Propecia的适应症和用法

保法止®指示用于在MEN ONLY男性型脱发（男性型秃头症）的治疗。

暂时性衰退的功效尚未确定。

不建议将Propecia用于女性。

Propecia剂量和给药

可以将Propecia随餐或不随餐服用。

Propecia的建议剂量是每天一次服用一片（1毫克）。

通常，在观察到益处之前，必须每天使用三个月或更长时间。建议继续使用以维持益处，应定期重新评估。退出治疗会在12个月内逆转疗效。

剂型和优势

Propecia片（1毫克）是棕褐色，八角形，薄膜包衣的凸片，一侧带有“风格化P”徽标，另一侧带有Propecia。

禁忌症

禁忌症有以下禁忌症：

• 怀孕。当女性已经或可能怀孕时，禁忌使用非那雄胺。由于II型5α-还原酶抑制剂具有抑制睾丸激素向5α-二氢睾丸激素（DHT）转化的能力，非那雄胺可能会导致接受非那雄胺的孕妇的男性胎儿的外生殖器异常。如果在怀孕期间使用了该药物，或者在服用该药物时发生了怀孕，则应告知孕妇对男性胎儿的潜在危害。 [请参阅警告和注意事项（5.1） ，在特定人群中使用（8.1） ，如何提供/储存和处理（16）以及患者咨询信息（17.1） 。]在雌性大鼠中，怀孕期间低剂量的非那雄胺产生了异常。雄性后代的外生殖器。
• 对这种药物的任何成分过敏。

警告和注意事项

妇女接触—男性胎儿的风险

不建议将Propecia用于女性。妇女在怀孕时或可能怀孕时，不应处理压碎或破裂的Propecia片剂，因为可能吸收非那雄胺及其后对男性胎儿的潜在危险。 Propecia片剂有涂层，可在正常操作过程中防止与活性成分接触，前提是片剂不得破碎或压碎。 [请参阅适应症和用法（1） ，禁忌症（4） ，在特定人群中的用法（8.1） ，如何提供/存储和处置（16）和患者咨询信息（17.1） 。]

对前列腺特异性抗原（PSA）的影响

在18-41岁的男性中使用Propecia（非那雄胺，1 mg）进行的临床研究中，血清前列腺特异性抗原（PSA）的平均值从基线时的0.7 ng / mL降至第12个月的0.5 ng / mL。在针对患有良性前列腺增生（BPH）的老年男性中使用PROSCAR（非那雄胺，5 mg）的临床研究中，PSA水平降低了约50％。使用PROSCAR进行的其他研究表明，在前列腺癌的存在下，它也可能导致血清PSA降低。在评估使用非那雄胺治疗的男性时，应适当考虑这些发现以正确解释血清PSA。即使在不服用5α-还原酶抑制剂的男性中，即使PSA水平仍在正常范围内，在Propecia上从最低PSA值得到的任何确定的升高都可能预示着前列腺癌的存在，因此应进行评估。不遵守Propecia疗法也可能会影响PSA测试结果。

5α-还原酶抑制剂增加高度前列腺癌的风险

55岁及以上的男性进行了正常的直肠指检并且基线时PSA≤3.0ng / mL，在为期7年的前列腺癌预防试验（PCPT）中服用非那雄胺5 mg /天（是Propecia剂量的5倍）的风险增加Gleason评分8-10的前列腺癌（非那雄胺1.8％vs安慰剂1.1％）。 [请参阅不良反应（6.1） 。 ]在一项为期4年的安慰剂对照临床试验中，使用另一种5α-还原酶抑制剂（dutasteride，AVODART）观察到了相似的结果（1％度他雄胺vs. 0.5％安慰剂）。 5α-还原酶抑制剂可能会增加发生高级前列腺癌的风险。 5α-还原酶抑制剂减少前列腺体积的作用或与研究相关的因素是否影响了这些研究的结果尚未确定。

小儿患者

不建议在儿科患者中使用Propecia [请参见在特定人群中使用（8.4） ] 。

不良反应

临床试验经验

由于临床试验是在广泛不同的条件下进行的，因此不能将在一种药物的临床试验中观察到的不良反应率直接与另一种药物在临床试验中观察到的不良反应率进行比较，并且可能无法反映在临床实践中观察到的不良反应率。

Propecia（非那雄胺1 mg）治疗男性型脱发的临床研究

在为期12个月的Propecia的三项对照临床试验中，因不良反应而被中止的服用Propecia的患者为1.4％（n = 945），被认为可能与药物有关（安慰剂为1.6％； n = 934）。

表1列出了在Propecia或安慰剂治疗的≥1％的患者中据报道可能，可能或绝对与药物相关的临床不良经历。

临床不良经验的综合分析表明，在用Propecia治疗期间，有945名男性中的36名（3.8％）报告了这些不良经历中的一种或多种，​​而用安慰剂治疗的934名男性中有20名（2.1％）（p = 0.04）。由于这些副作用而停止用Propecia治疗的男性和大多数继续治疗的男性，其消退发生了。到了Propecia治疗的第五年，上述每种不良经历的发生率均降至≤0.3％。

