SKYLA(Levonorgestrel 13.5mg; intrauterine system)
SKYLA Rx
Pharmacological Class:
Progestin IUD.
Active Ingredient(s):
Levonorgestrel 13.5mg; intrauterine system.
Company
Bayer Healthcare Pharmaceuticals Inc.
Indication(s):
Prevention of pregnancy for up to 3 years.
Pharmacology:
The mechanism by which continuously released levonorgestrel (LNG) enhances contraceptive effectiveness of Skyla has not been conclusively demonstrated. Studies of Skyla and similar LNG intrauterine system prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium.
After insertion into the uterine cavity with Skyla, 13.5mg of LNG was released in vivo at a rate of approximately 14mcg/day after 24 days. This rate decreases progressively to 5mcg/day after 3 years. The average release rate of LNG is approximately 6mcg/day over a period of 3 years.
Clinical Trials:
The efficacy of Skyla was demonstrated in a multicenter, randomized open label study conducted in 11 countries involving healthy women aged 18–35, 1,432 of whom received Skyla.
The primary endpoint was the pregnancy rate calculated as the Pearl Index (PI) in women aged 18–35 years to assess contraceptive reliability. The PI was calculated based on 28-day equivalent exposure cycles; eva luable cycles excluded those in which back-up contraception was used unless a pregnancy occurred in that cycle. Skyla-treated women provided 15,763 eva luable 28-day cycle equivalents in the first year and 39,368 eva luable cycles over the 3 year treatment period. The PI estimate for the first year of use based on the 5 pregnancies that occurred after the onset of treatment and within 7 days after Skyla removal or expulsion was 0.41 with a 95% upper confidence limit of 0.96. The cumulative 3-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan- Meier method was 0.9 per 100 women or 0.9% with a 95% upper confidence limit of 1.7%. About 77% of women wishing to become pregnant conceived within 12 months after removal of Skyla.
Legal Classification:
Rx
Adults:
See full labeling. Insert into uterine cavity as directed. Reexamine and eva luate 4–6 weeks after insertion; then yearly or more if needed. Remove or replace after 3 years.
Children:
Pre-menarche: not recommended.
Contraindication(s):
Post-coital contraception. Congenital or acquired uterine anomaly including fibroids. Acute or history of pelvic inflammatory disease (PID) unless there has been a subsequent intrauterine pregnancy. Postpartum endometritis or infected abortion in past 3 months. Uterine or cervical neoplasia. Breast or other progestin-sensitive cancer. Uterine bleeding of unknown etiology. Untreated acute cervicitis or vaginitis. Active liver disease or tumor. Conditions associated with increased susceptibility to pelvic infections. Retained IUD. Pregnancy.
Warnings/Precautions:
eva luate for ectopic pregnancy. Risk of spontaneous abortion, miscarriage, sepsis, premature labor or delivery, congenital anomalies: remove if pregnant. Consider risks of PID before using. Bleeding pattern alterations: exclude endometrial pathology prior to insertion in women with persistent bleeding. Risk of perforation, expulsion and ovarian cysts. Consider removal if coagulopathy, migraine, transient cerebral ischemia, severe headache, marked increase in BP, severe arterial disease, uterine/cervical malignancy, or jaundice occurs. May be scanned with MRI under specific conditions. Nursing mothers.
Interaction(s)
Caution with anticoagulants; consider removal. May be antagonized by barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, nevirapine, oxcarbazepine, phenytoin, rifabutin, rifampin, St. John’s wort, topiramate. May be affected by HIV PIs or NNRTIs. May be potentiated by CYP3A4 inhibitors (eg, ketoconazole, itraconazole).
Adverse Reaction(s)
Bleeding pattern alterations, vulvovaginitis, abdominal/pelvic pain, acne/seborrhea, ovarian cyst, headache; ectopic pregnancy, intrauterine pregnancy, sepsis, PID, perforation, expulsion.
How Supplied:
System—1
LAST UPDATED:
3/18/2013
Skyla宫内节育器已被美国FDA批准上市
Skyla宫内节育器已被美国食品药品管理局(FDA)批准上市。该设备的生产商拜耳医疗保健公司美国医学事务部主管兼副总裁Pamela A. Cyrus博士在新闻发布会上表示，这是近12年来首个进入美国市场的新型宫内节育器(IUD)。
根据生产商的说法，从2月11日开始患者就可以凭医生处方购买Skyla(宫内左炔诺孕酮释放系统)13.5 mg了。
加利福尼亚州托伦斯市Harbor–UCLA医学中心的妇产科教授Anita L. Nelson博士指出：“Skyla预防妊娠的有效率达到99%以上。并且，Skyla可用于经产或从未生育的妇女，对于在未来3年内不希望妊娠的妇女而言是一种重要的避孕新选择。”
Skyla的获准得到一项Ⅲ期试验数据的支持，在该研究中有1,432例年龄18~35岁的妇女使用这种设备避孕。这是在欧洲、拉丁美洲、美国和加拿大的11个国家进行的一项随机开放标记研究。研究排除了产后6周以内、有异位妊娠病史、有临床显著卵巢囊肿以及HIV或性传播感染高危的妇女。
主要疗效终点为基于28天等值暴露周期使用Pearl指数计算得出的妊娠率，用于评估避孕的可靠性。在第1年内，接受Skyla治疗的妇女提供了15,763个可评估的28天周期的数据，在3年治疗期间，共提供了39,368个可评估周期的数据。
基于开始治疗后和Skyla取出或排出后7天内发生的5次妊娠，第1年使用的PI估计值为0.41，95%置信区间上限为0.96。
在接受Skyla治疗的妇女中，22%因不良事件而停止该治疗。发生率超过5%的不良反应包括外阴阴道炎(20%)、腹部/盆腔疼痛(19%)、痤疮/脂溢性皮炎(15%)、卵巢囊肿(13%)、头痛(12%)、痛经(9%)、乳房疼痛/不适 (9%)、出血增加(8%)和恶心(6%)。
Skyla T型支架的测量值为28 mm×30 mm，置入管的外径为3.8 mm。在取出Skyla之后，妇女可立即妊娠。根据研究数据，有77%希望受孕的妇女在取出Skyla后第1年内成功妊娠。