Xolair Use In Pregnancy & Lactation

Pregnancy: Risk Summary: There are no well-controlled clinical studies of Xolair in pregnant women. A prospective pregnancy registry study (EXPECT) in 250 pregnant women with asthma exposed to Xolair showed the prevalence of major congenital anomalies was similar (8.1% vs 8.9%) between EXPECT and disease matched (moderate and severe asthma) patients. This study cannot definitively establish the absence of any risk, however, because of methodological limitations; including a nonrandomized study design and potential differences between the registry population and the comparator group (see Data: Human Data as follows). IgG molecules are known to cross the placental barrier. In animal reproduction studies, no evidence of fetal harm was observed in cynomolgus monkeys with subcutaneous doses of omalizumab up to approximately 8 times the maximum recommended human dose (MRHD) of 8.75 mg/kg/week on mg/kg basis (see Data: Animal Data as follows).
Clinical considerations: Disease-associated maternal and/or embryo/fetal risk: In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.
Data: Human data: A prospective pregnancy registry study (EXPECT) conducted in the US from 2006 to 2018, included 250 pregnant women with asthma treated with Xolair. 246 of the women were exposed to Xolair in the first trimester of pregnancy and 78.4% (196/250) of the women were exposed to Xolair at least once during all 3 trimesters of pregnancy with an overall median exposure duration of 8.7 months. The EXPECT findings for relevant mother and infant subgroups were compared to age-adjusted frequencies in a disease matched external cohort of 1,153 pregnant women with asthma (without exposure to Xolair) identified from healthcare databases of residents in the Canadian province of Quebec, and termed the Quebec External Comparator Cohort (QECC).
Among EXPECT infants used for comparison to QECC (n=223), the prevalence of major congenital anomalies (8.1%) was similar to that for QECC infants (8.9%). Among EXPECT pregnancies used for comparison to QECC (n=230), 99.1% led to live births, similar to 99.3% for QECC pregnancies.
A sub-study in EXPECT examined platelet levels in 51 infants born to Xolair exposed women, all of them were in the normal range.
Animal data: Reproduction studies in cynomolgus monkeys have been conducted with omalizumab. Subcutaneous doses up to 75 mg/kg per week (at least 8-fold the MRHD of 8.75 mg/kg/week over a 4-week period) of omalizumab did not elicit maternal toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and did not elicit adverse effects on fetal or neonatal growth when administered throughout late gestation, delivery and nursing.
Doses of omalizumab in excess of the clinical dose have been associated with age-dependent decreases in blood platelets in non-human primates, with a greater relative sensitivity in juvenile animals. In a reproduction study in cynomolgus monkeys, there was no clinical evidence of thrombocytopenia (e.g., purpura) in neonatal monkeys from mothers treated with up to 75 mg/kg/week of omalizumab; however, platelet counts were not measured in these offspring.
Lactation: Risk Summary: While omalizumab presence in human milk after administration of Xolair has not been studied, IgGs are present in human milk and therefore it is expected that omalizumab will be present in human milk. The frequency of infant infections identified in EXPECT was evaluated as an indirect measure of immune system development after exposure during pregnancy or through breast-feeding. The majority of infants in the primary analytic population (77.5%, 186/240) were breast-fed. Serious adverse events (SAEs) categorized as "infections and infestations" were observed in 11.4% (5/44) of infants who were not breast-fed, 10.4% (16/154) of infants who were exposed to Xolair through breast-feeding, and 12.5% (4/32) of infants who were breast-fed without exposure to Xolair through breast-feeding. The study has methodological limitations, including a nonrandomized study design.
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for Xolair and any potential adverse effects on the breast-fed child from omalizumab or from the underlying maternal condition.
Animal Data: The presence of omalizumab in milk was evaluated in female cynomolgus monkeys receiving subcutaneous doses of 75 mg/kg/week. Neonatal serum levels of omalizumab after in utero exposure and 28 days of nursing were between 11% and 94% of the maternal serum level. Milk levels of omalizumab were 0.15% of the maternal serum concentration.
Females and males of reproductive potential: There are no special recommendations for women of child-bearing potential.
Infertility: There are no human fertility data for omalizumab. In specifically-designed non-clinical fertility studies in adult cynomolgus monkeys, including mating studies, no impairment of male or female fertility was observed following repeated subcutaneous dosing with omalizumab at dose levels up to 75 mg/kg/week.