在一项针对健康男性每天服用1毫克非那雄胺的研究中，治疗48周后，观察到射精量的中位数减少了0.3毫升（-11％），而安慰剂为0.2毫升（-8％）。另两项研究表明，与安慰剂相比，非那雄胺在Propecia剂量（每天5 mg）的5倍时，射精量的中位数下降显着约0.5 mL（-25％），但这在治疗中断后是可逆的。

在Propecia的临床研究中，非那雄胺治疗的患者的乳房触痛和肿大，超敏反应和睾丸疼痛的发生率与安慰剂治疗的患者无差异。

对照临床试验和长期开放的扩展研究的PROSCAR®（非那雄胺5毫克）和适尿通（度他雄胺）在良性前列腺增生症

在一项为期4年的对照临床研究PROSCAR长期疗效和安全性研究（PLESS）中，对3040例年龄在45至78岁之间有症状BPH和前列腺肥大的患者进行了为期4年的安全性评估（1524年） PROSCAR 5毫克/天，安慰剂1516）。由于与性功能有关的不良反应（最常报告的不良反应）而终止，分别接受3.7％（57例患者）的PROSCAR 5 mg治疗和2.1％（32例患者）的安慰剂治疗终止。

表2列出了研究者认为可能，可能或完全与药物相关的唯一临床不良反应，在研究的4年中，PROSCAR的发生率≥1％，高于安慰剂。在研究的2-4年中，治疗组之间阳imp，性欲降低和射精障碍的发生率无显着差异。

在1年，安慰剂对照，III期BPH研究以及PROSCAR 5 mg和PLESS的5年开放延长中的不良反应情况相似。

没有证据表明使用PROSCAR 5 mg的治疗持续时间增加会增加性不良经历。与药物有关的性不良经历的新报告随着治疗时间的延长而减少。

在一项纳入了3047名男性的4至6年的安慰剂对照药物和比较药物对照的前列腺症状医学治疗（MTOPS）研究中，使用PROSCAR治疗的男性中有4例乳腺癌，但未使用PROSCAR治疗的男性中没有病例。在一项为期30年的3040名男性进行的为期4年的安慰剂对照PLESS研究中，安慰剂治疗的男性有2例乳腺癌，但经PROSCAR治疗的男性没有报道。

在一项为期7年的安慰剂对照前列腺癌预防试验（PCPT）中，该研究招募了18882名男性，其中PROSCAR治疗的男性患者为1例乳腺癌，安慰剂治疗的男性患者为1例乳腺癌。长期使用非那雄胺与男性乳腺肿瘤之间的关系目前尚不清楚。

PCPT试验是一项为期7年的随机，双盲，安慰剂对照试验，纳入了18882名年龄≥55岁的健康男性，其直肠指检正常且PSA≤3.0ng / mL。男性每天接受PROSCAR（非那雄胺5毫克）或安慰剂。每年对患者进行PSA和直肠指检。对PSA升高，直肠指检异常或研究结束进行活检。非那雄胺治疗的男性（1.8％）的格里森评分8-10前列腺癌的发生率高于安慰剂治疗的男性（1.1％）。在一项使用另一种5α-还原酶抑制剂[AVODART（dutasteride）]的为期4年的安慰剂对照临床试验中，格里森评分为8-10的前列腺癌得到了相似的结果（1％度他雄胺vs. 0.5％安慰剂）。这些发现对于男性使用Propecia的临床意义尚不清楚。

在用PROSCAR治疗的前列腺癌患者中未显示出临床益处。未批准PROSCAR降低患前列腺癌的风险。

上市后经验

在Propecia的批准后使用过程中，已经确认了以下不良反应。由于这些反应是从不确定大小的人群中自愿报告的，因此始终无法可靠地估计其发生频率或建立与药物暴露的因果关系：

超敏反应：超敏反应，如皮疹，瘙痒，荨麻疹和血管性水肿（包括嘴唇，舌头，喉咙和面部肿胀）；

生殖系统：性功能障碍在停药后继续存在，包括勃起功能障碍，性欲障碍，射精障碍和性高潮障碍；男性不育和/或精子质量差（已报告非那雄胺停用后精子质量正常化或改善）；睾丸疼痛。 [请参阅不良反应（6.1） 。]

肿瘤：男性乳腺癌；

乳房疾病：乳房压痛和肿大；

神经系统/精神病学：抑郁

药物相互作用

细胞色素P450连锁药物代谢酶系统

尚未发现具有临床重要性的药物相互作用。非那雄胺似乎不影响细胞色素P450连锁的药物代谢酶系统。已在人体中进行测试的化合物包括安替比林，地高辛，心得安，茶碱和华法林，未发现具有临床意义的相互作用。

