度他雄胺胶囊的适应症和用法

单一疗法

Dutasteride胶囊用于治疗前列腺肥大的男性有症状的前列腺增生（BPH）：

•改善症状，

•降低急性尿retention留的风险，以及

•减少需要进行BPH相关手术的风险。

与α肾上腺素能拮抗剂合用

度他雄胺与α-肾上腺素能拮抗剂坦洛新合用，可用于治疗前列腺肥大的男性有症状的BPH。

使用限制

度他雄胺未经批准可用于预防前列腺癌。

度他雄胺胶囊剂量与给药

胶囊应完全吞服且不可咀嚼或打开，因为与胶囊内容物接触可能会刺激口咽粘膜。度他雄胺可以与食物一起或不与食物一起施用。

单一疗法

度他雄胺的推荐剂量为1胶囊（0.5毫克），每天服用一次。

与α肾上腺素能拮抗剂合用

度他雄胺的推荐剂量为1胶囊（0.5毫克），每天一次，坦洛新为0.4毫克，每天一次。

剂型和优势

0.5毫克，黄色，长方形，软明胶胶囊，内含带有黑色墨水印有“ AT131”的透明液体。

禁忌症

度他雄胺禁忌用于：

•怀孕。在动物生殖和发育毒性研究中，度他雄胺抑制雄性胎儿外生殖器的发育。因此，度他雄胺对孕妇给药可能会造成胎儿伤害。如果在怀孕期间使用度他雄胺或如果患者在服用度他雄胺时怀孕，则应告知患者对胎儿的潜在危害[见警告和注意事项（5.4），在特定人群中使用（8.1）] 。

•有生育能力的妇女[见警告和注意事项（5.4），在特定人群中使用（8.1）] 。

•小儿患者[请参见在特定人群中使用（8.4）] 。

•先前表现出对度他雄胺或其他5种α-还原酶抑制剂具有临床上显着的超敏反应（例如，严重的皮肤反应，血管性水肿）的患者[参见不良反应（6.2）] 。

警告和注意事项

对前列腺特异性抗原（PSA）的影响以及PSA在前列腺癌检测中的用途

在临床试验中，度他雄胺在治疗3至6个月内可使血清PSA浓度降低约50％。在有症状BPH的受试者中，这种下降在PSA值的整个范围内都是可以预测的，尽管在个体中可能有所不同。在前列腺癌的存在下，度他雄胺还可能导致血清PSA降低。为了解释服用度他雄胺的男性的连续性PSA，应在开始治疗后至少3个月建立新的PSA基线，然后定期监测PSA。即使在未接受5α-还原酶抑制剂的男性中，即使PSA水平仍在正常范围内，使用度他雄胺时从最低PSA值得到的任何证实的升高都可能表明存在前列腺癌，应进行评估。不符合度他雄胺也可能影响PSA测试结果。

为了解释接受度他雄胺治疗3个月或更长时间的男性的孤立PSA值，应将PSA值加倍以与未经治疗的男性的正常值进行比较。即使在度他雄胺的影响下，总的PSA游离比率（游离PSA百分比）仍保持恒定。如果临床医生选择使用百分比游离PSA辅助检测接受度他雄胺的男性的前列腺癌，则似乎没有必要调整其价值。

与度他雄胺单一疗法合用时，度他雄胺和坦索罗辛对血清PSA的改变相似。

高级别前列腺癌的风险增加

在50到75岁的先前接受过前列腺癌阴性活检且基线PSA在2.5 ng / mL和10.0 ng / mL之间的男性中，在接受dutasteride降低前列腺癌事件（REDUCE）试验的4年中服用dutasteride的患者与服用安慰剂的男性相比，格里森评分为8-10的前列腺癌发生率增加（杜他雄胺1.0％对安慰剂0.5％） [请参阅适应症和用法（1.3），不良反应（6.1）] 。在一项为期7年的安慰剂对照临床试验中，使用另外5种α-还原酶抑制剂（非那雄胺5 mg），格里森评分为8-10的前列腺癌观察到了相似的结果（非那雄胺1.8％对安慰剂1.1％）。

5种α-还原酶抑制剂可能会增加发生高级前列腺癌的风险。 5种α-还原酶抑制剂减少前列腺体积的效果或试验相关因素是否影响这些试验的结果尚未确定。

其他泌尿系统疾病的评估

在开始用度他雄胺治疗之前，应考虑可能引起类似症状的其他泌尿科疾病。此外，BPH和前列腺癌可能并存。

妇女暴露于男性胎儿的风险

怀孕或可能怀孕的妇女不应使用度他雄胺胶囊。度他雄胺可通过皮肤吸收，并可能导致胎儿意外接触。如果怀孕或可能怀孕的妇女接触泄漏的度他雄胺胶囊，则应立即用肥皂和水清洗接触部位[见在特定人群中使用（8.1）] 。

献血

接受度他雄胺治疗的男人在最后一次服药至少六个月后才应献血。该延期的目的是防止向怀孕的女性输血接受者施用度他雄胺。

对精液特性的影响

在整个治疗52周和治疗后24周的随访中，对18至52岁（n = 27 dutasteride，n = 23安慰剂）的正常志愿者评估了0.5 mg / d的度他雄胺对精液特性的影响。调整安慰剂组中的度他雄胺组后，在52周时，度他雄胺组的精子总数，精液量和精子活力较基线平均降低百分比分别为23％，26％和18％。精子浓度和精子形态不受影响。随访24周后，度他雄胺组精子总数的平均变化百分数仍比基线低23％。虽然所有时间点所有精液参数的平均值均保持在正常范围内，不符合临床上显着变化的预定标准（30％），但度他雄胺组中有2名受试者的精子数量减少了90％以上。基线为52周，在24周的随访中部分恢复。度他雄胺对个体患者生育能力对精液特性影响的临床意义尚不清楚。

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，因此无法将在某种药物的临床试验中观察到的不良反应率与在另一种药物的临床试验中观察到的不良反应率直接进行比较，并且可能无法反映实际中观察到的不良反应率。

来自将度他雄胺作为单一疗法或与坦索罗辛联用的临床试验：

•接受度他雄胺治疗的受试者中最常见的不良反应是阳imp，性欲下降，乳房疾病（包括乳房增大和压痛）和射精障碍。在接受联合治疗的受试者（度他雄胺加坦索罗辛）中，最常见的不良反应是阳imp，性欲下降，乳房疾病（包括乳房增大和压痛），射精障碍和头晕。接受联合治疗的受试者（11％）的射精障碍发生率明显高于接受单药单一剂量的度他雄胺（2％）或坦洛新（4％）的受试者。

