Oral misoprostol solution measures up to tablet formulation for labour induction

The off-label oral solution of misoprostol proves noninferior to the licensed oral tablet for induction of labour, with no significant difference in the occurrence of vaginal delivery within 24 hours, according to a study.

In an intention-to-treat (ITT) analysis, 47.4 percent of women receiving the 25-μg oral solution and 43.9 percent of those receiving the 25-μg oral tablet delivered vaginally, establishing noninferiority with an absolute risk difference of 3.4 percent (95 percent confidence interval [CI], −3.2 to 10.0). [BJOG 2024;doi:10.1111/1471-0528.17986]

Fewer misoprostol doses were required to achieve active labour in women receiving oral solution vs oral tablet (5.7 vs 6.1; p=0.007). But no significant differences were seen in other outcomes including time from induction to delivery (26.5 vs 28.0 hours; p=0.13), total number of vaginal deliveries (82.1 percent vs 85.2 percent; p=0.24), and need for additional methods (29.7 percent vs 31.1 percent; p=0.66).

Finally, maternal and neonatal safety outcomes were similar in the oral solution and oral tablet arms. Specifically, caesarean section was performed in 17.8 percent and 14.8 percent of women in the respective arms, with foetal distress (35.9 percent vs 38.5 percent) and labour dystocia (29.5 percent vs 29.2 percent) being the most common indications. Meanwhile, the percentage of composite severe adverse neonatal outcome (ie, Apgar <7 at 5 min, umbilical artery pH <7.0, or admission to the neonatal intensive care unit) was 6.4 percent in the oral solution arm vs 3.9 percent in the oral tablet arm.        

There was no case of early maternal or neonatal death documented before discharge.

“To the best of our knowledge, this is the first trial comparing 25-μg oral solution of misoprostol with the 25-μg oral tablet of misoprostol regarding clinical effects. It shows fewer required doses of oral solution to achieve active labour compared to the oral tablet. A plausible mechanism for this is a proposed higher bioavailability of oral solution compared with oral tablet,” the investigators said. [Front Pharmacol 2020:11:50]

“There is a view among clinicians that the 25-μg oral tablet is more accurate in dosing and thus safer than the oral solution. This view is not supported by the aforementioned bioavailability study, which showed the preparations to be comparable, and that the variation in plasma concentration of oral solution of misoprostol appeared more stable than for the oral tablet,” they noted. [Front Pharmacol 2020:11:50]

The investigators emphasized that with a standardized protocol for preparation and administration, the oral solution offers a low-cost treatment modality that is advantageous in both low- and high-resource settings.

“With an increasing proportion of childbirths being induced, it is important to use a method that is effective, safe, and comes at a reasonable cost. The oral tablet is currently up to 43 times more expensive than the oral solution for induction of labour with eight doses,” they pointed out.

“For a hospital with close to 7,500 deliveries per year, this incurs an increased cost of EUR 193,500 per year, calculated on a 30-percent induction of labour rate. For a smaller hospital with around approximately 1,700 deliveries the cost difference is EUR 43,860 per year, calculated on a 30-percent induction of labour rate,” they added.

Nevertheless, the investigators highlighted the significant advantage of the oral tablet’s ease of self-administration. “Therefore, the oral tablet preparation may be more suitable for outpatient induction of labour.” [Acta Obstet Gynecol Scand 2020;99:222-230; Acta Obstet Gynecol Scand 2020;99:1396-1402; Dan Med J 2023;70:A04220232]

The ITT population included 874 women who had no history of caesarean section; had an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks; had a normal cardiotocography; and were scheduled for IOL. These women were randomly assigned to misoprostol either as a 25-μg oral solution (n=437, mean age 33.1 years, 70.7 percent nulliparous) or a 25-μg oral tablet (n=437, mean age 32.6 years, 70.7 percent nulliparous) every 2 hours for a maximum of eight doses. The mean gestational age at labour induction was 281 days in both arms.