This MFMU study has been challenged because of the unexpectedly high preterm delivery rate in the placebo arm (Romero, 2013). One explanation for this high rate in the placebo group was asymmetry in the risks of recurrence. Indeed, 41 percent of the control group had ::2 prior preterm births compared with only 28 percent in the 17-0HP-C group. Another concern was that the injection dosage of 17-0HP-C, which was 250 mg weekly, was empirically chosen (Caritis, 2014). Only later reports described the pharmacokinetics of 17-0HP-C (Caritis, 2012). Nonetheless, the Society for Maternal-Fetal Medicine (2017a) recently reairmed the use of 17-0HP-C, rather than vaginal progesterone, for prevention of recurrent preterm birth.
Sharma and associates (2008) reported that the metabolism of 17-0HP-C was predominantly mediated by the CYP3A enzymatic system. Thus, other agents that induce or inhibit this enzymatic system as well as hepatic impairment may alter drug levels. They also showed that 17-0 HP -C is not converted after administration to the primary progesterone metabolite, 17a-hydroxyprogesterone. The relative binding ainity of 17-0 HP -C to progesterone receptors approximates only 30 percent of that by progesterone (Attardi, 2007). Because synthetic 17-0HP-C is not converted to a naturally occurring progestogen and is not superior to progesterone in eliciting a hormonal response via the classic steroid-receptor mediated pathway, alternative pathways are now being considered to explain its eicacy (Manuck, 2011).
Caritis and colleagues (2012) examined 61 women receiving 17-0HP-C therapy and found that the hlf-life was relatively long (median 16.2 days). Pharmacokinetic parameters were ffected by maternal body habitus and varied widely between subjects. In addition, 17 -OHP-C crossed the placental barrier and was detectible in cord plasma 44 days ater the last maternal injection (Caritis, 2012). Despite this, evidence to date suggests that 17-0HP-C is safe for the fetus. No abnormalities, including abnormal genitlia, were found in a 48-month follow-up study of infants exposed in the 2003 MFMU Network trial (Northen, 2007).
here are special concerns involving 17-0HP-C and subsequent price-gouging claims (Cohen, 2011; Romero, 2013). In 2011, the FDA gave temporary approval to V Pharmaceutical to market 17 -OHP-C under the brand name Makena. Because regulations prohibited compounding, there was no competitor for this relatively inexpensive drug, and Makena was priced at $1500 per injection. This caused widespread concern because the cumulative cost of Makena would be more than $30,000 per pregnancy.
Use of 17-0HP-C at Parkland Hospital
A program for implementation of 17-0HP-C was incorporated at Parkland Hospital in 2012. Given the concerns above,
Preterm Birth 81.7
TABLE 42-6. Prior Obstetrical History of 430 Women with Births ;35 weeks and Recurrence Rates After 17-0HP-C at Parkland Hospital
Prior Birth <35 Weeks Recurrence Ratea No. No. Rate p valueb
Overall 16.8% 430 106 25% 1.0
Para 1 18% 141 44 31 % 1.0
Para 2: