Fertility: Based on the mechanism of action, the use of NSAIDs, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, including celecoxib, should be considered.
Pregnancy: Teratogenic effects: Pregnancy Category C. Celecoxib was not teratogenic in rabbits up to an oral dose of 60 mg/kg/day (equal to human exposure at 200 mg BID as measured by AUC0-24); however, at oral doses ≥150 mg/kg/day (approximately 2-fold human exposure at 200 mg BID as measured by AUC0-24), caused an increased incidence of ventricular septal defects, a rare event, and fetal alterations, such as ribs fused, sternebrae fused and sternebrae misshapen, was observed. A dose-dependent increase in diaphragmatic hernias was observed in one of two rat studies at oral doses ≥30 mg/kg/day (approximately 6-fold human exposure based on the AUC0-24 at 200 mg BID). There are no studies in pregnant women. CELEBREX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Non-teratogenic effects: Celecoxib produced pre-implantation and post-implantation losses and reduced embryo/fetal survival in rats at oral dosages ≥50 mg/kg/day (approximately 6-fold human exposure based on the AUC0-24 at 200 mg BID). These changes are expected with inhibition of prostaglandin synthesis and are not the result of permanent alteration of female reproductive function, nor are they expected at clinical exposures. No studies have been conducted to evaluate the effect of celecoxib on the closure of the ductus arteriosus in humans. Therefore, use of CELEBREX during the third trimester of pregnancy should be avoided.
If used during second or third trimester of pregnancy, NSAIDs may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible. Pregnant women on celecoxib should be closely monitored for amniotic fluid volume.
Labor and delivery: Celecoxib produced no evidence of delayed labor or parturition at oral doses up to 100 mg/kg in rats (approximately 7-fold human exposure as measured by the AUC0-24 at 200 mg BID). The effects of CELEBREX on labor and delivery in pregnant women are unknown.
Inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss.
Nursing mothers: Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. It is not known whether this drug is excreted in human milk. Administration of celecoxib to lactating women has shown very low transfer of celecoxib into breast milk. Because of the potential for serious adverse reactions in nursing infants from CELEBREX, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.