英文药名：Daklinza(Daclatasvir Tablets) 中文药名：达卡他韦片 生产厂家：Bristol-Myers Squibb Company 药品介绍 Daklinza（daclatasvir）用于联合Sovaldi（sofosbuvir，索非布韦）用于基因型3慢性丙型肝炎（GT-3 HCV）成人患者的治疗。Daklinza是已经证明安全性和功效的治疗基因3的HCV感染，而不需要干扰素或利巴韦林共同给药的第一种药物。 Daklinza是第一个药物已显示安全性和疗效治疗基因型3 HCV感染无需共同给予干扰素[interferon]或利巴韦林[ribavirin]，FDA的药品评价和研究中心抗微生物产品室主任说：“今天的批准对有基因型3 HCV患者提供一个新选择，包括那些不能耐受利巴韦林患者。” 优先审评 DAKLINZA™(达卡他韦 daclatasvir)片，为口服使用 美国初次批准：2015 最近重大改变；说明书红色字体为修改部分 适应证和用途  2/2016 剂量和给药方法，治疗开始前测试  2/2016 剂量和给药方法，推荐剂量  2/2016 禁忌证 2/2016 警告和注意事项，伴随利巴韦林联用治疗风险  2/2016 作用机制 达卡他韦 是一种对丙型肝炎病毒直接作用抗病毒药(DAA) [见微生物学]。 适应证和用途 DAKLINZA是一种丙型肝炎病毒(HCV)NS5A抑制剂适用为与索非布韦[sofosbuvir]，有或无利巴韦林，为慢性HCV基因型1或3感染的治疗。 ⑴在基因型3在肝硬化患者接受DAKLINZA与索非布韦联用共12周持续病毒学反应(SVR12)率减低。 剂量和给药方法 ⑴开始前测试：HCV基因型1a有硬化，考虑测试病毒有NS5A耐药性-关联多态性的存在。 ⑵ 60mg 口服每天1次有或无食物与索非布韦有或无利巴韦林联用。 ⑶ 推荐治疗时间：12周。 ⑷ 剂量修饰：与强CYP3A抑制剂减低剂量至30 mg每天1次和与中度CYP3A诱导剂增加剂量至90mg每天1次。 剂型和规格 片：60mg和30mg 禁忌证 CYP3A的强诱导剂，包括苯妥英钠[phenytoin]，卡马西平[carbamazepine]，利福平[rifampin]，和圣约翰草[St. John’s wort.]。 警告和注意事项 心动过缓当与索非布韦和胺碘酮共同给药：在服用胺碘酮与索非布韦联用与另一个HCV直接作用药物患者可能发生严重症状性心动过缓，包括DAKLINZA(daclatasvir)，尤其是还接受β受体阻滞剂或那些具有潜在心脏合并症和/或晚期肝病患者。建议胺碘酮与DAKLINZA与索非布韦联用不要共同给药。建议在无另外治疗选择患者中监视心脏。 不良反应 DAKLINZA与索非布韦联用观察到最常见不良反应(≥10%)是头痛和疲乏。 用DAKLINZA与索非布韦和利巴韦林联用观察到最常见不良反应(≥10%)是头痛，贫血，疲乏，和恶心。 药物相互作用 药物相互作用：DAKLINZA的共同给药可能改变其他药物的浓度和其他药物可能改变达卡他韦的浓度。对禁忌药物和其他潜在药物-药物相互作用使用前咨询完整处方资料。 包装规格 DAKLINZA 60MG TAB 28  DACLATASVIR DIHYDROCHLORIDE     00003-0215-01      DAKLINZA 30MG TAB 28 =  DACLATASVIR DIHYDROCHLORIDE     00003-0213-01     DAKLINZA TAB 90MG 28  DACLATASVIR DIHYDROCHLORIDE     00003-0011-01 完整资料附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9803a6ff-8a3e-4c64-b3d0-7825c7123bf2 FDA Approves Daklinza (daclatasvir) for the Treatment of Patients with Chronic Hepatitis C Genotype 3 Daklinza in combination with sofosbuvir is the first 12-week, all-oral therapy that offers SVR12 for the vast majority of genotype 3 patients Hepatitis C genotype 3 is one of the most difficult-to-treat genotypes Announcement marks the first approval of Daklinza in the United States U.S. Food and Drug Administration (FDA). This approval marks the first time patients with chronic hepatitis C virus (HCV) genotype 3 have a 12-week, once-daily, all-oral treatment option. Daklinza is indicated for use with sofosbuvir for the treatment of patients with chronic HCV genotype 3 infection. Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving this regimen. The recommended dosage of Daklinza is 60 mg in combination with sofosbuvir for 12 weeks. “The U.S. approval of Daklinza means that chronic HCV genotype 3 patients may now complete treatment in just 12 weeks with an all-oral, once-daily regimen,” said Chris Boerner, Head of U.S. Commercial, Bristol-Myers Squibb. “We believe this Daklinza-based regimen may be a solution to improving the standard of care for these patients. This approval is the result of many years of partnership with the HCV community to address the complexities of genotype 3, and an important achievement in our ongoing Daklinza development program, which focuses on patients that are most challenging to treat.” The pivotal Phase III open-label ALLY-3 clinical trial enrolled 152 patients with chronic HCV genotype 3 infection and compensated liver disease (101 treatment-naïve patients and 51 treatment-experienced patients). The co-primary endpoints were sustained virologic response rates 12 weeks after completing therapy (SVR12) in each treatment group. The full study design is outlined below. In the trial the Daklinza plus sofosbuvir regimen demonstrated SVR12 in 90% of treatment-naïve