Evidence-Based. Clearly Delivered.
Evidence-Based. Clearly Delivered.
FDA approval for Makena, a drug used to reduce risk for preterm birth, has been formally withdrawn. The withdrawal also includes all generics (17-alpha hydroxyprogesterone caproate [17-OHPC]). Regarding any current medication in distribution, the FDA states that “Patients who have questions should talk to their healthcare provider.” Both ACOG and SMFM have addressed the situation.
Intramuscular 17-OHPC is not recommended for the primary prevention of preterm birth in patients with a history of spontaneous preterm birth
In summary, at this time, the body of evidence is equivocal regarding the effectiveness of 17-OHPC, and the referenced FDA action will limit access to 17-OHPC for patients
We agree with the FDA determination and discourage continued prescribing of 17-OHPC, including through compounding pharmacies
We agree with the FDA that there is no evidence of benefit with continued treatment
Patients currently receiving 17-OHPC can be counseled that the FDA’s Center for Drug Evaluation and Research (CDER) has not identified evidence of harm from discontinuation prior to 37 weeks of gestation
The authors of the PROLONG trial (Progestin’s Role in Optimizing Neonatal Gestation) reported on the use of 17α-hydroxyprogesterone caproate (17-OHPC) for the treatment of preterm birth (PTB)
In this study population, 250 mg 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death
On October 29, 2019, the FDA advisory committee recommended that the drug be withdrawn from the market (9 to 7 vote). On October 5, 2020, the Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market. At that time, the decision was made to hold further meetings and discussions. Based upon further follow-up, the CDER briefing materials for the Advisory Committee meeting (October 17-19, 2022) states
Makena has not been shown to improve neonatal outcomes from premature birth, is no longer shown to be effective for its approved use, and has known risks
The 1,708-person confirmatory trial designed to verify Makena’s clinical benefit instead failed to show that Makena has any benefit to newborns. Data from this trial, taken together with other evidence, also fail to show that Makena reduces the risk of recurrent preterm birth
For these and other reasons detailed herein, Makena should be withdrawn from the market
Meis Trial
Prolong Trial
Authors’ Conclusion
We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study
Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health
FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena
Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. (NEJM, 2003)
FDA Briefing Materials for Withdrawal of Makena Approval (2022)
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