Why the Controversy?
The use of drugs for off-label indications is legal, common practice, and not considered experimental if based on sound scientific evidence. Unlike the off-label use of other drugs, the use of misoprostol for labor induction has sparked considerable controversy. Part of the controversy stems from our inability to answer the question of whether misoprostol used in low doses to induce labor in women without prior cesareans, is any less safe than other agents used for the same purpose. We know from approximately 5400 women enrolled in randomized trials of vaginal misoprostol for induction of labor and 9400 women enrolled in randomized trials of other prostaglandins for induction of labor that serious adverse outcomes are extremely rare, and any absolute differences between agents are likely to be small. Nonetheless, when methodologically sound evidence cannot yet, or possibly ever, conclusively answer an important question, we are left with (at least the potential for) controversy.
The use of misoprostol for induction of labor is also controversial for other reasons. First, because medical abortion with mifepristone and misoprostol has the potential to improve access to abortion services, political opponents of abortion may view misoprostol as a threat and a target. In September 2000, mifepristone was approved by the FDA to be used in conjunction with misoprostol for early pregnancy termination, yet misoprostol was not approved for the same purpose. In fact, product labeling formerly included a warning that misoprostol is contraindicated in pregnancy because of its abortifacient properties. That warning was changed in May of 2002 to state that misoprostol is contraindicated for use as an antiulcer drug in pregnant women. However, misoprostol is still not FDA approved for any obstetric or gynecologic indication, and warnings about risks associated with its use for induction of labor remain on the label.
Second, as a labor-inducing agent, misoprostol is usually used in women with full-term healthy fetuses. Although serious adverse outcomes are rare in this population, when they do occur, medico-legal exposure is high. Although misoprostol is not FDA approved for this indication and warnings about possible complications from its use for induction of labor remain on the package insert, other prostaglandin preparations are FDA approved for labor induction.
The main impetus for a pharmaceutical manufacturer to seek FDA approval for a new indication for an already approved drug is increased marketing for the new indication. Little incentive exists for a pharmaceutical company to engage in the expensive process required to add an indication to the label of misoprostol when the legal, financial, and political risks are high and the additional profits from marketing and sales are likely to be low. Despite evidence to support its use, misoprostol is unlikely to gain FDA approval for labor induction because clinicians are already using it without product labeling for obstetrics.
J Midwifery Womens Health. 2003;48(4) © 2003 Elsevier Science, Inc.
Cite this: Induction of Labor: The Misoprostol Controversy - Medscape - Jul 01, 2003.