Pregnancy category X: See boxed CONTRAINDICATIONS AND WARNINGS regarding misoprostol. 

Non-teratogenic effects

See boxed CONTRAINDICATIONS AND WARNINGS. Misoprostol may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman. Misoprostol may produce uterine contractions, uterine bleeding, and expulsion of the products of conception. Misoprostol has been used to ripen the cervix, to induce labor, and to treat postpartum hemorrhage, outside of its approved indication. A major adverse effect of these uses is hyperstimulation of the uterus. Uterine rupture, amniotic fluid embolism, severe genital bleeding, shock, fetal bradycardia, and fetal and material death have been reported. Higher doses of misoprostol, including the 100 mcg tablet, may increase the risk of complications from uterine hyperstimulation. Diclofenac sodium and misoprostol delayed-release tablets, which contain 200 mcg of misoprostol, are likely to have a greater risk of uterine hyperstimulation than the 100 mcg tablet of misoprostol. Abortions caused by misoprostol may be incomplete. If a woman is or becomes pregnant while taking this drug, the drug should be discontinued and the patient apprised of the potential hazard to the fetus. 

Cases of amniotic fluid embolism, which resulted in maternal and fetal death, have been reported with use of misoprostol during pregnancy. Severe vaginal bleeding, retained placenta, shock, fetal bradycardia, and pelvic pain have also been reported. These women were administered misoprostol vaginally and/or orally over a range of doses. 

Additionally, because of the known effects of nonsteroidal anti-inflammatory drugs including the diclofenac sodium component of diclofenac sodium and misoprostol delayed-release tablets, on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided. 

Teratogenic effects

See boxed CONTRAINDICATIONS AND WARNINGS. Congenital anomalies sometimes associated with fetal death have been reported subsequent to the unsuccessful use of misoprostol as an abortifacient, but the drug's teratogenic mechanism has not been demonstrated. Several reports in the literature associate the use of misoprostol during the first trimester of pregnancy with skull defects, cranial nerve palsies, facial malformations, and limb defects. 

An oral teratology study has been performed in pregnant rabbits at dose combinations (250:1 ratio) up to 10 mg/kg/day diclofenac sodium (120 mg/ m2/day, 0.8 times the recommended maximum human dose based on body surface area) and 0.04 mg/kg/day misoprostol (0.48 mg/ m2/day, 0.8 times the recommended maximum human dose based on body surface area) and has revealed no evidence of teratogenic potential for diclofenac sodium and misoprostol delayed-release tablets. 

Oral teratology studies have been performed in pregnant rats at doses up to 1.6 mg/kg/day (9.6 mg/ m2/day, 16 times the recommended maximum human dose based on body surface area) and pregnant rabbits at doses up to 1.0 mg/kg/day (12 mg/ m2/day, 20 times the recommended maximum human dose based on body surface area) and have revealed no evidence of teratogenic potential for misoprostol. 

Oral teratology studies have been performed in pregnant mice at doses up to 20 mg/kg/day (60 mg/ m2/day, 0.4 times the recommended maximum human dose based on body surface area), pregnant rats at doses up to 10 mg/kg/day (60 mg/ m2/day, 0.4 times the recommended maximum human dose based on body surface area) and pregnant rabbits at doses up to 10 mg/kg/day (120 mg/ m2/day, 0.8 times the recommended maximum human dose based on body surface area) and have revealed no evidence of teratogenic potential for diclofenac sodium. 

However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women.