General Information

Makena contains the active ingredient hydroxyprogesterone caproate, a synthetic progestin. The mechanism by which hydroxyprogesterone caproate reduces the risk of recurrent preterm birth is not known.

Makena is specifically indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

Makena is supplied as a solution for intramuscular injection. Makena should be aministered intramuscularly at a dose of 250 mg (1 mL) once weekly (every 7 days). Treatment should begin between 16 weeks, 0 days and 20 weeks, 6 days of gestation. Administration should be continued once weekly until week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever occurs first.

Clinical Results

FDA Approval
The FDA approval of Makena was based on a multicenter, randomized, double-blind, vehicle (placebo)-controlled clinical trial. The trial enrolled 463 women with a singleton pregnancy (age 16 to 43 years) who had a documented history of singleton spontaneous preterm birth (defined as delivery at less than 37 weeks of gestation following spontaneous preterm labor or premature rupture of membranes). The women were randomized to receive either Makena or vehicle at a dose of 250 mg administered weekly by intramuscular injection starting between 16 weeks, 0 days and 20 weeks, 6 days of gestation, and continuing until 37 weeks of gestation or delivery. Compared to controls, treatment with Makena reduced the proportion of women who delivered preterm at < 37 weeks. The proportions of women delivering at < 35 and < 32 weeks also were lower among women treated with Makena. The upper bounds of the confidence intervals for the treatment difference at < 35 and < 32 weeks were close to zero. After adjusting for time in the study, 7.5% of Makena-treated subjects delivered prior to 25 weeks compared to 4.7% of control subjects. A composite neonatal morbidity/mortality index evaluated adverse outcomes in livebirths. It was based on the number of neonates who died or experienced respiratory distress syndrome, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, proven sepsis, or necrotizing enterocolitis. Although the proportion of neonates who experienced 1 or more events was numerically lower in the Makena arm (11.9% vs. 17.2%), the number of adverse outcomes was limited and the difference between arms was not statistically significant.

Side Effects

Adverse events associated with the use of Makena may include, but are not limited to, the following:

• injection site reactions
• swelling
• pruritus
• nodule
• urticaria
• pruritus
• nausea
• diarrhea

Mechanism of Action

Makena contains the active ingredient hydroxyprogesterone caproate, a synthetic progestin. The mechanism by which hydroxyprogesterone caproate reduces the risk of recurrent preterm birth is not known.

Additional Information

For additional information regarding Makenae or preterm birth, please visit the Makena web page.