DENGVAXIA(Dengue Tetravalent Vaccine, Live)Suspension for Subcutaneous Injection(八)
of DENGVAXIA on embryo-fetal andpost-natal development was eva luated in pregnant rabbits and mice.
Rabbits were administered a full human dose [0.5 mL (5 log10 CCID50/animal/occasion)] ofDENGVAXIA by intravenous injection 30 and 10 days before mating and on Days 6, 12 and 27during gestation. No vaccine-related fetal malformation or variations and adverse effects onfemale fertility or pre-weaning development were reported in this study. Pregnant mice wereadministered a single dose of either 5 log10 CCID50 (full human dose ranging from 4.5 log10 to 6.0 log10 CCID50), 6.5 log10 CCID50 (about 3 times the highest human dose) or 8 log10 CCID50(about 100 times the highest human dose) of DENGVAXIA by intravenous injection on Day 6, 9or 12 of gestation. At doses of 6.5 log10 CCID50 or 8 log10 CCID50 of DENGVAXIA, maternaltoxicity was observed which was associated with increased post-implantation loss and at doses of
8 log10 CCID50 with reduced fetal body weight. The significance of this observation for humansis unknown, especially considering the different route of administration (the human route ofadministration is subcutaneous) and dose levels which exceeded the intended human dose.
Therewere no vaccine related fetal malformations or other evidence of teratogenesis noted in this study.
8.2 Lactation
Risk Summary
Human data are not available to assess the impact of DENGVAXIA on milk production, itspresence in breast milk, or its effects on the breastfed child. The developmental and healthbenefits of breastfeeding should be considered along with the mother’s clinical need forDENGVAXIA and any potential adverse effects on the breastfed child from DENGVAXIA orfrom the underlying maternal condition. For preventive vaccines, the underlying condition issusceptibility to disease prevented by the vaccine. A lactation study in which female mice wereadministered a single dose of DENGVAXIA on day 14 of lactation did not show the presence ofDENGVAXIA in breast milk.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Vertical transmission of dengue virus, including potentially through breastmilk, has been reported.
Fetal/neonatal adverse reactions
Vaccine viremia can occur 7 to 14 days after vaccination with a duration of <7 days. [SeePharmacokinetics (12.3).] The potential for transmission of the vaccine virus from mother toinfant through breastmilk is unknown.
Animal Data
A developmental toxicity study in which female mice were administered a single injection of 5log10 CCID50 (full human dose ranging from 4.5 log10 to 6.0 log10 CCID50), 6.5 log10 CCID50 or 8log10 CCID50 of DENGVAXIA by intravenous injection on Day 14 of lactation did not show thepresence of DENGVAXIA in breast milk in mice when measured 24 hours after vaccineadministration.
8.4 Pediatric Use
Safety and effectiveness of DENGVAXIA in children younger than 9 years of age have not been
established.
8.5 Geriatric Use
Safety and effectiveness of DENGVAXIA in adults 65 years of age and older have not been
established.
11 DESCRIPTION
DENGVAXIA (Dengue Tetravalent Vaccine, Live) is a sterile suspension for subcutaneousinjection.
DENGVAXIA is supplied as a vial of lyophilized vaccine antigen, which must bereconstituted at the time of use with 0.6 mL from the accompanying vial of diluent (0.4% sodiumchloride). After reconstitution, DENGVAXIA is a clear, colorless suspension (trace amounts ofwhite to translu |
