Misoprostol for Cervical Ripening: Informed Consent Is Not Optional
The Responsibility Clause - Should patients be informed that a recommended medication is not FDA approved?
The Guideline and the Gap
In July 2025, ACOG released Clinical Practice Guideline No. 9, recommending the use of misoprostol for cervical ripening and labor induction. Misoprostol (aka ‘Cytotec’) is a medication approved for preventjng and treating stomach ulcers and it is inexpensive, and widely used. In pregnancy, doctors can give it orally of vaginally to soften the cervix and induce labor. Yet it remains FDA-unapproved for obstetric use. The manufacturer’s own labeling explicitly warns against its use for inducing labor, citing risks of uterine rupture, tachysystole (too many contractions), amniotic fluid embolus (AFE), and fetal distress. The official Cytotec insert states that “a major adverse effect of the obstetrical use of Cytotec is uterine tachysystole which may progress to uterine tetany with marked impairment of uteroplacental blood flow, uterine rupture… or amniotic fluid embolism and lead to adverse fetal heart changes.”
Despite these warnings, this ACOG guideline refers to misoprostol as strongly recommended for appropriate patients, mentioning that women “should be counseled on methods available for cervical ripening, as well as the benefits and risks.” This phrasing acknowledges the need for counseling but stops short of requiring true informed consent, especially for a drug used off-label and associated with potentially life-threatening complications.
Only 3 Drugs are Recommended Off-Label
A recent comprehensive review confirms that only four drugs—misoprostol, nifedipine, and corticosteroids—represent the main off-label medications routinely used in obstetrics.
Misoprostol, unapproved by the FDA for labor induction, is recommended by ACOG for cervical ripening and induction of labor.
Nifedipine, also off-label, is widely used as a tocolytic to suppress preterm contractions.
Corticosteroids, though not specifically approved for promoting fetal lung maturity, are universally endorsed to reduce neonatal morbidity and mortality from preterm birth.
Magnesium sulfate, a medication to prevent brain damage in the fetus during preterm pregnancy.
A 2024 narrative review, which examined over 500 studies and distilled 76 key references, concluded that off-label prescribing in obstetrics has evolved “from being an exception to a routine, scientifically validated practice.” Still, it emphasized that this normalization heightens physicians’ ethical and legal duties to ensure detailed informed consent, continuous monitoring, and transparent communication when using these unapproved but evidence-supported medications.