•在接受度他雄胺的安慰剂对照试验中，有4％的接受度他雄胺的受试者和3％的接受安慰剂的受试者因不良反应而退出试验。导致试验退出的最常见不良反应是阳imp（1％）。

•在评估联合治疗的临床试验中，因不良反应而退出试验的受试者中有6％接受联合疗法（度他雄胺加坦索罗辛），有4％接受度他雄胺或坦索罗辛作为单一疗法。所有治疗组中最常见的不良反应是勃起功能障碍（1％至1.5％），导致试验戒断。

单一疗法：在3个相同的，为期2年的安慰剂对照，双盲，3期治疗试验中，随机分配4300多名BPH男性受试者接受安慰剂或每日0.5 mg的度他雄胺治疗，每项试验随后进行为期2年的标签扩展名。在双盲治疗期间，2,167名男性受试者暴露于度他雄胺，其中1,772人暴露1年，1,510人暴露2年。当包括开放标签扩展名时，将1,009名男性受试者暴露于度他雄胺3年，而812名男性暴露于4年。人口年龄在47至94岁之间（平均年龄：66岁），超过90％是白种人。表1总结了至少有1％接受度他雄胺治疗的受试者的临床不良反应，其发生率高于接受安慰剂的受试者。

表1.在发病后24个月内，在≥1 ％的受试者中报告的不良反应，并且比起安慰剂组（随机，双盲，安慰剂对照试验），接受度他雄胺治疗的组中的不良反应发生率更高

一性，这些不良反应与度他雄胺治疗（包括单一疗法以及组合与坦索罗辛）相关联。这些不良反应可能会在停药后继续存在。度他雄胺在这种持久性中的作用尚不清楚。

b包括乳房压痛和乳房增大。

长期治疗（长达4年）：

高级别前列腺癌： REDUCE试验是一项随机，双盲，安慰剂对照试验，纳入了8,231名年龄在50至75岁之间的男性，血清PSA为2.5 ng / mL至10 ng / mL，前列腺活检阴性前六个月。受试者随机接受安慰剂（N = 4,126）或0.5 mg每日剂量的度他雄胺（N = 4,105），长达4年。平均年龄为63岁，高加索人占91％。如果有临床指征，则在治疗的第2年和第4年对受试者进行协议规定的定期前列腺活检，或者在非定期时间进行“原因活检”。与接受安慰剂的男性（0.5％）相比，接受度他雄胺的男性（1.0％）的格里森得分为8-10的前列腺癌发生率更高[见适应症和用法（1.3），警告和注意事项（5.2）]。在一项为期7年的安慰剂对照临床试验中，使用另外5种α-还原酶抑制剂（非那雄胺5 mg），格里森评分为8-10的前列腺癌观察到了相似的结果（非那雄胺1.8％对安慰剂1.1％）。

在用度他雄胺治疗的前列腺癌患者中未显示出临床益处。

生殖和乳腺疾病：在3个以度他雄胺为基础的安慰剂对照BPH试验中，每持续4年，没有证据表明性不良反应增加（阳pot，性欲降低和射精障碍）或乳腺疾病随着治疗时间的延长而增加。在这3项试验中，度他雄胺组有1例乳腺癌，安慰剂组有1例乳腺癌。在4年CombAT试验或4年REDUCE试验中，任何治疗组均未报告乳腺癌病例。

目前尚不清楚长期使用度他雄胺与男性乳腺肿瘤的关系。

结合α-阻断剂疗法（CombAT） ：随机将超过4,800名患有BPH的男性受试者随机接受0.5 mg dutasteride，0.4 mg tamsulosin或联合疗法（0.5 mg dutasteride加0.4 mg tamsulosin），每天一次。 4年双盲试验。总共1,623名受试者接受了度他雄胺的单一疗法； 1,611名受试者接受坦索罗辛单药治疗； 1,610名受试者接受了联合治疗。人口年龄在49至88岁（平均年龄：66岁），其中88％是白种人。表2总结了在联合治疗组中至少有1％的受试者报告的不良反应，其发生率高于接受度他雄胺或坦索罗辛单一疗法的受试者。

表2.在≥48 ％的时间内，在≥1 ％的受试者中报告的不良反应，并且在联合用药治疗组中比在发作时接受接受度他雄胺或坦索罗辛（CombAT）单药治疗的组更频繁

a组合=度他雄胺0.5毫克，每天一次，加坦洛新0.4毫克，每天一次。

b包括厌食症，逆行射精，精液量减少，性高潮感降低，性高潮异常，射精延迟，射精障碍，射精失败和早泄。

c这些性不良反应与度他雄胺治疗有关（包括单一疗法和坦索罗辛联合用药）。这些不良反应可能会在停药后继续存在。度他雄胺在这种持久性中的作用尚不清楚。

d包括勃起功能障碍和性唤起障碍。

e包括性欲下降，性欲障碍，性欲丧失，性功能障碍和男性性功能障碍。

f包括乳房肿大，女性乳房发育，乳房肿胀，乳房疼痛，乳房压痛，乳头疼痛和乳头肿胀。

心力衰竭：在CombAT中，经过4年的治疗，联合治疗组的复合期心力衰竭的发生率（12 / 1,610; 0.7％）高于任一单药治疗组：度他雄胺2 / 1,623（0.1％）坦洛新为9 / 1,611（0.6％）。在一项单独的为期4年的安慰剂对照试验中也对复合性心力衰竭进行了评估，该试验评估了度他雄胺对有患前列腺癌危险的男性的作用。服用度他雄胺的受试者的心力衰竭发生率为0.6％（26 / 4,105），而使用安慰剂的受试者为0.4％（15 / 4,126）。两项试验中大多数患有心力衰竭的受试者合并症均与心力衰竭的风险增加有关。因此，心力衰竭数值失衡的临床意义尚不清楚。尚未确定单独使用度他雄胺或与坦索罗辛合用与心力衰竭之间的因果关系。在任一试验中，未观察到总体心血管不良事件发生率失衡。

上市后经验

在批准度他雄胺的批准后使用过程中，发现了以下不良反应。由于这些反应是从不确定大小的人群中自愿报告的，因此并非总是能够可靠地估计其发生频率或建立与药物暴露的因果关系。由于这些反应的严重性，报告频率或与度他雄胺的潜在因果关系，因此已选择将这些反应包括在内。

免疫系统疾病：过敏反应，包括皮疹，瘙痒，荨麻疹，局部水肿，严重的皮肤反应和血管性水肿。

肿瘤：男性乳腺癌。

精神疾病：情绪低落。

生殖系统和乳房疾病：睾丸疼痛和睾丸肿胀。

药物相互作用

细胞色素P450 3A抑制剂

度他雄胺通过CYP3A4和CYP3A5同工酶在人体中广泛代谢。尚未研究强效CYP3A4抑制剂对度他雄胺的作用。由于可能存在药物间相互作用，因此在向使用强效，慢性CYP3A4酶抑制剂（例如，利托那韦）的患者开具度他雄胺处方时，应谨慎行事[见临床药理学（12.3）] 。

