Preterm labor and delivery is a major determinant of neonatal morbidity and mortality; in the United States, the rate of preterm birth is 12%. A variety of diagnostic and prophylactic measures have been investigated, including home uterine activity monitoring, subcutaneous terbutaline tocolytic therapy, and routine culture and antibiotic treatment of subclinical bacterial vaginosus. To date, none of these have made a significant demonstrable impact on the incidence of preterm delivery. In the past, intramuscular injections of 17 alpha-hydroxyprogesterone (i.e., Delalutin) were used routinely to prevent premature labor. However, the drug was shown to have teratogenic properties (causing abnormal prenatal development), and the U.S. Food and Drug Administration (FDA) labeled the drug as Category D (i.e., studies have demonstrated fetal risk, but use of the drug may outweigh the potential risk). Delalutin was pulled from the market by its manufacturer and is no longer available. Most recently, there has been renewed research interest in intramuscular injection of 17 alpha-hydroxyprogesterone caproate (17P). 17P is a weakly acting, naturally occurring progesterone metabolite, which when coupled with caproate dextran works as a long-acting progestin when administered intramuscularly. 17P is now commercially available as Makena™, (K-V Pharmaceutical Company, St. Louis, MO.) but is also manufactured locally by compounding pharmacies. Intravaginal progesterone suppositories have also been investigated.
On February 3, 2011, Makena™, hydroxyprogesterone caproate injection for intramuscular use, was approved by the FDA through the premarket approval (PMA) process. The product, formerly called Gestiva, is indicated to reduce preterm birth in women with a singleton pregnancy that have a history of singleton spontaneous preterm birth. Makena is not intended for use in women with multiple gestations or in women with other risk factors for preterm birth
March 31, 2011 the Food and Drug Administration announced that in order to support access to this important drug, at this time the FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products.
The use of progesterone suppositories during pregnancy for the prevention of preterm birth in high-risk women is currently under investigation. Progesterone suppositories are usually compounded by individual pharmacists and consist of progesterone suspended in a cocoa butter type base. Upon insertion, the warmth of the body causes the suppository to melt and release the progesterone.