Uses of Misoprostol in Obstetrics and GynecologyRebecca Allen, MD, MPH and Barbara M OBrien, MDDepartment of Obstetrics and Gynecology, Women and Infants Hospital and Warren Alpert Medical School of Brown University, Providence, RIAbstractMisoprostol is a synthetic prostaglandin E1 analogue that is used off-label for a variety of indications in the practice of obstetrics and gynecology, including medication abortion, medical management of miscarriage, induction of labor, cervical ripening before surgical procedures, and the treatment of postpartum hemorrhage. Due to its wide-ranging applications in reproductive health, misoprostol is on the World Health Organization Model List of Essential Medicines. This article briefly reviews the varied uses of misoprostol in obstetrics and gynecology.Key words: Misoprostol, Induced abortion, Induction of labor, Postpartum hemorrhage, Cervical ripening, HysteroscopyMisoprostol is a synthetic prostaglandin E1 analogue marketed as an oral preparation used to prevent and treat gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, misoprostol is used off-label for a variety of indications in the practice of obstetrics and gynecology, including medication abortion, medical management of miscarriage, induction of labor, cervical ripening before surgical procedures, and the treatment of postpartum hemorrhage. Misoprostols effects are dose dependent and include cervical softening and dilation, uterine contractions, nausea, vomiting, diarrhea, fever, and chills. Although misoprostol is not approved by the US Food and Drug Administration (FDA) for these indications, in 2002, pregnancy was removed from the label as an absolute contraindication to misoprostol use. Misoprostols advantages over other synthetic prostaglandin analogues are its low cost, long shelf life, lack of need for refrigeration, and worldwide availability (Figure 1).PharmacokineticsRoutes of misoprostol administration include oral, vaginal, sublingual, buccal, or rectal. Pharmacokinetics studies (Figure 2) comparing oral and vaginal administration have shown that vaginal misoprostol is associated with slower absorption, lower peak plasma levels, and slower clearance, similar to an extended-release preparation. Vaginal misoprostol is also associated with a greater overall exposure to the drug (area under the curve AUC) and greater effects on the cervix and uterus. There is, however, a wide variation in the absorption of misoprostol through the vaginal epithelium among different women. There is no clinically significant difference between vaginal misoprostol that is administered dry and vaginal misoprostol moistened with water, saline, or acetic acid.The rectal route of administration shows a similar pattern to vaginal administration, but has a lower AUC, including a significantly lower maximum peak concentration. The sublingual route of administration has an AUC similar to vaginal administration, but more rapid absorption and higher peak levels than either vaginal or oral administration (Figure 2). This translates into higher rates of gastrointestinal side effects. Nevertheless, the sublingual route also causes uterine contractions at a rate equivalent to vaginal administration and has less variation in absorption. The buccal route of administration shows a lower AUC, a lower peak concentration, and fewer side effects than sublingual administration. The buccal route has a pattern of absorption similar to the vaginal route, but produces lower serum levels overall. Nonetheless, the buccal and vaginal routes of administration have similar effects on uterine tone and activity. The buccal route of administration is also thought to be the least variable in terms of drug exposure and peak levels. The administration of NSAIDs for pain relief does not alter the efficacy of misoprostol. There are no known drug interactions with misoprostol.TeratogenicityMisoprostol is considered a teratogen. Congenital defects following prenatal exposure in early pregnancy to misoprostol include skull defects, bladder exstrophy, arthrogryposis, cranial nerve palsies, facial malformations, terminal transverse limb defects, and Moebius sequence.This constellation of congenital malformations is thought to be due to a vascular disruption secondary to uterine contractions caused by misoprostol. The incidence of these abnormalities does not appear to be high when population registries have been studied, especially given that exposure to misoprostol is quite common among some populations of patients. The absolute risk of congenital malformations after prenatal exposure to misoprostol is estimated to be approximately 1%.Pharmacokinetic studies reveal that misoprostol is excreted into breast milk with drug levels that rise and fall very quickly. Levels become undetectable within 5 hours of maternal ingestion. However, breastfeeding women should be advised that misoprostol ma