己酸羟孕酮注射液
Makena(hydroxyprogesterone caproate injection)
适应症
女用长效避孕药
已获准用于有≥1次自发性早产史的孕妇以降低早产风险，并用于预防早产功效。
MAKENA Rx
Generic Name and Formulations:
Hydroxyprogesterone caproate 250mg/mL; for deep IM inj; contains castor oil, benzyl benzoate, benzyl alcohol.
Company:
Ther-Rx Corporation
Indications for MAKENA:
To reduce risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. Not intended for use in patients with multiple gestations or other risk factors for preterm birth.
Adult Dose for MAKENA:
Begin treatment between 16 weeks 0 days and 20 weeks 6 days gestation. Inject slowly (over 1 minute or longer) into upper outer quadrant of gluteus maximus. 250mg IM once weekly. Continue until Week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever comes first.
Children's Dose for MAKENA:
Not applicable.
Pharmacological Class:
Progestin.
Contraindications:
Current or history of thrombosis or thromboembolic disorders. Breast or other hormone-sensitive cancers. Undiagnosed abnormal genital bleeding. Cholestatic jaundice of pregnancy. Hepatic adenoma or carcinoma. Uncontrolled hypertension.
Warnings/Precautions:
Conditions aggravated by fluid retention (eg, preeclampsia, migraine, asthma, seizures, cardiac or renal dysfunction). Monitor diabetics and for depression. Hepatic impairment. Discontinue if depression, thromboembolic events or allergic reactions occur. Reevaluate if jaundice or hypertension occurs. Not for use in stopping active preterm labor. Pregnancy (Cat. B) (limited data on 1st trimester use). Nursing mothers: not recommended; discontinue upon delivery.
Interactions:
May affect metabolism of drugs metabolized by CYP1A2, CYP2A6, or CYP2B6 (eg, theophylline, tizanidine, clozapine, nicotine, acetaminophen, efavirenz, bupropion, methadone).
Adverse Reactions:
Inj site reactions (pain, swelling, pruritus, nodule), urticaria, pruritus, GI upset; pregnancy-related fetal and maternal complications.
How Supplied:
Multidose vial (5mL)—1
FDA批准Makena获准用于预防早产
美国食品药品管理局(FDA)和K-V制药公司宣布，己酸羟孕酮注射剂 (hydroxyprogesterone caproate injection，Makena) 已获准用于有≥1次自发性早产史的孕妇以降低早产风险。本品不适用于多胎妊娠(如双胎妊娠)或有其他早产危险因素的女性。
FDA审查了一项多中心随机双盲临床研究中本品的安全性和疗效数据。这项研究纳入463名年龄介于16~43岁、既往有1次自发性早产史的单胎妊娠女性。结果显示，本品治疗组有37%的女性于37孕周之前分娩，而对照组有55%。
在另一项研究中，研究者对参加对照试验的母亲所生孩子的发育情况进行了评估。结果证实，无论其母亲在随机试验中接受了何种疗法，所有孩子在年龄2.5~5岁时均达到了同一发育目标。目前有一项验证性研究正在进行中，之后会针对婴儿开展一项相似的随访研究，大概在2018年完成，该研究预计将纳入580~750名婴儿。
Makena的最常见不良反应包括注射部位疼痛、肿胀或瘙痒，以及荨麻疹、恶心和腹泻。严重不良反应少见。
Makena禁用于有以下任何一种情况的女性：当前或既往曾患有血栓症或血栓栓塞性疾病；已知患有乳腺癌或疑似乳腺癌，其他激素敏感性癌症，或有这些癌症的病史；未经诊断的与妊娠无关的异常阴道流血；妊娠期胆汁淤积性黄疸；肝脏良、恶性肿瘤或活动性肝病；高血压控制不良。
Makena由医护人员给药，于16~20孕周开始，每周肌注1次，一直持续至37孕周结束或至分娩(以先发生者为准)。
根据能够合理预测临床收益的替代终点收益(在本批准令中是指降低在37孕周前分娩的风险)，FDA基于加速审批法规批准了Makena这一具有应用前景的药物。根据上述法规，生产厂家必须在产品获批后开展进一步研究以证实其确实能产生临床收益。
FDA最初于1956年批准商品名为Delalutin的己酸羟孕酮用于孕妇，获准的适应证包括先兆流产。2000年，原生产厂家申请Delalutin撤市，撤市原因与安全性无关。
First drug to prevent premature births
First drug to prevent premature births Product: Makena
Company: Ther-Rx
Pharmacologic class: Progestin
Active ingredient: Hydroxyprogesterone caproate 250 mg/mL; for deep intramuscular (IM) injection; contains castor oil, benzyl benzoate, benzyl alcohol.
