Abrysvo Use In Pregnancy & Lactation

Pregnancy: Risk Summary: All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively, and the estimated background risk of fetal deaths after 20 weeks is 0.6%.
Study 1 enrolled 7,386 pregnant individuals who were randomized 1:1 and received ABRYSVO or placebo (0.5 mL dose, containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description]) revealed no evidence for vaccine-associated increase in the risk of congenital anomalies or fetal deaths. Study 2 evaluated 115 pregnant individuals who received ABRYSVO and 117 who received placebo. A numerical imbalance in preterm births in ABRYSVO recipients was observed compared to placebo recipients in these two clinical studies. Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO [see Potential Risk of Preterm Birth under Precautions, Clinical Trials Experience under Adverse Reactions, Clinical Considerations as follows, Data as follows and Pharmacology: Pharmacodynamics: Clinical Studies: Study in Pregnant Individuals For Efficacy in Their Infants from Birth Through 6 Months of Age under Actions].
A developmental toxicity study was performed in female rabbits administered a vaccine formulation containing two times the antigen content of a single human dose of ABRYSVO prior to and during gestation. The study showed no evidence of harm to the fetus or to postnatal survival, growth, or development (see Animal Data as follows).
Clinical Considerations: Maternal Adverse Reactions: In Study 1, 3,698 pregnant individuals received ABRYSVO and 3,687 received placebo. Local and systemic adverse reactions occurred with greater frequency in the ABRYSVO group. Serious adverse reactions observed in pregnant individuals at a higher rate in the ABRYSVO group compared to the placebo group included pre-eclampsia (1.8% versus 1.4%) and gestational hypertension (1.2% versus 1.1%) [see Clinical Trials Experience under Adverse Reactions].
ABRYSVO has not been studied in pregnant individuals less than 24 weeks gestational age, and those at increased risk for preterm birth.
Fetal/Neonatal Adverse Reactions: The infant safety population included 3,659 and 3,646 infants born to individuals in the ABRYSVO or placebo group, respectively. There were 10 (0.3%) fetal deaths in the ABRYSVO group and 9 (0.2%) in the placebo group. Among the infants born to individuals in the ABRYSVO group and in the placebo group, 207 (5.7%) and 172 (4.7%), respectively, were born preterm [see Potential Risk of Preterm Birth under Precautions, Clinical Trials Experience under Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies: Study in Pregnant Individuals For Efficacy in Their Infants from Birth Through 6 Months of Age under Actions]. Low birth weight was observed in 5.1% of participants in the ABRYSVO group versus 4.3% in the placebo group, and neonatal jaundice was observed in 7.3% in the ABRYSVO group versus 6.9% in the placebo group [see Clinical Trials Experience under Adverse Reactions]. For mortality in the neonatal period among infants born to pregnant individuals in Study 1, there were 3 deaths in the ABRYSVO group and 5 in the placebo group, and for overall mortality including after the neonatal period there were 8 deaths in the ABRYSVO group and 14 in the placebo group. Congenital abnormalities were reported in 5.6% in the ABRYSVO group and 6.7% in the placebo group.
Available data are insufficient to establish or exclude a causal relationship between preterm birth and ABRYSVO. To avoid the potential risk of preterm birth with use of ABRYSVO before 32 weeks of gestation, administer ABRYSVO as indicated in pregnant individuals at 32 through 36 weeks gestational age.
Data: Human Data: In Study 1, 3,698 pregnant individuals received ABRYSVO and 3,687 received placebo at 24 through 36 weeks' gestation. The infant safety population included 3,659 and 3,646 infants born to individuals in the ABRYSVO or placebo group, respectively. Among the infants born to individuals in the ABRYSVO group and in the placebo group, 207 (5.7%) and 172 (4.7%), respectively, had adverse events of preterm birth and 205 (5.6%) and 245 (6.7%), respectively, had reported congenital malformations or anomalies. There were 10 (0.3%) fetal deaths in the ABRYSVO group and 9 (0.2%) in the placebo group.
Animal Data: A pre- and post-natal developmental toxicity study with an embryo-fetal developmental toxicity phase was performed in female New Zealand White rabbits. Rabbits were administered 4 doses by intramuscular injection: at 3 weeks and at 1 week prior to mating, and on gestation days 10 and 24. On each occasion, rabbits received 0.5 mL of a vaccine formulation containing twice the antigen content of F glycoproteins of RSV A and RSV B (120 mcg RSV preF A and 120 mcg RSV preF B), stabilized in prefusion conformation as contained in a single human dose of ABRYSVO [see Description]. No adverse effects on mating, female fertility, or on embryo/fetal or post-natal survival, growth, or development were observed. There were no vaccine-related fetal malformations or variations.
Lactation: Risk Summary: It is not known whether ABRYSVO is excreted in human milk. Data are not available to assess the effects of ABRYSVO on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ABRYSVO and any potential adverse effects on the breastfed child from ABRYSVO or from the underlying maternal condition. For preventative vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.