decision should be made whether to discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and efficacy of Xofigo in pediatric patients have not been established.
In single- and repeat-dose toxicity studies in rats, findings in the bones (depletion of osteocytes, osteoblasts, osteoclasts, fibro-osseous lesions, disruption/disorganization of the physis/growth line) and teeth (missing, irregular growth, fibro-osseous lesions in bone socket) correlated with a reduction of osteogenesis that occurred at clinically relevant doses beginning in the range of 20 – 80 kBq (0.541 - 2.16 microcurie) per kg body weight.
8.5 Geriatric Use
Of the 600 patients treated with Xofigo in the randomized trial, 75% were 65 years of age and over and while 33% were 75 years of age and over. No dosage adjustment is considered necessary in elderly patients. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
8.6 Patients with Hepatic Impairment
No dedicated hepatic impairment trial for Xofigo has been conducted. Since radium-223 is neither metabolized by the liver nor eliminated via the bile, hepatic impairment is unlikely to affect the pharmacokinetics of radium-223 dichloride [see Clinical Pharmacology (12.3)]. Based on subgroup analyses in the randomized clinical trial, dose adjustment is not needed in patients with mild hepatic impairment. No dose adjustments can be recommended for patients with moderate or severe hepatic impairment due to lack of clinical data.
8.7 Patients with Renal Impairment
No dedicated renal impairment trial for Xofigo has been conducted. Based on subgroup analyses in the randomized clinical trial, dose adjustment is not needed in patients with existing mild (creatinine clearance [CrCl] 60 to 89 mL/min) or moderate (CrCl 30 to 59 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CrCl less than 30 mL/min) due to limited data available (n = 2) [see Clinical Pharmacology (12.3)].
8.8 Males of Reproductive Potential
Contraception
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 with Xofigo.
Infertility
There are no data on the effects of Xofigo on human fertility. There is a potential risk that radiation by Xofigo could impair human fertility [see Nonclinical Toxicology (13.1)].
10 OVERDOSAGE
There have been no reports of inadvertent overdosing of Xofigo during clinical studies.
There is no spec |