阿尔法肾上腺素拮抗剂

将度他雄胺与坦索罗辛或特拉唑嗪联用对任何一种α-肾上腺素拮抗剂的稳态药代动力学没有影响。坦索罗辛或特拉唑嗪对度他雄胺药代动力学参数的影响尚未评估。

钙通道拮抗剂

维拉帕米或地尔硫卓的共同给药可降低度他雄胺的清除率，并增加对度他雄胺的暴露。度他雄胺暴露的变化不被认为具有临床意义。建议不调整剂量[见临床药理学（12.3）]。

胆固醇胺

一次服用5 mg的度他雄胺，然后在1小时后再服用12 g的胆甾胺，不会影响度他雄胺的相对生物利用度[见临床药理学（12.3）] 。

地高辛

当以0.5 mg /天的剂量同时给药3周时，度他雄胺不会改变地高辛的稳态药代动力学[见临床药理学（12.3）] 。

华法林

与华法林并用0.5毫克/天的度他雄胺持续3周，不会改变S-或R-华法林异构体的稳态药代动力学，也不会改变华法林对凝血酶原时间的影响[见临床药理学（12.3）] 。

在特定人群中的使用

怀孕

致畸作用

怀孕类别X。度他雄胺是禁忌用于有生育能力的妇女和怀孕期间的妇女。度他雄胺是一种5α-还原酶抑制剂，可防止睾丸激素转化为二氢睾丸激素（DHT），后者是男性生殖器正常发育所必需的激素。在动物生殖和发育毒性研究中，度他雄胺抑制雄性胎儿外生殖器的正常发育。因此，度他雄胺对孕妇给药可能会造成胎儿伤害。如果在怀孕期间使用度他雄胺，或者患者在服用度他雄胺时怀孕，则应告知患者对胎儿的潜在危害。

男性胎儿生殖器异常是5种α-还原酶抑制剂抑制睾丸激素向DHT转化的预期生理结果。这些结果与遗传性5α-还原酶缺乏症的男婴的观察结果相似。度他雄胺是通过皮肤吸收的。为避免潜在的胎儿暴露，已怀孕或可能怀孕的妇女不应使用度他雄胺胶囊。如果与泄漏的胶囊接触，则应立即用肥皂和水清洗接触区域[请参阅警告和注意事项（5.4）] 。度他雄胺被分泌成精液。在接受治疗的男性中，度他雄胺的最高测量精液浓度为14 ng / mL。假设一名50公斤重的妇女暴露于5毫升精液中且吸收率为100％，则该妇女的度他雄胺浓度约为0.0175 ng / mL。该浓度比在动物研究中产生男性生殖器异常的浓度低100倍以上。度他雄胺与人精液中的蛋白质结合度很高（大于96％），这可能会减少可用于阴道吸收的度他雄胺的量。

在雌性大鼠的胚胎-胎儿发育研究中，以每日0.5 mg的最大推荐人类剂量（MRHD）的10倍剂量口服度他雄胺导致胎儿的男性生殖器异常（生殖器距离降低为0.05 mg /公斤/天），乳头发育，尿道下裂和雄性后代的包皮腺扩张（所有剂量分别为0.05、2.5、12.5和30 mg / kg / day）。在MRHD的111倍处观察到死胎的幼崽增加，在MRHD的15倍剂量（动物剂量2.5 mg / kg /天）观察到胎儿体重降低。在MRHD（动物剂量为12.5 mg / kg /天）的约56倍剂量下，观察到被认为是骨化延迟与体重减轻相关的骨骼变异发生率增加。

在兔胚胎胎儿研究中，在主要器官发生期间（妊娠第7至29天），口服MRHD剂量的28-93倍（动物剂量分别为30、100和200 mg / kg /天）。包括外部生殖器发育的后期。胎儿生殖器乳头的组织学评估显示，所有剂量的男性胎儿均女性化。在兔子中进行的第二项胚胎-胎儿研究的预期临床暴露量为动物的0.3-53倍（动物剂量为0.05、0.4、3.0和30 mg / kg / day），也证明雄性胎儿的生殖器全部女性化。剂量。

在大鼠的口服产前和产后发育研究中，度他雄胺的剂量为0.05、2.5、12.5或30 mg / kg /天。雄性后代女性生殖器女性化的明确证据（即，生殖器距离减少，尿道下裂的发生率增加，乳头发育）发生在MRHD（动物剂量为2.5 mg / kg /天或更高）的14到90倍之间。在预期临床暴露量（动物剂量为0.05 mg / kg /天）的0.05倍时，女性化的证据仅限于肛门生殖器距离的缩小，但具有统计学意义。 2.5至30 mg / kg / day的动物剂量导致雌性后代的妊娠时间延长，雌性后代的阴道通畅时间减少，雄性后代的前列腺和精囊重量减少。剂量大于或等于12.5 mg / kg / day时，注意到对新生儿惊吓反应的影响。死产增加，为30 mg / kg / day。

在一项胚胎胎儿发育研究中，将怀孕的恒河猴静脉内暴露于与人类精液中的度他雄胺浓度相当的度他雄胺血药水平。度他雄胺在妊娠第20至100天以400、780、1325或2010 ng /天的剂量（每组12只猴子）给药。猴子后代的男性外生殖器的发育未受到不利影响。在猴子中测试最高剂量时，可以观察到胎儿肾上腺重量的减少，胎儿前列腺重量的减少以及胎儿卵巢和睾丸重量的增加。根据经测量的男性中度他雄胺的最高精液浓度（14 ng / mL），这些剂量代表每天50 mg的女性女性接受度他雄胺治疗的男性5 mL精液的最大潜在暴露量的0.8至16倍吸收百分比。 （这些计算是基于母体药物的血药水平，以母猪每天的ng / kg剂量的32至186倍达到的）。度他雄胺与人精液中的蛋白质高度结合（大于96％），可能会减少可用于阴道吸收的度他雄胺的量。尚不清楚兔子还是恒河猴产生任何主要的人类代谢产物。

将动物研究与度他雄胺的MRHD进行动物研究比较的估计暴露倍数是基于稳态下的临床血清浓度。

护理母亲

度他雄胺是禁忌用于有生育能力的妇女，包括哺乳期妇女。不知道度他雄胺是否会从人乳中排出。

儿科用

Dutasteride禁忌用于儿科患者。儿科患者的安全性和有效性尚未确定。

老人用

在3个临床试验中使用度他雄胺治疗的2167名男性受试者中，有60％的年龄为65岁及以上，另有15％的年龄为75岁及以上。在这些受试者和较年轻的受试者之间未观察到安全性或功效的总体差异。其他已报道的临床经验尚未发现老年患者和年轻患者之间的反应差异，但是不能排除某些老年患者的敏感性更高[见临床药理学（12.3）] 。

