---------------------------------------------------------------
 部分中文BALZIVA处方资料（仅供参考）
---------------------------------------------------------------

分类名称
一级分类：妇产科用药 二级分类：雌激素类及抗雌激素类药
 
药品英文名
Estrsdiol/Norethisterone
 
药品别名
诺更宁、诺康律、克龄蒙
 
药理作用
雌二醇主要由卵巢成熟卵泡分泌，具有如下作用：1.促进女性性征和性器官的发育成熟。2.维持性征，参与月经周期的形成，促使子宫内膜增殖变厚，宫颈黏液增多，并增强子宫平滑肌收缩。3.较大剂量时可抑制下丘脑-垂体系统促性腺激素释放激素的分泌和抗催乳素作用。4.抗雄性激素作用。5.轻度水、钠潴留作用。6.降血中胆固醇和增加骨骼钙沉积作用。 17-β雌二醇主要作用为调节和维持妇女正常平稳的雌激素生理水平。本品不影响抗凝血酶因子Ⅲ，使血栓栓塞的危险降低。可改善心血管功能，适用于糖尿病、肝病、心血管疾病及肥胖的患者。 诺坤复、诺康律、诺更宁系列产品的主要成分为微粒化天然人雌激素17β-雌二醇，其化学结构、生理作用及代谢途径均与卵巢产生的内源性17β雌二醇完全一致，其在人体内的代谢过程是自然的，所有代谢产物都是已知的，并且也是在人体内自然发生的。甲基炔诺酮具有很强的孕激素作用，并有雄激素、雌激素和抗雌激素活性。与雌激素配合，周期性用于激素替代疗法。 克龄蒙是一种高效的雌激素-孕激素复方，其中含有孕激素醋酸环丙孕酮，有抗雄激素作用，可维持血清中脂蛋白水平的稳定，有助于预防心血管系统动脉硬化的发生，可保护子宫内膜，减少了内膜增生的危险性。本药能迅速缓解因激素缺乏而引起的更年期症状，还对皮肤和黏膜退化(尤其是泌尿生殖的黏膜)有明显改善作用，并对因雌激素缺乏而引起的骨质疏松有预防作用。
 
药动学
用雌二醇贴片后血浆内雌二醇水平迅速上升，达峰时间在22～24h之间，血中雌二醇浓度在150pmol/L左右，可维持3～7天。停用后，雌二醇浓度在24h内恢复至用药前水平。 苯甲酸雌二醇注射液在血液内，部分与β球蛋白结合，游离的雌二醇被组织利用。部分被肝脏破坏，或经胆汁排泄，再被肠道吸收，形成肠肝循环，其代谢产物多与硫酸或葡萄糖醛酸结合成酯后从尿中排出。
 
适应证
雌激素缺乏综合征。制剂注释与选择： 1.17-β雌二醇凝胶 凝胶剂经皮吸收进入体内，不经肝肠循环，无首关效应，避免了对肝脏的损害。适用于肝功能不良者。2.雌二醇皮肤贴膜剂 制剂中活性药膜层可通过皮肤直接向体循环释放药物，从而避免了口服药物的肝脏首关效应及其引发的治疗时的不良反应。得美素提供的雌激素可以在血中达到一个持续、均匀而稳定的生理浓度。缓释贴膜剂可3～4天用药一次。周效控释贴膜每周用药一次即可。3.诺坤复、诺康律、诺更宁采用微粒化技术保证了其口服后可迅速高效地吸收。采用独特的日历盘式包装，每个日历盘包装含28片药片。一天1片，使用方便，有助于提高服药的顺应性，可避免因中断治疗而出现的症状反复。(1)诺更宁：本品为17β-雌二醇/醋酸炔诺酮二相片，每片含雌二醇2mg(为半水合物)和醋酸炔诺酮1mg。适用于绝经后妇女补充雌激素，治疗雌激素缺乏综合征，使月经周期停止。(2)诺康律：本品为17β-雌二醇/醋酸炔诺酮三相片，蓝色片剂含雌二醇2mg，12片；白色片剂含雌二醇2mg和醋酸炔诺酮1mg，10片；红色片剂含雌二醇1mg，6片。适用于围绝经期妇女补充雌激素，治疗雌激素缺乏综合征，使月经周期规律化。4.克龄蒙 本药是一种雌-孕激素复方制剂，每一天历包装含有11片戊酸雌二醇，每片含戊酸雌二醇2mg；10片戊酸雌二醇与醋酸环丙孕酮复方片剂，每片含戊酸雌二醇2mg，醋酸环丙孕酮1mg。
 
