Respiratory Drug (Monoclonal Antibody)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
The limited animal data suggest that the risk of human embryo–fetal harm is low. The rate of spontaneous abortions (SABs) (14%) in women who conceived while under treatment with omalizumab is within the normal background rate for clinically recognized pregnancies. However, the minimal information regarding the other outcomes of the early pregnancy exposures prevents a better assessment of the risk. Other immunoglobulins have been used in pregnancy without causing embryo–fetal harm (see Immune Globulin Intramuscular and Intravenous). Therefore, if indicated, omalizumab should not be withheld because of pregnancy. If a woman has received omalizumab within 8 weeks prior to conception or during pregnancy, health care professionals or patients are encouraged to call 1-866-496-5247 for information about enrollment in the Xolair Pregnancy Registry (EXPECT).
FETAL RISK SUMMARY
Omalizumab is a recombinant DNA-derived humanized immunoglobulin (IgG1k) monoclonal antibody that is administered SC for patients with moderate to severe persistent asthma. Omalizumab selectively binds to human IgE. Patients should have had a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms inadequately controlled by inhaled corticosteroids. Because of its slow absorption, it takes an average of 7–8 days to reach peak serum concentrations. The serum elimination half-life averaged 26 days (1).
Reproduction studies have been conducted in cynomolgus monkeys. At SC doses up to 12 times the maximum human dose based on body weight (MHD) throughout organogenesis, no evidence of maternal toxicity, embryotoxicity, or teratogenicity was observed. The same dose administered throughout late gestation, delivery, and nursing did not cause adverse effects on fetal or neonatal growth. In fertility studies with monkeys, no effect was observed on male or female reproductive capability, including implantation in females, with weekly SC doses 2–5 times the human exposure based on AUC over the range of adult clinical doses (1).
The transplacental passage of omalizumab in humans has not been studied. Although the molecular weight (about 149,000) is high, immune globulin G is known to cross the human placenta and, combined with the long elimination half-life, exposure of the human embryo or fetus should be expected.
No published reports describing the use of omalizumab in human pregnancy have been located. In its safety data, the manufacturer reported 29 pregnancies exposed to omalizumab during clinical trials, but in each case, the drug was discontinued when pregnancy was diagnosed (2). In the completed studies, the outcomes of 17 pregnancies were 3 SABs, 3 elective abortions, and 11 normal deliveries. Of the12 pregnancies in ongoing studies, 1 ended in a SAB. The outcomes of the remaining 11 were normal deliveries or awaiting delivery (number of each not specified). The 4 SABs occurred within 3 months of the last menstrual period. In one case, the woman had a prior history of a SAB. No information (e.g., sex, weight, anomalies, or abnormalities) on the newborn infants was provided (2).
BREASTFEEDING SUMMARY
No reports describing the use of omalizumab during human lactation have been located. If the drug is excreted into milk, the effect of this exposure on a nursing infant is unknown.
References
1.Product information. Xolair. Genentech, 2005.
2.BLA STN 103976/0. Review of Clinical Safety Data. Omalizumab for allergic asthma. Food and Drug Administration—Center for Drug Evaluation and Research website. Available at http://www.fda.gov/cder/biologics/review/omalgen062003r1.pdf. Accessed January 2005.