肾功能不全

肾功能不全患者中度他雄胺无需调整剂量[见临床药理学（12.3）] 。

肝功能不全

尚未研究肝损害对度他雄胺药代动力学的影响。由于度他雄胺被广泛代谢，因此肝功能不全患者的暴露可能更高。但是，在一项临床试验中，有60名受试者每天接受5 mg（治疗剂量的10倍），持续24周，与0.5 mg治疗剂量观察到的不良事件相比，没有观察到其他不良事件[见临床药理学（12.3）] 。

过量

在志愿者试验中，已服用达40毫克的达他雄胺单次剂量（治疗剂量的80倍），为期7天，没有明显的安全问题。在一项临床试验中，向60位受试者给药5毫克的日剂量（治疗剂量的10倍），持续6个月，与0.5毫克的治疗剂量相比，没有其他副作用。

没有针对度他雄胺的特定解毒剂。因此，在怀疑过量的情况下，应考虑到度他雄胺的半衰期较长，对症下药和支持治疗。

度他雄胺胶囊描述

度他雄胺是一种合成的4-氮杂甾类化合物，是甾类5α-还原酶的1型和2型同工型的选择性抑制剂，甾族5α-还原酶是一种将睾丸激素转化为DHT的细胞内酶。

度他雄胺的化学名称为（5α，17β）-N- {2,5双（三氟甲基）苯基} -3-氧代-4-氮杂杂蒽-1-烯-17-羧酰胺。度他雄胺的经验公式为C 27 H 30 F 6 N 2 O 2 ，其分子量为528.5，具有以下结构式：

度他雄胺为白色至浅黄色粉末，熔点为242°至250°C。它溶于乙醇（44 mg / mL），甲醇（64 mg / mL）和聚乙二醇400（3 mg / mL），但不溶于水。

每个口服度他雄胺胶囊含有溶解在辛酸/癸酸的单二甘油酯和丁基化羟基甲苯的混合物中的0.5 mg的dustasteride。胶囊壳中的惰性赋形剂是三氧化二铁（黄色），明胶（来自经认证的无BSE的牛源），甘油和二氧化钛。胶囊用含有黑色氧化铁，羟丙甲纤维素和丙二醇的食用黑色墨水印刷。

度他雄胺胶囊-临床药理学

作用机理

度他雄胺抑制睾丸激素向二氢睾丸激素（DHT）的转化。 DHT是雄激素，主要负责前列腺的初步发育和随后的扩大。睾丸激素通过5型α-还原酶5型还原酶转化为DHT，它以1型和2型2种亚型存在。2型同工酶主要在生殖组织中起作用，而1型同工酶也负责睾丸激素在生殖组织中的转化。皮肤和肝脏。

度他雄胺是1型和2型5α-还原酶同工酶的竞争性特异性抑制剂，与它形成稳定的酶复合物。已经在体外和体内条件下评估了与该复合物的解离，并且解离非常缓慢。度他雄胺不与人类雄激素受体结合。

药效学

对5种α-二氢睾丸激素和睾丸激素的影响：每日剂量的度他雄胺对DHT降低的最大影响是剂量依赖性的，并且在1-2周内即可观察到。每天服用0.5 mg度他雄胺1和2周后，血清DHT浓度中位数分别降低了85％和90％。在接受0.5 mg / d的度他雄胺治疗4年的BPH患者中，血清DHT的中位降低值在1年时为94％，在2年时为93％，在3和4年时均为95％。血清睾丸激素升高的中位数在1年和2年时均为19％，在3年时为26％，在4年时为22％，但平均水平和中位数水平仍在生理范围内。

在经尿道前列腺电切术之前，接受5 mg /天的度他雄胺或安慰剂治疗的BPH患者长达12周，与安慰剂相比，度他雄胺组前列腺组织中的平均DHT浓度显着降低（784和5,793 pg / g分别为P <0.001）。与安慰剂相比，度他雄胺组的平均前列腺组织睾丸激素浓度显着更高（分别为2073和93 pg / g， P <0.001）。

具有遗传遗传的2 5型α-还原酶缺乏症的成年男性也具有降低的DHT水平。这5位α-还原酶缺陷型男性一生中的前列腺较小，不会发生BPH。除了在出生时出现相关的泌尿生殖器缺陷外，在这些个体中未观察到与5α-还原酶缺乏症相关的其他临床异常。

对其他激素的影响：在健康志愿者中，用度他雄胺0.5 mg /天（n = 26）治疗52周与性安慰剂（n = 23）相比，性激素结合球蛋白，雌二醇，黄体生成激素，促卵泡激素，甲状腺素（游离T4）和脱氢表雄酮。相比于安慰剂，在第8周时的总睾丸激素水平（97.1 ng / dL， P <0.003）和在第52周时的促甲状腺激素（0.4 mcIU / mL， P <0.05）具有统计学意义的基线校正平均升高。度他雄胺组在8周时睾丸激素与基线相比的中位变化百分比为17.9％，在52周时为甲状腺刺激激素的12.4％。停用度他雄胺24周后，在就诊时有可用数据的受试者组中，睾丸激素和促甲状腺激素的平均水平已恢复至基线。在一项大型的随机，双盲，安慰剂对照试验中，用度他雄胺治疗的BPH受试者中，黄体生成激素的中位数百分比升高在6个月时为12％，在12个月和24个月时为19％。

其他影响：在健康志愿者中，每天一次0.5 mg度他雄胺52周后，评估血浆脂质组和骨矿物质密度。与安慰剂或基线相比，通过双能X线吸收法测定的骨矿物质密度没有变化。另外，血浆脂质谱（即总胆固醇，低密度脂蛋白，高密度脂蛋白和甘油三酸酯）不受度他雄胺影响。在为期1年的健康志愿者试验的一个子集人群（n = 13）中，未观察到肾上腺激素对促肾上腺皮质激素（ACTH）刺激的临床显着变化。

药代动力学

吸收：每次服用0.5毫克的胶囊后，达他雄酯的血清浓度峰值（T max ）会在2至3个小时内出现。 5名健康受试者的绝对生物利用度约为60％（范围：40％至94％）。与食物一起给药时，最大血清浓度降低了10％至15％。这种减少没有临床意义。

分布：单次和重复口服剂量后的药代动力学数据表明，度他雄胺分布较大（300至500 L）。度他雄胺与血浆白蛋白（99.0％）和α-1酸性糖蛋白（96.6％）高度结合。

在一项健康受试者（n = 26）的试验中，每天接受0.5 mg的度他雄胺12个月，在12个月时平均度他雄胺精液浓度为3.4 ng / mL（范围：0.4至14 ng / mL），并且与血清相似，达到了稳定水平状态浓度为6个月。平均而言，在12个月时，血清dutasteride浓度的11.5％分为精液。

代谢和消除：度他雄胺在人体中广泛代谢。体外研究表明，度他雄胺被CYP3A4和CYP3A5同工酶代谢。这两种同工酶均产生4'-羟基杜仲酯，6-羟基杜仲酯和6,4'-二羟基杜仲酯代谢产物。此外，由CYP3A4形成15-羟基十二碳六烯酸酯。度他雄胺在体外不会被人细胞色素P450同工酶CYP1A2，CYP2A6，CYP2B6，CYP2C8，CYP2C9，CYP2C19，CYP2D6和CYP2E1代谢。在达到稳态后的人血清中，度他雄胺，3种主要代谢物（4'-羟基杜他甾酯，1,2-二氢杜他甾酯和6-羟基杜他甾酯）和2种次要代谢物（6,4'-二羟基杜他甾酯和15-羟基杜他甾酯），经质谱响应评估，已被检测到。 The absolute stereochemistry of the hydroxyl additions in the 6 and 15 positions is not known. In vitro, the 4′-hydroxydutasteride and 1,2-dihydrodutasteride metabolites are much less potent than dutasteride against both isoforms of human 5 alpha-reductase. The activity of 6β-hydroxydutasteride is comparable to that of dutasteride.

Dutasteride and its metabolites were excreted mainly in feces. As a percent of dose, there was approximately 5% unchanged dutasteride (~1% to ~15%) and 40% as dutasteride-related metabolites (~2% to ~90%). Only trace amounts of unchanged dutasteride were found in urine (<1%). Therefore, on average, the dose unaccounted for approximated 55% (range: 5% to 97%).

The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. The average steady-state serum dutasteride concentration was 40 ng/mL following 0.5 mg/day for 1 year. Following daily dosing, dutasteride serum concentrations achieve 65% of steady-state concentration after 1 month and approximately 90% after 3 months. Due to the long half-life of dutasteride, serum concentrations remain detectable (greater than 0.1 ng/mL) for up to 4 to 6 months after discontinuation of treatment.

特定人群：

Pediatric: Dutasteride pharmacokinetics have not been investigated in subjects younger than 18 years.

Geriatric: No dose adjustment is necessary in the elderly. The pharmacokinetics and pharmacodynamics of dutasteride were evaluated in 36 healthy male subjects aged between 24 and 87 years following administration of a single 5-mg dose of dutasteride. In this single-dose trial, dutasteride half-life increased with age (approximately 170 hours in men aged 20 to 49 years, approximately 260 hours in men aged 50 to 69 years, and approximately 300 hours in men older than 70 years). Of 2,167 men treated with dutasteride in the 3 pivotal trials, 60% were age 65 and over and 15% were age 75 and over.在这些患者和年轻患者之间未观察到安全性或疗效的总体差异。

Gender: Dutasteride is contraindicated in pregnancy and women of childbearing potential and is not indicated for use in other women [see Contraindications (4), Warnings and Precautions (5.1)] . The pharmacokinetics of dutasteride in women have not been studied.

Race : The effect of race on dutasteride pharmacokinetics has not been studied.

Renal Impairment : The effect of renal impairment on dutasteride pharmacokinetics has not been studied. However, less than 0.1% of a steady-state 0.5-mg dose of dutasteride is recovered in human urine, so no adjustment in dosage is anticipated for patients with renal impairment.

Hepatic Impairment : The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients.

Drug Interactions :

Cytochrome P450 Inhibitors : No clinical drug interaction trials have been performed to evaluate the impact of CYP3A enzyme inhibitors on dutasteride pharmacokinetics. However, based on in vitro data, blood concentrations of dutasteride may increase in the presence of inhibitors of CYP3A4/5 such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin.

Dutasteride does not inhibit the in vitro metabolism of model substrates for the major human cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at a concentration of 1,000 ng/mL, 25 times greater than steady-state serum concentrations in humans.

Alpha Adrenergic Antagonists : In a single-sequence, crossover trial in healthy volunteers, the administration of tamsulosin or terazosin in combination with dutasteride had no effect on the steady-state pharmacokinetics of either alpha adrenergic antagonist. Although the effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters was not evaluated, the percent change in DHT concentrations was similar for dutasteride alone compared with the combination treatment.

Calcium Channel Antagonists : In a population pharmacokinetics analysis, a decrease in clearance of dutasteride was noted when coadministered with the CYP3A4 inhibitors verapamil (-37%, n = 6) and diltiazem (-44%, n = 5). In contrast, no decrease in clearance was seen when amlodipine, another calcium channel antagonist that is not a CYP3A4 inhibitor, was coadministered with dutasteride (+7%, n = 4).

The decrease in clearance and subsequent increase in exposure to dutasteride in the presence of verapamil and diltiazem is not considered to be clinically significant. No dose adjustment is recommended.

Cholestyramine: Administration of a single 5-mg dose of dutasteride followed 1 hour later by 12 g cholestyramine did not affect the relative bioavailability of dutasteride in 12 normal volunteers.

Digoxin : In a trial of 20 healthy volunteers, dutasteride did not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks.

Warfarin: In a trial of 23 healthy volunteers, 3 weeks of treatment with dutasteride 0.5 mg/day did not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time when administered with warfarin.

Other Concomitant Therapy: Although specific interaction trials were not performed with other compounds, approximately 90% of the subjects in the 3 randomized, double-blind, placebo-controlled safety and efficacy trials receiving dutasteride were taking other medications concomitantly. No clinically significant adverse interactions could be attributed to the combination of dutasteride and concurrent therapy when dutasteride was coadministered with anti-hyperlipidemics, angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic blocking agents, calcium channel blockers, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), phosphodiesterase Type V inhibitors, and quinolone antibiotics.

非临床毒理学

致癌，诱变，生育力受损

Carcinogenesis : A 2-year carcinogenicity study was conducted in B6C3F1 mice at doses of 3, 35, 250, and 500 mg/kg/day for males and 3, 35, and 250 mg/kg/day for females; an increased incidence of benign hepatocellular adenomas was noted at 250 mg/kg/day (290-fold the MRHD of a 0.5-mg daily dose) in female mice only. Two of the 3 major human metabolites have been detected in mice. The exposure to these metabolites in mice is either lower than in humans or is not known.

In a 2-year carcinogenicity study in Han Wistar rats, at doses of 1.5, 7.5, and 53 mg/kg/day in males and 0.8, 6.3, and 15 mg/kg/day in females, there was an increase in Leydig cell adenomas in the testes at 135-fold the MRHD (53 mg/kg/day and greater). An increased incidence of Leydig cell hyperplasia was present at 52-fold the MRHD (male rat doses of 7.5 mg/kg/day and greater). A positive correlation between proliferative changes in the Leydig cells and an increase in circulating luteinizing hormone levels has been demonstrated with 5 alpha-reductase inhibitors and is consistent with an effect on the hypothalamic-pituitary-testicular axis following 5 alpha-reductase inhibition. At tumorigenic doses, luteinizing hormone levels in rats were increased by 167%. In this study, the major human metabolites were tested for carcinogenicity at approximately 1 to 3 times the expected clinical exposure.