其他伴随疗法

尽管未进行具体的相互作用研究，但在临床研究中同时使用对乙酰氨基酚，乙酰水杨酸，α-受体阻滞剂，镇痛药，血管紧张素转化酶（ACE）抑制剂，抗惊厥药，苯并二氮杂,、β-受体阻滞剂，钙等1mg或更多的非那雄胺剂量通道阻滞剂，心脏硝酸盐，利尿剂，H 2拮抗剂，HMG-CoA还原酶抑制剂，前列腺素合成酶抑制剂（也称为NSAIDs）和喹诺酮类抗感染药，但无临床上显着不良相互作用的证据。

在特定人群中的使用

怀孕

怀孕类别X [请参阅禁忌症（4） ]。 Propecia禁止用于已怀孕或可能怀孕的妇女。 Propecia是II型5α-还原酶抑制剂，可防止睾丸激素转化为5α-二氢睾丸激素（DHT），这是男性生殖器正常发育所必需的激素。在动物研究中，非那雄胺导致雄性胎儿外生殖器异常发育。如果在怀孕期间使用该药物，或者患者在服用该药物时怀孕，则应告知患者对男性胎儿的潜在危害。

当5α-还原酶抑制剂抑制睾丸激素向5α-二氢睾丸激素（DHT）的转化时，男性生殖器发育异常是预期的结果。这些结果与遗传性5α-还原酶缺乏症的男婴报道的结果相似。通过接触压碎或破裂的Propecia片剂或来自服用Propecia的男性伴侣的精液，女性可能接触非那雄胺。关于非那雄胺经皮肤的暴露，Propecia片剂有涂层，如果片剂没有被压碎或破裂，在正常处理过程中将防止皮肤与非那雄胺接触。怀孕或可能怀孕的妇女不应使用压碎或破裂的Propecia片剂，因为可能会暴露出男性胎儿。如果孕妇接触压碎或破裂的Propecia片剂，应立即用肥皂和水清洗接触部位。关于精液中非那雄胺的潜在暴露，已对接受Propecia 1 mg / day的男性进行了一项研究，该研究测量了精子中非那雄胺的浓度[参见临床药理学（12.3） ]。

在一项胚胎胎儿发育研究中，怀孕的大鼠在主要器官发生期间（妊娠第6至17天）接受了非那雄胺。口服非那雄胺的孕妇剂量约为推荐人剂量（RHD）1 mg /天的1至684倍（基于动物剂量为0.1至100 mg / kg /天的AUC），尿道下裂的剂量依赖性增加是：发生在3.6至100％的雄性后代中。使用非妊娠大鼠的数据估算暴露倍数。妊娠的第16至17天是雄性胎鼠区分外生殖器的关键时期。在口服母体剂量约为RHD的0.2倍（基于动物剂量为0.03 mg / kg /天的AUC）时，雄性后代的前列腺和精囊重量减少，前房分离延迟和短暂的乳头发育。怀孕大鼠雄性后代的肛门生殖器距离降低，RHD约为RHD的0.02倍（基于动物剂量为0.003 mg / kg /天的AUC）。在子宫内暴露于任何剂量的非那雄胺的雌性后代中没有观察到异常。

在未经治疗的雌性与非那雄胺处理的雄性大鼠交配的后代中，未观察到发育异常，RHD约为488倍（基于动物剂量为80 mg / kg / day的AUC）。在妊娠后期和哺乳期给雌性大鼠施用RHD（基于动物剂量为3 mg / kg / day的AUC）的RHD约20倍后，雄性后代的生育力略有下降。在这些条件下，未观察到雌性后代对生育力的影响。

在主要器官发生期间（妊娠第6-18天），母体剂量不超过100 mg / kg / day的非那雄胺暴露的兔子胎儿中，未观察到雄性外生殖器畸形或其他异常的证据（未测定非那雄胺暴露水平）。兔子）。但是，这项研究可能尚未包括非那雄胺对兔子雄性外生殖器发育影响的关键时期。

在恒河猴中（妊娠第20-100天）评估了母体非那雄胺在胚胎和胎儿发育期间的胎儿效应，该物种和发育时期比对大鼠和兔子的研究更能预测人的特异性作用。导致以高达800 ng /天的剂量向怀孕的猴子静脉内施用非那雄胺（估计最大血液浓度为1.86 ng / mL，约为怀孕妇女服用1 mg /天男性精液的非那雄胺最高估计暴露量的930倍）男性胎儿没有异常。为了证实恒河猴模型与人类胎儿发育的相关性，口服非那雄胺剂量（2 mg / kg /天，或服用1 mg /天男性精液的非那雄胺最高估计血液水平的约120,000倍）至怀孕的猴子导致雄性胎儿的外生殖器异常。在任何剂量下，男性胎儿均未观察到其他异常，女性胎儿中未观察到非那雄胺相关的异常。

护理母亲

不建议将Propecia用于女性。

未知非那雄胺是否会在人乳中排出。

儿科用

Propecia不适用于儿科患者。

儿科患者的安全性和有效性尚未确定。

老人用

Propecia的临床疗效研究不包括65岁及以上的受试者。基于非那雄胺5 mg的药代动力学，对于Propecia，老年人无需调整剂量[见临床药理学（12.3） ] 。然而，Propecia在老年人中的功效尚未确立。

