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Hydroxyprogesterone caproate (INN, USAN, JAN), or 17α-hydroxyprogesterone caproate, also known as hydroxyprogesterone hexanoate (BANM), marketed under brand names including Delalutin, Proluton, Makena, Prodrox, Hylutin, and many others, is a steroidal progestin (that is, a synthetic progestogen) and 17α-hydroxyprogesterone derivative that is related to other derivatives of 17α-hydroxyprogesterone such as medroxyprogesterone acetate and megestrol acetate. It is an ester of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid).〔 Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the United States (U.S.) Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. It is also sold as Proluton throughout Europe.〔 The U.S. FDA approved Makena from KV Pharmaceutical (previously named as Gestiva) on February 4, 2011 for prevention of preterm delivery in women with a history of preterm delivery, sparking a pricing controversy. ==Safety== The use of hydroxyprogesterone caproate in pregnancy to prevent preterm birth in women with a history of preterm delivery between 20 weeks and 36 weeks and 6 days is supported by the Society of Maternal Fetal Medicine Clinic Guidelines put out in May 2012 as Level I and III evidence, Level A recommendation.〔SMFM Clinical Guideline: Progesterone and preterm birth prevention: translating clinical trials data into clinical practice, AJOG May 2012〕 Level I evidence refers to a properly powered randomized controlled trial, and level III evidence is support from expert opinion, while a Level A recommendation confers that the recommendation is made based on good and consistent scientific evidence. Hydroxyprogesterone caproate 250 mg IM weekly preferably starting at 16–20 weeks until 36 weeks is recommended. In these women, if the transvaginal ultrasound cervical length shortens to <25 mm at < 24 weeks, cervical cerclage may be offered. In the 2013 study the guideline recommendation is based on by 〔Meirs et al. NEJM 2003〕 there was also a significant decrease of neonatal morbidity including lower rates of necrotizing enterocolitis (0 in treatment group vs 4 in control), intraventricular hemorrhage (4 in the treatment group compared with 8 in the control for relative risk of 0.25), and need for supplemental oxygen (14% in treatment group vs 24% in placebo for relative risk of 0.42). Furthermore, this study contained 463 patients, 310 of whom received injection. Of these patients, 9 had infants with congenital malformations (2%), but there was no consistent pattern and none involved internal organs. Hydroxyprogesterone caproate is currently (as of June 2014) pregnancy category B, meaning there is no evidence of fetal risk with use of this drug during pregnancy. Although this is now the recommendation, this has not always been the case. 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".〔Dodd JM, Flenady V, Cincotta R, Crowther CA; ''The Cochrane Database of Systematic Reviews'' 2006 Issue 1〕 There was a similar conclusion from a review by Marc Keirse of Flinders University. Three clinical studies in singleton pregnancies of 250 mg/week of intramuscular hydroxyprogesterone caproate have all shown a trend for an increase in pregnancy loss due to miscarriage compared to placebo.〔Meis PJ et al. Prevention of Recurrent Preterm Delivery by 17 Alpha-hydroxyprogesterone Caproate. NEJM, 2003: vol 348, no 24, pg 2379-2385.〕〔Keirse MJNC, Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol 1990 February; 97:149.〕 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 hydroxyprogesterone caproate with increased risk of second trimester miscarriage and stillbirth.〔(Advisory Committees: CDER 2006 Meeting Documents )〕 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 hydroxyprogesterone caproate.〔Hendrix AG, et al. Embriotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate. Teratology 1987 February. 35 (1): 129.〕 , hydroxyprogesterone caproate was 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 hydroxyprogesterone caproate formulation may not be beneficial for pregnancy.〔Duke University Medical Center, New England Journal of Medicine, correspondence, vol 349.〕 Of note, the above-mentioned NEJM study by Meirs et al. compares the effect of hydroxyprogesterone caproate (with the castor oil component) to castor oil injection as the placebo. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Hydroxyprogesterone caproate」の詳細全文を読む スポンサード リンク
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