禁忌证
对本品成分高度过敏者禁用。子宫、阴道或乳房有激素依赖性肿瘤、子宫内膜异位症者禁用。严重肝肾功能异常、既往或现有肝脏肿瘤、既往妊娠期间有过持续性瘙痒、妊娠期疱疹史、妊娠期耳硬化症恶化，血栓栓塞性疾病、镰状细胞性贫血、伴有血管病变的严重糖尿病、脂肪代谢先天异常、。Dubin-Johnson综合征、Rotor综合征、代谢性卟啉症患者禁用。孕妇及正在哺乳的妇女禁用。
 
注意事项
口服制剂用量不宜过大。
 
不良反应
可能出现轻度胃肠不适。贴片处皮肤可能有轻度发红或瘙痒，偶有皮疹。 可能有乳腺增大、乳房肿胀疼痛或出现分泌物、不规则流血、月经改变或闭经；偶见恶心、呕吐、腹胀，水肿、皮肤反应、头痛、偏头痛、胆石症、气喘、脱发，发生胆汁郁积症及胰腺炎、皮肤黄褐斑、舞蹈症。角膜曲度可能发生改变，不能戴隐形眼镜；性欲改变及卟啉症恶化、水钠潴留等。罕见静脉血栓。乳腺癌、子宫内膜癌也有报道。
 
用法用量
1.用于绝经期综合征、功能性子宫出血、原发性闭经、前列腺癌及退乳，雌激素水平低的替代疗法(需个体化剂量)。(1)口服①戊酸雌二醇片：每次服药2mg片，每天1次，饭后服用，或遵医嘱。药片应与水一起吞服。每经过21天的治疗后，必须停服此药至少一周。治疗过程中，根据患者情况，可将补佳乐剂量减至每天服用1mg。②诺坤复、诺更宁：采用独特的日历盘式包装，一天1片。③克龄蒙：服药时，把日历贴纸取出，贴在药片包装中央，使开始服药的日期对准标有“Start”(开始)字样。服药自标有“Start”(开始)字样处开始，按箭头方向服用，每天1片，直至服完21片。药片宜整片用水送服，停药7天后继续服用。(2)外用：①17-β雌二醇凝胶：每天将凝胶2.5g涂布于双臀、肩颈、腹壁、大腿皮肤上，药物经皮肤吸收。已绝经者每次1.25～2.5g(每半剂量尺相当于1.25g，含雌二醇0.75g)，每天1次，连用25天，停用5天；有子宫者应与孕酮合用，每天100mg，连用25天，停用5天；尚未绝经者，于周期第5天开始使用，每天1.25～2.5g，连用25天，于用药后的14天加用孕酮每天200～300mg，共用12天。②雌二醇控释贴片(周效)：每周1次，可采用连续治疗方案或连用3周停药1周方案，应每月常规联用10～12天的孕激素。如采用连续治疗方案可在任意时间开始使用孕激素。如采用连用3周停药1周方案，则应在周期的最后10～12天使用孕激素。③伊尔：每周用药1次，每片含雌二醇2.5mg，贴在下腹部或臀部皮肤上，共3次，停用1周。在最后5天每天服安宫黄体酮，每次4mg。④雌二醇控释贴片：每次1片，每周用2次，可以连续使用，也可连用3周，停药1周。连续使用者应每天连用一定剂量的孕激素，周期使用者应在周期的最后10天联用一定剂量的孕激素。⑤伊司乐：每次1片，每周用2次，连用3周，停药1周，最后5天加安宫黄体酮，每天4～5mg。肌注苯甲酸雌二醇注射液：一次1～2mg，一周2～3次。2.用于功能性子宫出血 肌注：苯甲酸雌二醇注射液：1mg～2mg，至血净后酌情减量，后期择日用黄体酮撤退。3.用于退奶 肌注：苯甲酸雌二醇注射液：每天2mg，不超过3天后减量或改小量口服药至生效。4.用于围绝经期妇女生理性补充雌激素 (1)口服：诺康律：每天1片，有月经的妇女在月经第5天开始服第1片(由蓝片开始)。其他妇女可以在任何一天开始服药。开始12天服用蓝片，其后10天服用白片，最后6天服用红片。①开始用激素替代疗法前，应作全面彻底的内科和妇科检查，特别是血压测量，乳房、腹部及妇科检查。用药期间每6个月应进行检查。在绝经后妇女用雌激素替代疗法有引发子宫内膜过度增生或子宫内膜癌的危险，故需每年检查1次。②口服制剂：患者在一天内的具体服药时间不拘，但如已选定某一特定时间(如早饭后)，则每天应在相同时间内服用。如果忘记按时服药，则应在12h内补服上。使用雌激素替代疗法的妇女胆囊炎的发病率升高。用药期间如果出现下列症状需立即停药：第一次发生偏头痛或频发少见的严重头痛、突发性感觉障碍、血栓性静脉炎或血栓栓塞的首发指征、胸痛、紧缩感、癫痫发作次数增加、待定的手术(提前6周)、固定术(如事故后)、发生黄疸、全身瘙痒、血压 升高、妊娠。③有子宫肌瘤、心脏病、癫痫、糖尿病及高血压患者慎用。有完整子宫的妇女如出现原因不明的阴道流血或曾用非对抗雌激素治疗过，应特别注意检查是否有子宫内膜过度刺激或恶变。④急慢性肝病或有肝病史的妇女，用药期间应定期检查肝功能。有静脉血栓栓塞性疾病应定期检查血液凝固的指标。⑤接受抗高血压治疗或有癫痫、高血压、偏头痛、糖尿病、气喘病或心力衰竭、静脉曲张、多发性硬化、卟啉症、手足搐搦、小舞蹈病、静脉炎史患者应在监护下用药。⑥少数良性或极少数恶性肝脏肿瘤患者，服用激素类药物后其中个别病例可能发生危及生命的腹腔内出血。因此，若发生异常的上腹部症状，且短时间内不自行消失，应告诉医生。(2)继发性闭经治疗前，应排除催乳素垂体瘤的可能。①17-β雌二醇凝胶含少量乙醇，个别患者可能有局部刺激感，不影响药效。②17-β雌二醇。
 
