17α-Hydroxyprogesterone caproate is a synthetic steroid hormone

Steroid hormone

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

 that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester

Ester

Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

 derivative of 17α-hydroxyprogesterone

17-Hydroxyprogesterone

17-Hydroxyprogesterone is a C-21 steroid hormone produced during the synthesis of glucocorticoids and sex steroids.As a hormone, 17OHP also interacts with the progesterone receptor.-Production:...

 formed from caproic acid (hexanoic acid).

17α-Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb

Bristol-Myers Squibb

Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...

, which was approved by the U.S. Food and Drug Administration

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (FDA) in 1956 and withdrawn from marketing in 1999.

The US FDA approved Makena from KV Pharmaceutical

KV Pharmaceutical

KV Pharmaceutical Company is an American drug company that brings generic and non-branded pharmaceutical products to the market. Headquartered in St...

 (previously named as Gestiva) on February 4, 2011 for prevention of preterm delivery

Premature birth

In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...

 in women with a history of preterm delivery, sparking a pricing controversy.

Safety

The use of 17-hydroxyprogesterone caproate in pregnancy to prevent preterm birth is not recommended without further study according to two authorities. A 2006 Cochrane Review concluded "...important maternal and infant outcomes have been poorly reported to date... information regarding the potential harms of progesterone therapy to prevent preterm birth is limited". There was a similar conclusion from a review by Marc Keirse of Flinders University

Flinders University

Flinders University, , is a public university in Adelaide, South Australia. Founded in 1966, it was named in honour of navigator Matthew Flinders, who explored and surveyed the South Australian coastline in the early 19th century.The university has established a reputation as a leading research...

. Three clinical studies in singleton pregnancies of 250 mg/week of intramuscular

Intramuscular injection

Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

 17-hydroxyprogesterone caproate have all shown a trend for an increase in pregnancy loss due to miscarriage compared to placebo. The FDA expressed concern about miscarriage at the 2006 advisory committee meeting; the committee voted unanimously that further study was needed to evaluate the potential association of 17OHP-C with increased risk of second trimester miscarriage and stillbirth. A toxicology study in rhesus monkeys resulted in the death of all rhesus fetuses exposed to 1 and 10 times the human dose equivalent of 17-hydroxyprogesterone caproate. , 17-hydroxyprogesterone caproate is a category D progestin according to the FDA (that is, there is evidence of fetal harm). There is speculation that the castor oil in the 17-hydroxyprogesterone caproate formulation may not be beneficial for pregnancy.

Synthesis

Hydroxyprogesterone caproate can be prepared by the following sequence:

Makena

A 2011 decision by the USFDA was going to result in driving "up the [US] cost of an available medication from about $300 to $30,000 — about a 100-fold increase — with minimal added clinical benefit". However, the USFDA said it would not go after compounding pharmacies that filled prescriptions, and KV Pharmaceutical announced a lower price.

Sources

• FDA Reproductive Health Drugs Advisory Committee. August 29, 2006 Meeting to discuss NDA 21-945 Gestiva (Adeza Biomedical)
  17α-hydroxyprogesterone caproate injection, 250 mg/mL, for the proposed indication: prevention of preterm delivery in women with a history of a prior preterm delivery.
• Adeza Biomedical (October 23, 2006) Receives FDA Approvable Letter For Gestiva
• Adeza gets orphan drug designation for Gestiva (January 31, 2007)
• Cytyc Acquires Adeza Biomedical Corporation (April 3, 2007)
  Adeza's name changed to Cytyc
  Cytyc
  Cytyc Corporation was a company engaged in the design, development, manufacture, and marketing of clinical products that focus on women’s health. Its products covered a range of women's health applications, including cervical cancer screening, breast cancer risk assessment, treatment of excessive...
  
  Prenatal Products Corp.
• womens health (October 23, 2006) 17-hydroxyprogesterone