Hydroxyprogesterone caproate, a synthetic form of the
hormone progesterone, is now FDA approved to help reduce the risk for preterm
delivery in pregnant women who have a history of spontaneous birth.
Pregnant women at risk for preterm delivery can receive
a once-weekly injection of hydroxyprogesterone caproate (Makena) into the hip.
Treatment should begin at 16 weeks and no later than 21 weeks gestation. The
injections are indicated only for women who are carrying a single fetus and who
have no other risk factors for pregnancy.
“Preterm birth is a significant public health issue
in the United States,” Sandra Kweder, MD, deputy director of the
Office of New Drugs in the FDA’s Center for Drug Evaluation and Research,
said in a press release. “This is the first drug approved by the FDA that
is indicated to specifically reduce this risk.”
It is estimated that half a million babies are born
prematurely in the US each year.
The therapy was approved under the FDA’s
accelerated approval regulations, which allow promising drugs to be approved
based on a surrogate endpoint benefit that is reasonably likely to predict a
clinical benefit. Under these regulations, the manufacturer must conduct
additional studies to demonstrate that the drug does, in fact, have a clinical
benefit. An international trial is ongoing to investigate whether there is also
improvement in the outcome of babies born to women given hydroxyprogesterone
In a multicenter, randomized, double blind, clinical
trial, 37% of pregnant women with a history of prior spontaneous preterm birth
who were given hydroxyprogesterone caproate delivered before 37 weeks compared
with 55% of women who served as a control group. Results of another study that
evaluated the development of children born to mothers in the controlled trial
showed that children aged 2.5 years to 5 years reached similar developmental
targets, regardless of the mother’s treatment. This study is ongoing and
will be followed by a similar infant follow-up study of up to 750 infants that
is slated for completion in 2018.
Pain, swelling or itching at the injection site were the
most common adverse effects reported with hydroxyprogesterone caproate. Serious
adverse reactions were rare; there was a single report each of pulmonary
embolism and an infection at the injection site.
The FDA originally approved hydroxyprogesterone caproate
under the trade name Delalutin in 1956 for use in pregnant women. The original
manufacturer requested withdrawal of Delalutin from the market in 2000 for
reasons unrelated to safety.
The drug is sponsored by Hologic, Inc., based in