药物相应作用
本品与巴比妥、保泰松、利福平、酰胺咪嗪等肝药酶诱导剂合用可增加本品的代谢，降低疗效。 本品与口服降糖药或胰岛素合用，后者的剂量可能需要调整。
 
专家点评
雌二醇/炔诺酮的制剂，诺坤复、诺康律、诺更宁系列产品的主要成分为微粒化天然人雌激素17β-雌二醇，其化学结构、生理作用及代谢途径均与卵巢产生的内源性17β雌二醇完全一致，其在人体内的代谢过程是自然的，所有代谢产物都是已知的，并且也是在人体内自然发生的。甲基炔诺酮具有很强的孕激素作用，并有雄激素、雌激素和抗雌激素活性。与雌激素配合，周期性用于激素替代疗法。每天在相同时间内服用本药是起得好疗效的关键。

Brand Names: Aranelle, Balziva, Brevicon, Estrostep Fe, Femcon FE, Junel 1.5/30, Junel Fe 1.5/30, Junel Fe 1/20, Leena, Loestrin 21 1.5/30, Loestrin 24 Fe, Loestrin Fe 1/20, Microgestin 1.5/30, Microgestin FE 1.5/30, Modicon, Necon 0.5/35, Necon 1/35, Necon 7/7/7, Nortrel 0.5/35, Nortrel 7/7/7, Ortho-Novum 1/35, Ortho-Novum 7/7/7, Ovcon 35, Tilia Fe, Tri-Legest Fe, Tri-Norinyl, Zenchent

Generic Name: ethinyl estradiol and norethindrone (Pronunciation: ETH in il ess tra DYE ole and nor ETH in drone)

What is ethinyl estradiol and norethindrone (Aranelle, Balziva, Brevicon, Estrostep Fe, Femcon FE, Junel 1.5/30, Junel Fe 1.5/30, Junel Fe 1/20, Leena, Loestrin 21 1.5/30, Loestrin 24 Fe, Loestrin Fe 1/20, Microgestin 1.5/30, Microgestin FE 1.5/30, Modicon, Necon 0.5/35, Necon 1/35, Necon 7/7/7, Nortrel 0.5/35, Nortrel 7/7/7, Ortho-Novum 1/35, Ortho-Novum 7/7/7, Ovcon 35, Tilia Fe, Tri-Legest Fe, Tri-Norinyl, Zenchent)?
Ethinyl estradiol and norethindrone contains a combination of female hormones that prevent ovulation (the release of an egg from an ovary). This medication also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Ethinyl estradiol and norethindrone are used as contraception to prevent pregnancy. It is also used to treat severe acne.

Ethinyl estradiol and norethindrone may also be used for other purposes not listed in this medication guide.

What are the possible side effects of ethinyl estradiol and norethindrone?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have any of these serious side effects:
•sudden numbness or weakness, especially on one side of the body;
•sudden headache, confusion, pain behind the eyes, problems with vision, speech, or balance;
•chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; or
•nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:
•mild nausea, vomiting, bloating, stomach cramps;
•breast pain, tenderness, or swelling;
•freckles or darkening of facial skin;
•increased hair growth, loss of scalp hair;
•changes in weight or appetite;
•problems with contact lenses;
•vaginal itching or discharge;
•changes in your menstrual periods, decreased sex drive; or
•headache, nervousness, dizziness.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about ethinyl estradiol and norethindrone?
Do not use birth control pills if you are pregnant or if you have recently had a baby.

Do not use this medication if you have any of the following conditions: a history of stroke or blood clot, circulation problems, a hormone-related cancer such as breast or uterine cancer, abnormal vaginal bleeding, liver disease or liver cancer, or a history of jaundice caused by birth control pills.

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

Taking hormones can increase your risk of blood clots, stroke, or heart attack, especially if you smoke and are older than 35.

Some drugs can make birth control pills less effective, which may result in pregnancy. Tell your doctor about all the prescription and over-the-counter medications you use, including vitamins, minerals and herbal products. Do not start using a new medication without telling your doctor.

What should I discuss with my healthcare provider before taking ethinyl estradiol and norethindrone?
This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills (6 weeks if you are breast-feeding).

Do not use this medication if you have:
•a history of a stroke, blood clot, or circulation problems;
•a hormone-related cancer such as breast or uterine cancer;
•abnormal vaginal bleeding;
•liver disease, liver cancer, or a history of jaundice caused by birth control pills.

Before using this medication, tell your doctor if you have any of the following conditions.
•high blood pressure or a history of heart disease;
•high cholesterol, gallbladder disease, or diabetes;
•migraine headaches or a history of depression; or
•a history of breast cancer or an abnormal mammogram.

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

How should I take ethinyl estradiol and norethindrone?
Take this medication exactly as it was prescribed for you. Do not take larger amounts, or take it for longer than recommended by your doctor. You will take your first pill on the first day of your period or on the first Sunday after your period begins (follow your doctor's instructions).

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

The 28-day birth control pack contains seven "reminder" pills to keep you on your regular cycle. Your period will usually begin while you are using these reminder pills.

You may have breakthrough bleeding, especially during the first 3 months. Tell your doctor if this bleeding continues or is very heavy.

Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. You may get pregnant if you do not use this medication regularly. Get your prescription refilled before you run out of pills completely.

The chewable tablet may be chewed or swallowed whole. If chewed, drink a full glass of water just after you swallow the pill.

If you need to have any type of medical tests or surgery, or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are using birth control pills.

Your doctor will need to see you on a regular basis while you are using this medication. Do not miss any appointments.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?
Missing a pill increases your risk of becoming pregnant.

If you miss one "active" pill, take two pills on the day that you remember. Then take one pill per day for the rest of the pack.

If you miss two "active" pills in a row in week one or two, take two pills per day for two days in a row. Then take one pill per day for the rest of the pack. Use back-up birth control for at least 7 days following the missed pills.

If you miss two "active" pills in a row in week three, or if you miss three pills in a row during any of the first 3 weeks, throw out the rest of the pack and start a new one the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss three "active" pills in a row during any of the first 3 weeks, throw out the rest of the pack and start a new pack on the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss two or more pills, you may not have a period during the month. If you miss a period for two months in a row, call your doctor because you might be pregnant.

If you miss any reminder pills, throw them away and keep taking one pill per day until the pack is empty. You do not need back-up birth control if you miss a reminder pill.

What happens if I overdose?
Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, and vaginal bleeding.

What should I avoid while taking ethinyl estradiol and norethindrone?
Do not smoke while using birth control pills, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills.

Birth control pills will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

What other drugs will affect ethinyl estradiol and norethindrone?
Some drugs can make ethinyl estradiol and norethindrone less effective, which may result in pregnancy. Before using ethinyl estradiol and norethindrone, tell your doctor if you are using any of the following drugs:
•acetaminophen (Tylenol) or ascorbic acid (vitamin C);
•prednisolone (Orapred);
•theophylline (Respbid, Theo-Dur);
•St. John's wort;
•an antibiotic;
•seizure medication;
•a barbiturate sedative such as secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or
•HIV or AIDS medications.

There may be other drugs not listed that can affect this medication. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

---------------------------------------------------------------