Mutagenesis : Dutasteride was tested for genotoxicity in a bacterial mutagenesis assay (Ames test), a chromosomal aberration assay in CHO cells, and a micronucleus assay in rats. The results did not indicate any genotoxic potential of the parent drug. Two major human metabolites were also negative in either the Ames test or an abbreviated Ames test.

Impairment of Fertility : Treatment of sexually mature male rats with dutasteride at 0.1- to 110-fold the MRHD (animal doses of 0.05, 10, 50, and 500 mg/kg/day for up to 31 weeks) resulted in dose- and time-dependent decreases in fertility; reduced cauda epididymal (absolute) sperm counts but not sperm concentration (at 50 and 500 mg/kg/day); reduced weights of the epididymis, prostate, and seminal vesicles; and microscopic changes in the male reproductive organs. The fertility effects were reversed by recovery week 6 at all doses, and sperm counts were normal at the end of a 14-week recovery period. The 5 alpha-reductase–related changes consisted of cytoplasmic vacuolation of tubular epithelium in the epididymides and decreased cytoplasmic content of epithelium, consistent with decreased secretory activity in the prostate and seminal vesicles. The microscopic changes were no longer present at recovery week 14 in the low-dose group and were partly recovered in the remaining treatment groups. Low levels of dutasteride (0.6 to 17 ng/mL) were detected in the serum of untreated female rats mated to males dosed at 10, 50, or 500 mg/kg/day for 29 to 30 weeks.

In a fertility study in female rats, oral administration of dutasteride at doses of 0.05, 2.5, 12.5, and 30 mg/kg/day resulted in reduced litter size, increased embryo resorption, and feminization of male fetuses (decreased anogenital distance) at 2- to 10-fold the MRHD (animal doses of 2.5 mg/kg/day or greater). Fetal body weights were also reduced at less than 0.02-fold the MRHD in rats (0.5 mg/kg/day).

动物毒理学和/或药理学

Central Nervous System Toxicology Studies: In rats and dogs, repeated oral administration of dutasteride resulted in some animals showing signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes at exposures 425- and 315-fold the expected clinical exposure (of parent drug), respectively.

临床研究

Monotherapy

Dutasteride 0.5 mg/day (n = 2,167) or placebo (n = 2,158) was evaluated in male subjects with BPH in three 2-year multicenter, placebo-controlled, double-blind trials, each with 2-year open-label extensions (n = 2,340). More than 90% of the trial population was Caucasian. Subjects were at least 50 years of age with a serum PSA ≥1.5 ng/mL and <10 ng/mL and BPH diagnosed by medical history and physical examination, including enlarged prostate (≥30 cc) and BPH symptoms that were moderate to severe according to the American Urological Association Symptom Index (AUA-SI). Most of the 4,325 subjects randomly assigned to receive either dutasteride or placebo completed 2 years of double-blind treatment (70% and 67%, respectively). Most of the 2,340 subjects in the trial extensions completed 2 additional years of open-label treatment (71%).

Effect on Symptom Scores: Symptoms were quantified using the AUA-SI, a questionnaire that evaluates urinary symptoms (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) by rating on a 0 to 5 scale for a total possible score of 35, with higher numerical total symptom scores representing greater severity of symptoms. The baseline AUA-SI score across the 3 trials was approximately 17 units in both treatment groups.

Subjects receiving dutasteride achieved statistically significant improvement in symptoms versus placebo by Month 3 in 1 trial and by Month 12 in the other 2 pivotal trials. At Month 12, the mean decrease from baseline in AUA-SI total symptom scores across the 3 trials pooled was -3.3 units for dutasteride and -2.0 units for placebo with a mean difference between the 2 treatment groups of -1.3 (range: -1.1 to -1.5 units in each of the 3 trials, P <0.001) and was consistent across the 3 trials. At Month 24, the mean decrease from baseline was -3.8 units for dutasteride and -1.7 units for placebo with a mean difference of -2.1 (range: -1.9 to -2.2 units in each of the 3 trials, P <0.001). See Figure 1. The improvement in BPH symptoms seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

These trials were prospectively designed to evaluate effects on symptoms based on prostate size at baseline. In men with prostate volumes ≥40 cc, the mean decrease was -3.8 units for dutasteride and -1.6 units for placebo, with a mean difference between the 2 treatment groups of -2.2 at Month 24. In men with prostate volumes <40 cc, the mean decrease was -3.7 units for dutasteride and -2.2 units for placebo, with a mean difference between the 2 treatment groups of -1.5 at Month 24.

Figure 1. AUA-SI Score a Change From Baseline (Randomized, Double-Blind, Placebo- Controlled Trials Pooled)

a AUA-SI score ranges from 0 to 35.

Effect on Acute Urinary Retention and the Need for BPH-Related Surgery: Efficacy was also assessed after 2 years of treatment by the incidence of AUR requiring catheterization and BPH-related urological surgical intervention. Compared with placebo, dutasteride was associated with a statistically significantly lower incidence of AUR (1.8% for dutasteride versus 4.2% for placebo, P <0.001; 57% reduction in risk, [95% CI: 38% to 71%]) and with a statistically significantly lower incidence of surgery (2.2% for dutasteride versus 4.1% for placebo, P <0.001; 48% reduction in risk, [95% CI: 26% to 63%]). See Figures 2 and 3.

Figure 2. Percent of Subjects Developing Acute Urinary Retention Over a 24-Month Period (Randomized, Double-Blind, Placebo-Controlled Trials Pooled)

Figure 3. Percent of Subjects Having Surgery for Benign Prostatic Hyperplasia Over a 24-Month Period (Randomized, Double-Blind, Placebo-Controlled Trials Pooled)

Effect on Prostate Volume: A prostate volume of at least 30 cc measured by transrectal ultrasound was required for trial entry. The mean prostate volume at trial entry was approximately 54 cc.

Statistically significant differences (dutasteride versus placebo) were noted at the earliest post-treatment prostate volume measurement in each trial (Month 1, Month 3, or Month 6) and continued through Month 24. At Month 12, the mean percent change in prostate volume across the 3 trials pooled was -24.7% for dutasteride and -3.4% for placebo; the mean difference (dutasteride minus placebo) was -21.3% (range: -21.0% to -21.6% in each of the 3 trials, P <0.001). At Month 24, the mean percent change in prostate volume across the 3 trials pooled was -26.7% for dutasteride and -2.2% for placebo with a mean difference of -24.5% (range: -24.0% to -25.1% in each of the 3 trials, P <0.001). See Figure 4. The reduction in prostate volume seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

Figure 4. Prostate Volume Percent Change From Baseline (Randomized, Double-Blind, Placebo-Controlled Trials Pooled)

Effect on Maximum Urine Flow Rate: A mean peak urine flow rate (Q max ) of ≤15 mL/sec was required for trial entry. Q max was approximately 10 mL/sec at baseline across the 3 pivotal trials.

Differences between the 2 groups were statistically significant from baseline at Month 3 in all 3 trials and were maintained through Month 12. At Month 12, the mean increase in Q max across the 3 trials pooled was 1.6 mL/sec for dutasteride and 0.7 mL/sec for placebo; the mean difference (dutasteride minus placebo) was 0.8 mL/sec (range: 0.7 to 1.0 mL/sec in each of the 3 trials, P <0.001). At Month 24, the mean increase in Q max was 1.8 mL/sec for dutasteride and 0.7 mL/sec for placebo, with a mean difference of 1.1 mL/sec (range: 1.0 to 1.2 mL/sec in each of the 3 trials, P <0.001). See Figure 5. The increase in maximum urine flow rate seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

Figure 5. Q max Change From Baseline (Randomized, Double-Blind, Placebo-Controlled Trials Pooled)

Summary of Clinical Trials : Data from 3 large, well-controlled efficacy trials demonstrate that treatment with dutasteride (0.5 mg once daily) reduces the risk of both AUR and BPH-related surgical intervention relative to placebo, improves BPH-related symptoms, decreases prostate volume, and increases maximum urinary flow rates. These data suggest that dutasteride arrests the disease process of BPH in men with an enlarged prostate.

Combination With Alpha-Blocker Therapy (CombAT)

The efficacy of combination therapy (dutasteride 0.5 mg/day plus tamsulosin 0.4 mg/day, n = 1,610) was compared with dutasteride alone (n = 1,623) or tamsulosin alone (n = 1,611) in a 4-year multicenter, randomized, double-blind trial. Trial entry criteria were similar to the double-blind, placebo-controlled monotherapy efficacy trials described above in section 14.1. Eighty-eight percent (88%) of the enrolled trial population was Caucasian. Approximately 52% of subjects had previous exposure to 5 alpha-reductase inhibitor or alpha adrenergic antagonist treatment. Of the 4,844 subjects randomly assigned to receive treatment, 69% of subjects in the combination group, 67% in the group receiving dutasteride, and 61% in the tamsulosin group completed 4 years of double-blind treatment.

Effect on Symptom Score: Symptoms were quantified using the first 7 questions of the International Prostate Symptom Score (IPSS) (identical to the AUA-SI). The baseline score was approximately 16.4 units for each treatment group. Combination therapy was statistically superior to each of the monotherapy treatments in decreasing symptom score at Month 24, the primary time point for this endpoint. At Month 24 the mean changes from baseline (±SD) in IPSS total symptom scores were -6.2 (±7.14) for combination, -4.9 (±6.81) for dutasteride, and -4.3 (±7.01) for tamsulosin, with a mean difference between combination and dutasteride of -1.3 units ( P <0.001; [95% CI: -1.69, -0.86]), and between combination and tamsulosin of -1.8 units ( P <0.001; [95% CI: -2.23, -1.40]). A significant difference was seen by Month 9 and continued through Month 48. At Month 48 the mean changes from baseline (±SD) in IPSS total symptom scores were -6.3 (±7.40) for combination, -5.3 (±7.14) for dutasteride, and -3.8 (±7.74) for tamsulosin, with a mean difference between combination and dutasteride of -0.96 units ( P <0.001; [95% CI: -1.40, -0.52]), and between combination and tamsulosin of -2.5 units ( P <0.001; [95% CI: -2.96, -2.07]). See Figure 6.

Figure 6. International Prostate Symptom Score Change From Baseline Over a 48-Month Period (Randomized, Double-Blind, Parallel Group Trial [CombAT Trial])

Effect on Acute Urinary Retention or the Need for BPH-Related Surgery: After 4 years of treatment, combination therapy with dutasteride and tamsulosin did not provide benefit over monotherapy with dutasteride in reducing the incidence of AUR or BPH-related surgery.

Effect on Maximum Urine Flow Rate: The baseline Q max was approximately 10.7 mL/sec for each treatment group. Combination therapy was statistically superior to each of the monotherapy treatments in increasing Q max at Month 24, the primary time point for this endpoint. At Month 24, the mean increases from baseline (±SD) in Q max were 2.4 (±5.26) mL/sec for combination, 1.9 (±5.10) mL/sec for dutasteride, and 0.9 (±4.57) mL/sec for tamsulosin, with a mean difference between combination and dutasteride of 0.5 mL/sec ( P = 0.003; [95% CI: 0.17, 0.84]), and between combination and tamsulosin of 1.5 mL/sec ( P <0.001; [95% CI: 1.19, 1.86]). This difference was seen by Month 6 and continued through Month 24. See Figure 7.

The additional improvement in Q max of combination therapy over monotherapy with dutasteride was no longer statistically significant at Month 48.

Figure 7. Q max Change From Baseline Over a 24-Month Period (Randomized, Double-Blind, Parallel Group Trial [CombAT Trial])

Effect on Prostate Volume : The mean prostate volume at trial entry was approximately 55 cc. At Month 24, the primary time point for this endpoint, the mean percent changes from baseline (±SD) in prostate volume were -26.9% (±22.57) for combination therapy, -28.0% (±24.88) for dutasteride, and 0% (±31.14) for tamsulosin, with a mean difference between combination and dutasteride of 1.1% ( P = NS; [95% CI: -0.6, 2.8]), and between combination and tamsulosin of -26.9% ( P <0.001; [95% CI: -28.9, -24.9]). Similar changes were seen at Month 48: -27.3% (±24.91) for combination therapy, -28.0% (±25.74) for dutasteride, and +4.6% (±35.45) for tamsulosin.

供应/存储和处理方式

Dutasteride Capsules 0.5 mg are yellow, oblong capsules containing clear liquid printed with 'AT131' with black ink, packaged in bottles of 30 (NDC 72865-140-30) and 90 (NDC 72865-140-90) with child-resistant closures.

存放在20°至25°C（68°至77°F）。 [请参见USP控制的室温]。

Dutasteride is absorbed through the skin. Dutasteride Capsules should not be handled by women who are pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus [see Warnings and Precautions (5.4)] .

病人咨询信息

See FDA-approved patient labeling (Patient Information).

PSA Monitoring

Physicians should inform patients that dutasteride reduces serum PSA levels by approximately 50% within 3 to 6 months of therapy, although it may vary for each individual. For patients undergoing PSA screening, increases in PSA levels while on treatment with dutasteride may signal the presence of prostate cancer and should be evaluated by a healthcare provider [see Warnings and Precautions (5.1)] .

Increased Risk of High-Grade Prostate Cancer

Physicians should inform patients that there was an increase in high-grade prostate cancer in men treated with 5 alpha-reductase inhibitors (which are indicated for BPH treatment), including dutasteride, compared with those treated with placebo in trials looking at the use of these drugs to reduce the risk of prostate cancer [see Indications and Usage (1.3), Warnings and Precautions (5.2), Adverse Reactions (6.1)] .