肝功能不全

对于那些患有肝功能异常的患者，应谨慎使用Propecia，因为非那雄胺在肝脏中广泛代谢[见临床药理学（12.3） ] 。

肾功能不全

肾功能不全的患者无需调整剂量[见临床药理学（12.3） ] 。

过量

在临床研究中，单剂量的非那雄胺（最高剂量400 mg）和多剂量的非那雄胺（最高剂量80 mg /天）持续三个月都没有引起不良反应。在获得进一步的经验之前，不建议对过量使用非那雄胺进行具体治疗。

在单次口服剂量1500 mg / m 2 （500 mg / kg）的雄性和雌性小鼠中观察到显着的致死性，在单次口服剂量2360 mg / m 2 （400 mg / kg）和5900 mg的雌性和雄性大鼠中观察到显着的致死性/ m 2 （1000 mg / kg）。

规格说明

Propecia（非那雄胺）片剂含有非那雄胺作为有效成分。非那雄胺是一种合成的4-氮杂甾体化合物，是II类固醇5α-还原酶的特异性抑制剂，该酶是一种将雄激素睾丸激素转化为5α-二氢睾丸激素（DHT）的细胞内酶。

非那雄胺的化学名称为N-叔丁基-3-氧代-4-氮杂-5α-雄酮-1-烯-17β-羧酰胺。非那雄胺的经验公式为C 23 H 36 N 2 O 2 ，分子量为372.55。其结构式为：

非那雄胺是白色晶体粉末，熔点接近250°C。它可自由溶于氯仿和低级醇溶剂，但实际上不溶于水。

Propecia（非那雄胺）片剂是用于口服的薄膜包衣片剂。每片含有1毫克非那雄胺和以下非活性成分：乳糖一水合物，微晶纤维素，预胶化淀粉，羟乙酸淀粉钠，羟丙基甲基纤维素，羟丙基纤维素，二氧化钛，硬脂酸镁，滑石粉，多库酯钠，黄色三氧化二铁和红色三价铁氧化物。

Propecia-临床药理学

作用机理

非那雄胺是II型5α-还原酶（一种将雄激素睾丸激素转换成DHT的细胞内酶）的竞争性特异性抑制剂。在小鼠，大鼠，猴子和人类中发现了两种不同的同工酶：I型和II型。这些同工酶均在组织和发育阶段差异表达。在人类中，I型5α还原酶在皮肤的大部分区域（包括头皮和肝脏）的皮脂腺中占主导地位。 I型5α还原酶约占循环DHT的三分之一。 II型5α-还原酶同工酶主要存在于前列腺，精囊，附睾，毛囊和肝脏中，占循环DHT的三分之二。

在人类中，非那雄胺的作用机理是基于其对II型同工酶的优先抑制作用。使用天然组织（头皮和前列腺），体外结合研究检查了非那雄胺抑制两种同工酶的潜力，发现其对人类II型5α-还原酶的选择性是I型同工酶的100倍（IC 50 = 500和4.2 nM对于II型同工酶） I和II）。对于两种同工酶，非那雄胺的抑制作用都伴随着抑制剂还原为二氢非那雄胺和与NADP +形成加合物。酶复合物的周转很慢（II型酶复合物的t 1/2约30天，I型络合物的14天）。 II型5α-还原酶的抑制作用可阻断睾丸激素向DHT的外周转化，从而导致血清和组织DHT浓度显着降低。

在男性脱发（雄激素性脱发）的男性中，与有毛头皮相比，秃顶的头皮包含微型化的毛囊和增加的DHT含量。非那雄胺的施用降低了这些男性的头皮和血清DHT浓度。这些减少对非那雄胺治疗效果的相对贡献尚未确定。通过这种机制，非那雄胺似乎可以打断那些遗传易感患者中雄激素性脱发的关键因素。

药效学

非那雄胺可迅速降低血清DHT浓度，在口服1毫克片剂后24小时内可抑制65％。与基线相比，睾丸激素和雌二醇的平均循环水平增加了约15％，但仍保持在生理范围内。

非那雄胺对雄激素受体没有亲和力，也没有雄激素，抗雄激素，雌激素，抗雌激素或孕育作用。在使用非那雄胺的研究中，未检测到黄体生成激素（LH），促卵泡激素（FSH）或催乳激素的临床意义变化。在健康志愿者中，用非那雄胺治疗不会改变LH和FSH对促性腺激素释放激素的反应，表明下丘脑-垂体-睾丸轴未受影响。非那雄胺对皮质醇，促甲状腺激素或甲状腺素的循环水平没有影响，也没有影响血浆脂质谱（例如总胆固醇，低密度脂蛋白，高密度脂蛋白和甘油三酸酯）或骨矿物质密度。

药代动力学

吸收性

在一项针对15位健康的年轻男性受试者的研究中，基于曲线下面积（AUC）与静脉内（IV）对照的比率，非那雄胺1 mg片剂的平均生物利用度为65％（范围26-170％）剂量。在以1 mg / day（n = 12）给药后达到稳定状态时，非那雄胺的最大血浆浓度平均为9.2 ng / mL（范围4.9-13.7 ng / mL），给药后1至2小时达到最高水平。 AUC （0-24小时）为53 ng∙hr / mL（范围20-154 ng∙hr / mL）。非那雄胺的生物利用度不受食物的影响。

分配

平均稳态分配量为76升（范围为44-96升； n = 15）。大约90％的循环非那雄胺与血浆蛋白结合。多次给药后，非那雄胺有一个缓慢的积累阶段。

已发现非那雄胺可穿过血脑屏障。

已对35名服用非那雄胺1 mg /天，连续6周的男性的精液水平进行了测量。在60％的样本（35个样本中有21个）中，未检测出非那雄胺水平（<0.2 ng / mL）。非那雄胺的平均水平为0.26 ng / mL，测得的最高水平为1.52 ng / mL。使用测得的最高精液水平并假设每天从5mL射精中吸收100％，通过阴道吸收引起的人类暴露量每天将高达7.6 ng，这比非那雄胺剂量（5 µg）少650倍。对男性循环DHT水平没有影响。 [请参阅在特定人群中使用（8.1） 。 ]

代谢

非那雄胺主要通过细胞色素P450 3A4酶亚家族在肝脏中广泛代谢。已经鉴定出两种代谢物，即叔丁基侧链单羟基化和单羧酸代谢物，它们具有非那雄胺的5α-还原酶抑制活性不超过20％。

排泄

在健康的年轻受试者中静脉输注（n = 15）后，非那雄胺的平均血浆清除率为165 mL / min（范围为70-279 mL / min）。血浆中的平均终末半衰期为4.5小时（范围：3.3-13.4小时； n = 12）。在人中口服14 C-非那雄胺后（n = 6），平均39％（范围32-46％）的剂量以代谢产物的形式从尿中排泄出来。 57％（范围为51-64％）从粪便中排出。

18-60岁男性平均终末半衰期约为5-6小时，而70岁以上男性平均终末半衰期约为8小时。

肾功能不全

肾功能不全的患者无需调整剂量。在患有慢性肾功能不全的患者中，肌酐清除率介于9.0至55 mL / min之间，单剂量14 C-非那雄胺后的AUC，最大血浆浓度，半衰期和蛋白质结合与健康志愿者相似。肾功能不全患者尿代谢产物的排泄减少。这种减少与粪便代谢产物的排泄增加有关。肾功能不全患者的血浆代谢物浓度明显更高（基于总放射性AUC增加60％）。但是，在肾功能正常的男性中，以每天80 mg /天的剂量接受非那雄胺治疗12周，据推测这些患者暴露于代谢产物的可能性会更大。

肝功能不全

尚未研究肝功能损害对非那雄胺药代动力学的影响。对于肝功能异常的患者，应谨慎使用Propecia，因为非那雄胺在肝脏中广泛代谢。

非临床毒理学

致癌，诱变，生育力受损

在Sprague-Dawley大鼠的24个月研究中，没有观察到致瘤作用的证据，雄性大鼠接受finasteride的剂量最高为160 mg / kg /天，雌性大鼠接受的finasteride剂量高达320 mg / kg /天。这些剂量在大鼠中产生的全身暴露分别是接受建议的1 mg /天人类剂量的人观察到的888和2192倍。所有暴露量的计算均基于动物的AUC （0-24 hr）和人的平均AUC （0-24 hr） （0.05 µg∙hr / mL）。

在对CD-1小鼠进行的为期19个月的致癌性研究中，在人暴露量（250 mg / kg /天）的1824倍观察到睾丸Leydig细胞腺瘤的发生率具有统计学显着性（p≤0.05）。在估计的人体暴露量184倍（25 mg / kg /天）的小鼠中和在人类暴露量312倍（≥40mg / kg / day）中的大鼠中，莱迪奇细胞增生的发生率增加。在用高剂量非那雄胺治疗的两种啮齿类动物中，均已证明Leydig细胞的增殖变化与血清LH水平升高（比对照高2至3倍）之间呈正相关。在以非那雄胺治疗240次和2800次（分别为20 mg / kg /天和45 mg / kg /天）一年的大鼠或狗中，或在治疗19个月的小鼠中，均未观察到与药物相关的Leydig细胞变化估计为人类暴露的18.4倍（2.5 mg / kg /天）。

在体外细菌诱变测定观察致突变性没有证据，哺乳动物细胞诱变测定中，或在体外碱溶出试验。在体外染色体畸变试验，使用中国仓鼠卵巢细胞，有在染色体畸变略有增加。在小鼠的体内染色体畸变试验，用非那雄胺观察到如在致癌性研究确定250毫克/千克/天的最大耐受剂量（1824倍人曝光）在染色体畸变无治疗相关的增加。

在使用非那雄胺以人类暴露量（80 mg / kg /天）的4344倍治疗长达12周的性成熟雄性兔子中，未观察到对生育力，精子数量或射精量的影响。在经过488倍人体暴露量（80 mg / kg /天）治疗的性成熟雄性大鼠中，治疗6或12周后对生育力没有明显影响；但是，当持续治疗长达24或30周时，生育力，生殖力明显下降，精囊和前列腺的重量也随之显着下降。在停止治疗后6周内，所有这些作用都是可逆的。在大鼠或兔子中，未见到对睾丸或交配性能有药物相关作用。非那雄胺治疗的大鼠的这种生育力下降是继发于其对附属性器官（前列腺和精囊）的影响，从而导致无法形成精囊。精液塞对大鼠正常生育至关重要，但与人无关。

临床研究

男性研究

Propecia的功效在男性（88％的白种人）和18至41岁之间患有中度至中度雄激素性脱发（男性型脱发）的男性中得到了证明。为了防止脂溢性皮炎在这些研究中混淆头发生长的评估，所有男性，无论是否接受非那雄胺或安慰剂治疗，均应在治疗期间使用指定的含药焦油洗发水（Neutrogena T /Gel®洗发水）。前两年的学习。

有三项为期12个月的双盲，随机，安慰剂对照研究。两个主要终点是头发计数和患者自我评估。第二个主要终点是研究者评估和照片评级。此外，还收集了有关性功能（基于自我调查表）和非头皮体毛生长的信息。这三项研究是在1879年对轻度至中度但不完全脱发的男性进行的。其中两项研究招募了以轻度至中度顶点脱发为主的男性（n = 1553）。第三名登记的男性在前中部头皮区域轻度至中度脱发，有或没有顶秃（n = 326）。

男性秃顶研究

在完成两个顶点脱发试验的前12个月的男性中，有1215个选择继续进行安慰剂对照的双盲，12个月延伸研究。共有547名男性接受了Propecia的初始研究和首次扩展期（长达2年的治疗），另有60名男性接受了安慰剂的同期治疗。延长研究继续进行了另外3年，其中有323名接受Propecia治疗的男性和23名接受安慰剂治疗的男性进入了研究的第五年。

为了评估中止治疗的效果，有65名男性在最初的12个月接受了Propecia治疗，然后在延长的头12个月接受了安慰剂治疗。其中一些男性继续进行额外的延伸研究，并转回接受Propecia治疗，其中32名男性进入研究的第五年。最后，在最初的12个月中有543名男性接受了安慰剂，随后在最初的12个月扩展期中接受了Propecia。 Some of these men continued in additional extension studies receiving Propecia, with 290 men entering the fifth year of the study (see Figure 1 below).

Hair counts were assessed by photographic enlargements of a representative area of active hair loss. In these two studies in men with vertex baldness, significant increases in hair count were demonstrated at 6 and 12 months in men treated with Propecia, while significant hair loss from baseline was demonstrated in those treated with placebo. At 12 months there was a 107-hair difference from placebo (p<0.001, Propecia [n=679] vs placebo [n=672]) within a 1-inch diameter circle (5.1 cm 2 ). Hair count was maintained in those men taking Propecia for up to 2 years, resulting in a 138-hair difference between treatment groups (p<0.001, Propecia [n=433] vs placebo [n=47]) within the same area. In men treated with Propecia, the maximum improvement in hair count compared to baseline was achieved during the first 2 years. Although the initial improvement was followed by a slow decline, hair count was maintained above baseline throughout the 5 years of the studies. Furthermore, because the decline in the placebo group was more rapid, the difference between treatment groups also continued to increase throughout the studies, resulting in a 277-hair difference (p<0.001, Propecia [n=219] vs placebo [n=15]) at 5 years (see Figure 1 below).

Patients who switched from placebo to Propecia (n=425) had a decrease in hair count at the end of the initial 12-month placebo period, followed by an increase in hair count after 1 year of treatment with Propecia. This increase in hair count was less (56 hairs above original baseline) than the increase (91 hairs above original baseline) observed after 1 year of treatment in men initially randomized to Propecia. Although the increase in hair count, relative to when therapy was initiated, was comparable between these two groups, a higher absolute hair count was achieved in patients who were started on treatment with Propecia in the initial study. This advantage was maintained through the remaining 3 years of the studies. A change of treatment from Propecia to placebo (n=48) at the end of the initial 12 months resulted in reversal of the increase in hair count 12 months later, at 24 months (see Figure 1 below).

At 12 months, 58% of men in the placebo group had further hair loss (defined as any decrease in hair count from baseline), compared with 14% of men treated with Propecia. In men treated for up to 2 years, 72% of men in the placebo group demonstrated hair loss, compared with 17% of men treated with Propecia. At 5 years, 100% of men in the placebo group demonstrated hair loss, compared with 35% of men treated with Propecia.

图1

Patient self-assessment was obtained at each clinic visit from a self-administered questionnaire, which included questions on their perception of hair growth, hair loss, and appearance. This self-assessment demonstrated an increase in amount of hair, a decrease in hair loss, and improvement in appearance in men treated with Propecia. Overall improvement compared with placebo was seen as early as 3 months (p<0.05), with improvement maintained over 5 years.

