Hydroxyprogesterone caproate injection (Makena): A synthetic progestin, hydroxyprogesterone caproate intramuscular injection to reduce the risk of preterm birth

April 1, 2011

New indication: Hydroxyprogesterone caproate injection was approved by FDA in February to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of at least 1 spontaneous preterm birth.

A synthetic progestin, hydroxyprogesterone caproate intramuscular injection to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of at least 1 spontaneous preterm birth

Hydroxyprogesterone caproate injection was approved on February 4 under FDA's accelerated approval regulations that allow promising drugs to be marketed in the United States based on surrogate end point data that likely predicts an important clinical benefit. Hydroxyprogesterone caproate injection is not intended for use in women with multiple gestations or other risk factors for preterm birth.

Efficacy. Efficacy data supporting hydroxyprogesterone caproate injection's ability to reduce the risk of spontaneous preterm birth is derived from a multicenter, randomized, double-blind, placebo-controlled clinical trial. In this trial, 463 pregnant women aged 16 to 43 years who were pregnant with a single fetus and had a history of a prior spontaneous preterm birth (<37 weeks gestation) were enrolled. Among women treated with Makena (n=310), 37% delivered preterm as compared with 55% of women in the placebo group (n=153) (difference for delivering prior to 37 weeks, -17.8%, 95% CI, -28.0% to -7.4%; <35 weeks, -9.4%, 95% CI, -19.0% to -0.4%; and <32 weeks, -7.7%, 95% CI, -16.1% to -0.3%). Despite these benefits, an overall survival benefit was not demonstrated in this trial due to a higher rate of miscarriages and stillbirths in the Makena group compared to placebo group. In a follow-up study evaluating children born to the above studied women (n=287, 79.9% of eligible infants), the proportion of children (aged 2-5 years) diagnosed with developmental delay [using the Ages & Stages Questionnaire (ASQ)] was similar between groups.

Dosing. Hydroxyprogesterone caproate injection is administered intramuscularly beginning at 16 weeks/0 days to 20 weeks/6 days of gestation at a dose of 250 mg (1 mL) once weekly and continued until week 37 of gestation or delivery, whichever occurs first. Hydroxyprogesterone caproate injection is contraindicated in patients with current or a history of thromboembolic disorders, known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions, undiagnosed abnormal vaginal bleeding unrelated to pregnancy, cholestatic jaundice of pregnancy, liver tumors or active liver disease, or uncontrolled hypertension.