Exposure of Women—Risk to Male Fetus

Physicians should inform patients that Dutasteride Capsules should not be handled by a woman who is pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus. Dutasteride is absorbed through the skin and could result in unintended fetal exposure. If a pregnant woman or woman of childbearing potential comes in contact with leaking Dutasteride Capsules, the contact area should be washed immediately with soap and water [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] .

Blood Donation

Physicians should inform men treated with dutasteride that they should not donate blood until at least 6 months following their last dose to prevent pregnant women from receiving dutasteride through blood transfusion [see Warnings and Precautions (5.5)] . Serum levels of dutasteride are detectable for 4 to 6 months after treatment ends [see Clinical Pharmacology (12.3)] .

由制造：

Ascent Pharmaceuticals, Inc.

Central Islip, NY 11722

制造用于：

XLCare Pharmaceuticals, Inc.

242 South Culver Street, Suite 202

Lawrenceville, GA 30046

Rev: 03/20

患者信息

Dutasteride Capsules

(doo tas' ter ide)

Dutasteride Capsules are for use by men only.

Read this patient information before you start taking dutasteride and each time you get a refill.可能有新的信息。此信息不能代替您与医疗保健提供者讨论您的医疗状况或治疗方法。

What is Dutasteride?

Dutasteride Capsules are a prescription medicine that contains dutasteride. Dutasteride is used to treat the symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:

• improve symptoms
• reduce the risk of acute urinary retention (a complete blockage of urine flow)
• reduce the risk of the need for BPH-related surgery

Who should NOT take Dutasteride Capsules?

Do Not Take Dutasteride Capsules if you are:

• pregnant or could become pregnant. Dutasteride Capsules may harm your unborn baby. Pregnant women should not touch Dutasteride Capsules. If a woman who is pregnant with a male baby gets enough dutasteride in her body by swallowing or touching dutasteride, the male baby may be born with sex organs that are not normal. If a pregnant woman or woman of childbearing potential comes in contact with leaking Dutasteride Capsules, the contact area should be washed immediately with soap and water.
• a child or a teenager.
• allergic to dutasteride or any of the ingredients in Dutasteride Capsules. See the end of this leaflet for a complete list of ingredients in Dutasteride Capsules.
• allergic to other 5 alpha-reductase inhibitors, for example, finasteride tablets.

What should I tell my healthcare provider before taking Dutasteride Capsules?

对于消费者

适用于度他雄胺：口服胶囊液体填充

需要立即就医的副作用

除其需要的作用外，度他雄胺可能会引起一些不良作用。尽管并非所有这些副作用都可能发生，但如果确实发生了，则可能需要医疗护理。

服用度他雄胺时，如果有下列任何副作用，请立即与医生联系：

罕见

• 胸痛或不适
• 颈静脉扩张
• 极度疲劳
• 不规则的呼吸
• 心律不齐
• 气促
• 面部，手指，脚或小腿肿胀
• 体重增加
• 喘息

发病率未知

• 皮肤起泡，剥落或脱皮
• 咳嗽
• 吞咽困难
• 头晕
• 快速的心跳
• 荨麻疹
• 皮肤瘙痒
• 面部，眼睑，嘴唇，舌头，喉咙，手，腿，脚或性器官上的大型蜂巢状肿胀
• 眼睑或眼睛，面部，嘴唇或舌头周围浮肿或肿胀
• 皮肤发红
• 皮疹
• 胸闷
• 异常疲倦或虚弱
• 喘息

不需要立即就医的副作用

度他雄胺可能会出现一些副作用，这些副作用通常不需要医疗。随着身体对药物的适应，这些副作用可能会在治疗期间消失。另外，您的医疗保健专业人员可能会告诉您一些预防或减少这些副作用的方法。

请咨询您的医疗保健专业人员，是否持续存在以下不良反应或令人讨厌，或者是否对这些副作用有任何疑问：

不常见

• 射精异常
• 对性交的兴趣减少
• 性能力或性欲下降
• 阳
• 无法勃起或勃起
• 性能力，欲望，动力或表现丧失
• 乳房疼痛，酸痛，肿胀或分泌物

对于医疗保健专业人员

适用于度他雄胺：口服胶囊

其他

常见（1％至10％）：阳ence，性欲下降，射精障碍，乳腺疾病

上市后报道：睾丸疼痛和肿胀^[参考]

-停止治疗后，阳I，性欲降低和射精障碍可能会持续；这种药物在这种持久性中的作用尚不清楚。

-射精障碍包括性欲减退，射精逆行，精液量减少，性高潮感减少，性高潮异常，射精延迟，射精失败和早泄。

-乳房疾病包括乳房肿大，女性乳房发育，乳房肿胀，乳房疼痛，乳房压痛，乳头疼痛和乳头肿胀。 ^[参考]

肿瘤的

常见（1％至10％）：高度前列腺癌

未报告频率：男性乳腺癌^[参考]

心血管的

罕见（0.1％至1％）：心脏衰竭^[参考]

皮肤科

罕见（0.1％至1％）：脱发（主要是脱发），高发症^[参考]

神经系统

罕见（0.1％至1％）：头晕，神经系统疾病^[参考]

过敏症

上市后报告：过敏反应（例如皮疹，瘙痒，荨麻疹，局部水肿，严重的皮肤反应，血管性水肿） ^[参考]

精神科

上市后报告：情绪低落^[参考]

某些副作用可能没有报道。您可以将其报告给FDA。

良性前列腺增生的通常成人剂量

每天一次口服0.5 mg

使用：治疗前列腺肥大的男性症状性前列腺增生症（BPH），以减少急性尿acute留（AUR）和与BPH相关的手术的风险。

肾脏剂量调整

不建议调整。

肝剂量调整

由于该药物被广泛代谢，肝功能不全患者的药物暴露可能更高，因此可能需要调整剂量。但是，没有建议任何具体的准则。建议注意。

预防措施

未确定18岁以下患者的安全性和疗效。

有关其他预防措施，请参阅“警告”部分。

透析

数据不可用。

其他的建议

行政建议：
-该药物可以随食物一起服用或不随食物服用。
-药物胶囊应完全吞服，请勿咀嚼或打开，因为与胶囊内容物接触可能会刺激口咽粘膜。

一般：
-该药物未获批准用于预防前列腺癌。
-可能需要长达6个月的时间才能达到对该药物的治疗效果。
-停止治疗后4到6个月可检测到该药物的血清水平。
-使用5种α-还原酶抑制剂可能会减少男性型患者的脱发并诱导其头发生长。
-过量：没有特定的解毒剂；应适当给予对症和支持治疗，并应考虑该药物的长半衰期。

监控：
肿瘤科：新的PSA基线（治疗3个月后）；直肠指检和PSA测试（在治疗期间定期进行）