17 α-Hydroxyprogesterone caproate (Makena™): in the prevention of preterm birth

17 α-hydroxyprogesterone caproate is a synthetic progestin of which there is now a US FDA-approved formulation available for intramuscular administration (Makena™) to reduce the risk of preterm birth. Intramuscular 17 α-hydroxyprogesterone caproate (identical in formulation and manufacturing process to Makena™, thus hereafter referred to as Makena™) 250 mg once weekly, initiated at 16-20 weeks' gestation, was effective in reducing the risk of preterm birth in women with a singleton pregnancy at high risk of delivering preterm in a large, well designed, placebo-controlled trial (n = 463 randomized). Rates of delivery before 37 (primary endpoint), 35, or 32 weeks' gestation were significantly lower with Makena™ than with placebo, corresponding to relative risk reductions of 34%, 33%, and 42%, respectively. The benefit of the drug in reducing the risk of preterm birth was observed when deliveries were spontaneous (but not when indicated because of complications) and regardless of maternal race. In addition, there was a significantly lower rate of several adverse fetal/neonatal outcomes among infants of women who received Makena™ than among infants of placebo recipients, including necrotizing enterocolitis, need for supplemental oxygen, birth weight of <2500 g, and intraventricular hemorrhage. Makena™ was generally well tolerated in pregnant women in this trial. Moreover, fetal exposure to the drug appeared to be safe according to a 2- to 5-year follow-up of the study, with no evidence of a detrimental effect of the drug on child neurodevelopment and a low overall incidence (≈2%) of reproductive or genital abnormalities that was not significantly different from placebo.