and 86% of treatment-experienced chronic HCV genotype 3 patients. SVR12 rates were higher (96%) in genotype 3 patients without cirrhosis, regardless of treatment history. In the more difficult-to-treat patients with cirrhosis, SVR12 rates were reduced (63%). These SVR12 rates were achieved with 12 weeks of therapy without the use of ribavirin. Daklinza is contraindicated in combination with drugs that strongly induce CYP3A and, thus, may lead to lower exposure and loss of efficacy of Daklinza. Daklinza also may be associated with the risk of adverse reactions or loss of virologic response due to drug interactions. In addition, there is a risk of serious symptomatic bradycardia when coadministered with sofosbuvir and amiodarone. Please see full Important Safety Information below for more details. In the pivotal Phase III trial, there were no treatment-related serious adverse events (SAEs) and no discontinuations due to adverse events (AEs). The most common treatment-related AEs at a frequency of ≥5% were headache (14%), fatigue (14%), nausea (8%) and diarrhea (5%). “The treatment landscape for HCV has radically evolved in recent years, and while we have achieved impressive SVR12 rates in genotype 1, genotype 3 still represents a clinical challenge,” said David R. Nelson, M.D., Professor of Medicine, Molecular Genetics and Microbiology Director, UF Clinical and Translational Science Institute, and Assistant Vice President of Research for the University of Florida. “Not only are genotype 3 patients more complicated to manage, but the aggressive nature of their disease means there is a greater urgency to treat them. Daklinza in combination with sofosbuvir gives healthcare providers a new option to achieve a high overall SVR12 rate in this difficult-to-treat patient population.” Daklinza is an inhibitor of NS5A with dual modes of anti-viral activity that inhibits both RNA replication and virion assembly. In in vitro studies, Daklinza has shown anti-viral activity across genotypes 1-6, with EC50 values from picomolar (pM) to low nanomolar (nM) against wild type replicons. About the ALLY-3 Clinical Trial The efficacy and safety of Daklinza in combination with sofosbuvir were evaluated in the Phase III ALLY-3 clinical trial. ALLY-3 was an open-label trial that included 152 patients with chronic HCV genotype 3 infection and compensated liver disease who were treatment-naïve (n=101) or treatment-experienced (n=51). Patients received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The co-primary endpoints were defined as HCV RNA below the lower limit of quantification (LLOQ) at post-treatment week 12 (SVR12) in each treatment group. Most treatment-experienced patients had failed prior treatment with peginterferon/ribavirin, but seven patients had been treated previously with a sofosbuvir regimen and two patients with a regimen containing an investigational cyclophilin inhibitor. Previous exposure to NS5A inhibitors was prohibited. The 152 treated patients in ALLY-3 had a median age of 55 years (range, 24-73); 59% of the patients were male; 90% were white, 5% were Asian, and 4% were black. Most patients (76%) had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; 21% of the patients had compensated cirrhosis, and 40% had the IL28B rs12979860 CC genotype. About Hepatitis C Genotype 3 Genotype 3 is estimated to affect 12 percent of chronic HCV patients in the U.S. and is the second most common hepatitis C genotype globally after genotype 1. Hepatitis C genotype 3 is considered one of the most difficult-to-treat