Indication: To reduce risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. Not intended for use in patients with multiple gestations or other risk factors for preterm birth.
Pharmacology: Hydroxyprogesterone caproate is a synthetic progestin that is indicated to reduce the risk of preterm birth in certain at-risk women. After IM administration, hydroxyprogesterone caproate reaches peak levels in about three to seven days in nonpregnant women. It is highly bound to plasma proteins and is extensively metabolized in the liver by several metabolic pathways. Both conjugated metabolites and free steroids are eliminated via urinary and fecal routes.
Clinical trials: A multicenter, randomized, double-blind, vehicle-controlled trial involving 463 pregnant women was conducted to assess the safety and efficacy of hydroxyprogesterone caproate in reducing the risk of spontaneous preterm birth. The study enrolled women aged 16 to 43 years with a history of singleton spontaneous preterm birth who were between 16 weeks 0 days and 20 weeks 6 days gestation with a singleton pregnancy. At the time of randomization, ultrasound was used to confirm gestational age and the absence of any known fetal abnormality. Women with prior progesterone treatment or heparin use were excluded, as were those with a history of thrombotic disease or maternal/obstetrical complications.
Compared with treatment with the vehicle control, treatment with hydroxyprogesterone caproate reduced the proportion of women who delivered preterm at <37 weeks (-17.8%). The proportions of women who delivered at <35 weeks and <32 weeks were also lower in the group given the study drug (-9.4% and -7.7%, respectively). There was no overall survival advantage to treatment with the study drug due to a higher rate of stillbirth and miscarriage; studies are continuing.
Adults: Begin treatment between 16 weeks 0 days and 20 weeks 6 days gestation. Inject slowly (over one minute or longer) into upper outer quadrant of gluteus maximus. 250 mg IM once weekly. Continue until Week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever comes first.
Children: Not applicable.
Contraindications: Current or history of thrombosis or thromboembolic disorders. Breast or other hormone-sensitive cancers. Undiagnosed abnormal genital bleeding. Cholestatic jaundice of pregnancy. Hepatic adenoma or carcinoma. Uncontrolled hypertension.
Warnings/Precautions: Conditions aggravated by fluid retention (e.g., pre-eclampsia, migraine, asthma, seizures, cardiac or renal dysfunction). Monitor diabetics and for depression. Hepatic impairment. Discontinue if depression, thromboembolic events, or allergic reactions occur. Reevaluate if jaundice or hypertension occurs. Not for use in stopping active preterm labor. Pregnancy (Cat. B) (limited data on first-trimester use). Nursing mothers: not recommended; discontinue upon delivery.
Interactions: May affect metabolism of drugs metabolized by CYP1A2, CYP2A6, or CYP2B6 (e.g., theophylline, tizanidine, clozapine, nicotine, acetaminophen, efavirenz, bupropion, methadone).
Adverse reactions: Injection site reactions (pain, swelling, pruritus, nodule), urticaria, pruritus, GI upset; pregnancy-related fetal and maternal complications.
How supplied: Multidose vial (5 mL)—1
Makena 250 mg/mL IM Oil
完整使用资料附件：
http://www.makena.com/pages/oat/purchasing-and-stocking-makena/default.aspx
http://www.kvph.com/Makena/17p-alpha-hydroxyprogesterone-caproate.aspx