l factors, includingassay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data with ESPEROCT use in pregnant women to determine whether there is a drug-associated risk. Animalreproduction studies have not been conducted with ESPEROCT. It is unknown whether ESPEROCT can cause fetal harmwhen administered to a pregnant woman or can affect fertility.
In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognizedpregnancies is 2–4% and 15–20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of ESPEROCT in human milk, the effect on the breastfed infant, and theeffects on milk production. The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for ESPEROCT and any potential adverse effects on the breastfed infant from ESPEROCT or from theunderlying maternal condition.
8.4 Pediatric Use
Safety and efficacy were eva luated in 93 previously treated pediatric patients <18 years of age, who received at least onedose of ESPEROCT; all received routine prophylaxis [see Clinical Studies (14)]. Thirty-four (34) of these subjects (36.6%)were 1 to <6 years of age; 34 subjects (36.6%) were 6 to <12 years of age; and 25 subjects (27%) were 12 to <18 years ofage. Pharmacokinetic parameters were eva luated for 27 of these subjects who were treated with ESPEROCT [see Clinical
Pharmacology (12.3)].
No difference in the safety profile of ESPEROCT was observed between previously treated pediatric subjects and adultsubjects. Pharmacokinetic studies in children <12 years of age demonstrated higher clearance, a shorter half-life, and lowerincremental recovery of Factor VIII compared to adults, but the pharmacokinetic parameters are comparable between youngchildren (1–<6 years) and older children (6–<12 years). Because clearance (per kg body weight) is higher in children (<12years), a higher dose and more frequent dosing may be needed in this population [see Clinical Pharmacology (12.3)].
8.5 Geriatric Use
Clinical studies of ESPEROCT did not include sufficient numbers of subjects age 65 years and over to determine whether ornot they respond differently than younger subjects. Other reported clinical experience has not identified differences inresponses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious,usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease and other drug therapy.
11 DESCRIPTION
ESPEROCT is a sterile, preservative-free, non-pyrogenic lyophilized powder for intravenous injection after reconstitutionwith the provided saline diluent. The active ingredient in ESPEROCT is a recombinant analogue of human coagulationFactor VIII (FVIII) conjugated with a 40-kDa polyethylene glycol (PEG) molecule. ESPEROCT is formulated with thefollowing excipients: sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, and calcium chloride.
FVIII activity in ESPEROCT is determined using the chromogenic assay described in the European Pharmacopoeia. Theactivity assignment employs a FVIII reference material t |