Investigator assessment was based on a 7-point scale evaluating increases or decreases in scalp hair at each patient visit. This assessment showed significantly greater increases in hair growth in men treated with Propecia compared with placebo as early as 3 months (p<0.001). At 12 months, the investigators rated 65% of men treated with Propecia as having increased hair growth compared with 37% in the placebo group. At 2 years, the investigators rated 80% of men treated with Propecia as having increased hair growth compared with 47% of men treated with placebo. At 5 years, the investigators rated 77% of men treated with Propecia as having increased hair growth, compared with 15% of men treated with placebo.

An independent panel rated standardized photographs of the head in a blinded fashion based on increases or decreases in scalp hair using the same 7-point scale as the investigator assessment. At 12 months, 48% of men treated with Propecia had an increase as compared with 7% of men treated with placebo. At 2 years, an increase in hair growth was demonstrated in 66% of men treated with Propecia, compared with 7% of men treated with placebo. At 5 years, 48% of men treated with Propecia demonstrated an increase in hair growth, 42% were rated as having no change (no further visible progression of hair loss from baseline) and 10% were rated as having lost hair when compared to baseline. In comparison, 6% of men treated with placebo demonstrated an increase in hair growth, 19% were rated as having no change and 75% were rated as having lost hair when compared to baseline.

A 48-week, placebo-controlled study designed to assess by phototrichogram the effect of Propecia on total and actively growing (anagen) scalp hairs in vertex baldness enrolled 212 men with androgenetic alopecia. At baseline and 48 weeks, total and anagen hair counts were obtained in a 1-cm 2 target area of the scalp. Men treated with Propecia showed increases from baseline in total and anagen hair counts of 7 hairs and 18 hairs, respectively, whereas men treated with placebo had decreases of 10 hairs and 9 hairs, respectively. These changes in hair counts resulted in a between-group difference of 17 hairs in total hair count (p<0.001) and 27 hairs in anagen hair count (p<0.001), and an improvement in the proportion of anagen hairs from 62% at baseline to 68% for men treated with Propecia.

Other Results in Vertex Baldness Studies

A sexual function questionnaire was self-administered by patients participating in the two vertex baldness trials to detect more subtle changes in sexual function. At Month 12, statistically significant differences in favor of placebo were found in 3 of 4 domains (sexual interest, erections, and perception of sexual problems). However, no significant difference was seen in the question on overall satisfaction with sex life.

In one of the two vertex baldness studies, patients were questioned on non-scalp body hair growth. Propecia did not appear to affect non-scalp body hair.

Study in Men with Hair Loss in the Anterior Mid-Scalp Area

A study of 12-month duration, designed to assess the efficacy of Propecia in men with hair loss in the anterior mid-scalp area, also demonstrated significant increases in hair count compared with placebo. Increases in hair count were accompanied by improvements in patient self-assessment, investigator assessment, and ratings based on standardized photographs. Hair counts were obtained in the anterior mid-scalp area, and did not include the area of bitemporal recession or the anterior hairline.

Summary of Clinical Studies in Men

Clinical studies were conducted in men aged 18 to 41 with mild to moderate degrees of androgenetic alopecia. All men treated with Propecia or placebo received a tar-based shampoo (Neutrogena T/Gel® Shampoo) during the first 2 years of the studies. Clinical improvement was seen as early as 3 months in the patients treated with Propecia and led to a net increase in scalp hair count and hair regrowth. In clinical studies for up to 5 years, treatment with Propecia slowed the further progression of hair loss observed in the placebo group. In general, the difference between treatment groups continued to increase throughout the 5 years of the studies.

Ethnic Analysis of Clinical Data from Men

In a combined analysis of the two studies on vertex baldness, mean hair count changes from baseline were 91 vs -19 hairs (Propecia vs placebo) among Caucasians (n=1185), 49 vs -27 hairs among Blacks (n=84), 53 vs -38 hairs among Asians (n=17), 67 vs 5 hairs among Hispanics (n=45) and 67 vs -15 hairs among other ethnic groups (n=20). Patient self-assessment showed improvement across racial groups with Propecia treatment, except for satisfaction of the frontal hairline and vertex in Black men, who were satisfied overall.

Study in Women

In a study involving 137 postmenopausal women with androgenetic alopecia who were treated with Propecia (n=67) or placebo (n=70) for 12 months, effectiveness could not be demonstrated. There was no improvement in hair counts, patient self-assessment, investigator assessment, or ratings of standardized photographs in the women treated with Propecia when compared with the placebo group [see Indications and Usage (1) ] .

供应/存储和处理方式

No. 6642 — Propecia tablets, 1 mg, are tan, octagonal, film-coated convex tablets with "stylized P" logo on one side and Propecia on the other.它们的提供方式如下：

NDC 0006-0071-31 bottles of 30 (with desiccant)

NDC 0006-0071-54 PROPAK ® bottles of 90 (with desiccant).

储存和处理

Store at room temperature, 15-30°C (59-86°F). Keep container closed and protect from moisture.

Women should not handle crushed or broken Propecia tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Propecia tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) and Patient Counseling Information (17.1) ] .

病人咨询信息

See FDA-approved patient labeling (Patient Information) .

