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晚期胃癌药品Cyramza（ramucirumab）再次获FDA批准扩展治疗结直肠癌(十一)
al Data
No animal studies have been specifically conducted to eva luate the effect of ramucirumab on reproduction and fetal development. In mice, loss of the VEGFR2 gene resulted in embryofetal death and these fetuses lacked organized blood vessels and blood islands in the yolk sac. In other models, VEGFR2 signaling was associated with development and maintenance of endometrial and placental vascular function, successful blastocyst implantation, maternal and feto-placental vascular differentiation, and development during early pregnancy in rodents and non-human primates. Disruption of VEGF signaling has also been associated with developmental anomalies including poor development of the cranial region, forelimbs, forebrain, heart, and blood vessels.
8.2 Lactation
Risk Summary
There is no information on the presence of ramucirumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential risk for serious adverse reactions in nursing infants from ramucirumab, advise women that breastfeeding is not recommended during treatment with CYRAMZA.
8.3 Females and Males of Reproductive Potential
Contraception
Females
Based on its mechanism of action, CYRAMZA can cause fetal harm [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception while receiving CYRAMZA and for at least 3 months after the last dose of CYRAMZA.
Infertility
Females
Advise females of reproductive potential that based on animal data CYRAMZA may impair fertility [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
The safety and effectiveness of CYRAMZA in pediatric patients have not been established. In animal studies, effects on epiphyseal growth plates were identified. In cynomolgus monkeys, anatomical pathology revealed adverse effects on the epiphyseal growth plate (thickening and osteochondropathy) at all doses tested (5-50 mg/kg). Ramucirumab exposure at the lowest weekly dose tested in the cynomolgus monkey was 0.2 times the exposure in humans at the recommended dose of ramucirumab as a single agent.
8.5 Geriatric Use
Of the 563 CYRAMZA-treated patients in two randomized gastric cancer clinical studies, 36% were 65 and over, while 7% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. [see Clinical Studies (14.1)]
Of the 1253 patients in Study 3, 455 (36%) were 65 and over and 84 (7%) were 75 and over. Of the 627 patients who received CYRAMZA plus docetaxel in Study 3, 237 (38%) were 65 and over, while 45 (7%) were 75 and over [see Clinical Studies (14.2)]. In an exploratory subgroup analysis of Study 3, the hazard ratio for overall survival in patients less than 65 years old was 0.74 (95% CI: 0.62, 0.87) and in patients 65 years or older was 1.10 (95% CI: 0.89, 1.36). [see Clinical Studies (14.2)]
Of the 529 patients who received CYRAMZA plus FOLFIRI in Study 4, 209 (40%) were 65 and over, while 51 (10%) were 75 and over. Overall, no differences in safety or effectiveness were observed between these subjects and younger subjects. [see Clinical Studies (14.3)]
8.6 Renal Impairment
No dose adjustment is recommended for patients with renal impairment based on population pharmacokinetic analysis [see Clinical Pharmacology (12.3 |
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