odies toromosozumab-aqqg, 4.7% had antibodies that were classified as neutralizing. Development of antibodiesto romosozumab-aqqg was associated with lower serum romosozumab-aqqg concentrations [see ClinicalPharmacology (12.3)].
Antibodies to romosozumab-aqqg were generally not associated with changes inthe efficacy or safety of EVENITY.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
EVENITY is not indicated for use in women of reproductive potential. In animal reproduction studies,weekly administration of romosozumab-aqqg to pregnant rats during the period of organogenesis atexposures greater than 32 times the clinical exposure produced skeletal abnormalities in the offspring.
Administration of romosozumab-aqqg to rats prior to mating and through to the end of lactation producedminimal to slight decreases in femoral bone mineral density and/or cortical circumferences in theoffspring at 1.5 to 56 times the expected exposure in humans [see Data].
Data
Animal Data
Reproductive and developmental effects of romosozumab-aqqg were assessed in the rat in a preliminaryand definitive embryo-fetal development study, a combined fertility and embryo-development study, anda pre- and postnatal development study.
Skeletal malformations including syndactyly and polydactyly occurred in 1 out of 75 litters across all ratreproductive toxicity studies, in the litter of a dam given weekly subcutaneous romosozumab-aqqg dosesof 300 mg/kg (equivalent to at least 32 times the clinical exposure observed in humans following amonthly subcutaneous dose of 210 mg, based on area under the concentration-time curve [AUC]comparison).
In the offspring of female rats given weekly romosozumab-aqqg doses from 6 weeks before cohabitationthrough mating and lactation, femoral periosteal and endocortical circumferences were slightly decreasedat 10, 60, and 300 mg/kg (equivalent to 1.5, 19, and 56 times the clinical exposure following a monthlysubcutaneous dose of 210 mg, based on AUC comparison). Cortical thickness was increased at 300 mg/kg(equivalent to 56 times expected clinical exposure). Femoral metaphyseal bone mineral density wasslightly decreased at 60 and 300 mg/kg (equivalent to 19 and 56 times expected clinical exposure).
8.2 Lactation
Risk Summary
EVENITY is not indicated for use in women of reproductive potential. In animal studies where pregnantrats were given weekly doses of romosozumab-aqqg from 6 weeks before cohabitation through matingand lactation at 10, 60, or 300 mg/kg (equivalent to 1.5, 19 or 56 times the clinical exposure following amonthly subcutaneous dose of 210 mg, based on AUC comparison), romosozumab-aqqg wasdose-dependently present in the serum of offspring on postnatal day 21 at 0.01 to 2.4 times maternal
exposure due to gestational and/or lactational exposure.
8.4 Pediatric Use
Safety and effectiveness of EVENITY have not been established in pediatric patients.
8.5 Geriatric Use
Of the 6544 postmenopausal women with osteoporosis in the clinical studies of EVENITY, 5234 (80%)were age 65 years and over and 2390 (37%) were age 75 years and over. No overall differences in safetyor efficacy were observed between these subjects and younger subjects, and other reported clinicalexperience has not identified differences in response between the elderly and younger patients, but greatersensitivity of some older individuals cannot be ruled out.
8.7 Renal Impairment
No d |