Exposure of Women — Risk to Male Fetus

Physicians should inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken Propecia tablets because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Propecia tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. If a woman who is pregnant or may potentially be pregnant comes in contact with crushed or broken Propecia tablets, the contact area should be washed immediately with soap and water [see Contraindications (4) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1) and How Supplied/Storage and Handling (16) ] .

Increased Risk of High-Grade Prostate Cancer

Patients should be informed that there was an increase in high-grade prostate cancer in men treated with 5α-reductase inhibitors indicated for BPH treatment, compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ].

Additional Instructions

Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain or nipple discharge. Breast changes including breast enlargement, tenderness and neoplasm have been reported [see Adverse Reactions (6.1) ] .

Physicians should instruct their patients to read the patient package insert before starting therapy with Propecia and to read it again each time the prescription is renewed so that they are aware of current information for patients regarding Propecia.

距离作者：默克·夏普（Merck Sharp＆Dohme Corp.），
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

有关专利信息：www.merck.com/product/patent/home.html

本文描述的商标归其各自公司所有。

Copyright © 1997 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
版权所有。

uspi-mk0906-1t-1309r011

患者信息
Propecia (Pro-pee-sha)
(finasteride)
平板电脑

Propecia ® is for use by MEN ONLY and should NOT be used by women or children.

Read this Patient Information before you start taking Propecia and each time you get a refill.可能有新的信息。 This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

What is Propecia?

Propecia is a prescription medicine used for the treatment of male pattern hair loss (androgenetic alopecia).

It is not known if Propecia works for a receding hairline on either side of and above your forehead (temporal area).

Propecia is not for use by women and children.

Who should not take Propecia?

Do not take Propecia if you:

• are pregnant or may become pregnant. Propecia may harm your unborn baby.
  • Propecia tablets are coated and will prevent contact with the medicine during handling, as long as the tablets are not broken or crushed. Females who are pregnant or who may become pregnant should not come in contact with broken or crushed Propecia tablets. If a pregnant woman comes in contact with crushed or broken Propecia tablets, wash the contact area right away with soap and water. If a woman who is pregnant comes into contact with the active ingredient in Propecia, a healthcare provider should be consulted.
  • If a woman who is pregnant with a male baby swallows or comes in contact with the medicine in Propecia, the male baby may be born with sex organs that are not normal.
• are allergic to any of the ingredients in Propecia. See the end of this leaflet for a complete list of ingredients in Propecia.

What should I tell my healthcare provider before taking Propecia?

Before taking Propecia, tell your healthcare provider if you:

• have any other medical conditions, including problems with your prostate or liver

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

知道你吃的药。 Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Propecia?

• Take Propecia exactly as your healthcare provider tells you to take it.
• You may take Propecia with or without food.
• If you forget to take Propecia, do not take an extra tablet. Just take the next tablet as usual.

Propecia will not work faster or better if you take it more than once a day.

What are the possible side effects of Propecia?

• decrease in your blood Prostate Specific Antigen (PSA) levels. Propecia can affect a blood test called PSA (Prostate-Specific Antigen) for the screening of prostate cancer. If you have a PSA test done you should tell your healthcare provider that you are taking Propecia because Propecia decreases PSA levels. Changes in PSA levels will need to be evaluated by your healthcare provider. Any increase in follow-up PSA levels from their lowest point may signal the presence of prostate cancer and should be evaluated, even if the test results are still within the normal range for men not taking Propecia. You should also tell your healthcare provider if you have not been taking Propecia as prescribed because this may affect the PSA test results. For more information, talk to your healthcare provider.
• There may be an increased risk of a more serious form of prostate cancer in men taking finasteride at 5 times the dose of Propecia.

The most common side effects of Propecia include:

• decrease in sex drive
• trouble getting or keeping an erection
• a decrease in the amount of semen

The following have been reported in general use with Propecia:

• breast tenderness and enlargement. Tell your healthcare provider about any changes in your breasts such as lumps, pain or nipple discharge.
• 萧条;
• decrease in sex drive that continued after stopping the medication;
• allergic reactions including rash, itching, hives and swelling of the lips, tongue, throat, and face;
• problems with ejaculation that continued after stopping medication;
• testicular pain;
• difficulty in achieving an erection that continued after stopping the medication;
• male infertility and/or poor quality of semen.
• in rare cases, male breast cancer.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Propecia. For more information, ask your healthcare provider or pharmacist.

打电话给您的医生，征求有关副作用的医疗建议。您可以通过1-800-FDA-1088向FDA报告副作用。

How should I store Propecia?

• Store Propecia at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep Propecia in a closed container and keep Propecia tablets dry (protect from moisture).

Keep Propecia and all medicines out of the reach of children.

General information about the safe and effective use of Propecia.

Medicines are sometimes prescribed for purposes other than those listed in this Patient Information leaflet. Do not use Propecia for a condition for which it was not prescribed. Do not give Propecia to other people, even if they have the same symptoms you have.可能会伤害他们。

This Patient Information leaflet summarizes the most important information about Propecia. If you would like more information, talk with yo