genotypes. DAKLINZA Rx Pharmacological Class: HCV NS5A inhibitor. Active Ingredient(s): Daclatasvir 30mg, 60mg; tablets. Company Bristol-Myers Squibb Indication(s): In combination with sofosbuvir, for the treatment of chronic hepatitis C virus (HCV) genotype 3 infection. Limitations of use: sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving daclatasvir with sofosbuvir for 12 weeks. Pharmacology: Daclatasvir inhibits NS5A, a nonstructural protein encoded by HCV, by binding to the N-terminus within Domain 1 and thereby inhibiting both viral RNA replication and virion assembly. Clinical Trials: The safety and efficacy of Daklinza in combination with sofosbuvir were supported by data from ALLY-3, a Phase 3, open-label trial that included 152 treatment-naive (n =101) or treatment-experienced (n = 51) subjects with chronic HCV genotype 3 infection and compensated liver disease. Most treatment-experienced subjects had failed prior treatment with peginterferon/ribavirin, but 7 subjects had been treated previously with a sofosbuvir regimen and 2 subjects with a regimen containing an investigational cyclophilin inhibitor. Previous exposure to NS5A inhibitors was prohibited. Subjects received Daklinza 60mg plus sofosbuvir 400mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The primary endpoint was sustained virologic response (SVR), defined as HCV RNA <25 IU/mL at post-treatment week 12. Overall, post-treatment results demonstrated that the majority of the subjects, 89%, achieved SVR (90% in treatment-naive group vs. 86% in treatment-experienced group). In 120 subjects without cirrhosis, 96% achieved SVR (98% in treatment-naive group vs. 92% in treatment-experienced group). The presence of cirrhosis reduced SVR rates in both treatment-naive and treatment-experienced groups, 58% and 69%, respectively. For subjects not achieving SVR, 0.7% had on-treatment virologic failure and 11% relapsed. For more clinical trial data, see full labeling. Legal Classification: Rx Adults: ≥18 years: 60mg once daily for 12 weeks (with sofosbuvir). Concomitant strong CYP3A inhibitors (eg, clarithromycin, itraconazole, ketoconazole, ritonavir): reduce to 30mg once daily. Concomitant moderate CYP3A inducers (eg, bosentan, dexamethasone, efavirenz, etravirine, modafinil, nafcillin, rifapentine): increase to 90mg once daily. If sofosbuvir is permanently discontinued, daclatasvir should also be discontinued. Children: <18 years: not established. Contraindication(s): Concomitant strong CYP3A inducers (eg, phenytoin, carbamazepine, rifampin, St. John’s wort). Warnings/Precautions: Increased risk of symptomatic bradycardia when concomitant amiodarone and with sofosbuvir, esp. in patients taking beta-blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Decompensated cirrhosis. Liver transplant patients. Pregnancy. Nursing mothers. Interaction(s) See Adults & Contraindications. Concomitant amiodarone with daclatasvir in combination with sofosbuvir: not recommended; if no alternatives, monitor cardiac function. May potentiate P-gp, OATP 1B1, OATP 1B3, or BCRP substrates, statins (monitor). May be potentiated by strong CYP3A inhibitors. Concomitant moderate CYP3A inhibitors (eg, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil); monitor. Potentiates dabigatran etexilate mesylate: not recommended in specific renal impairment groups (see full labeling). Concomitant digoxin: if already on daclatasvir, initiate digoxin at lowest appropriate dose and monitor; if already receiving digoxin prior to daclatasvir initiation, reduce digoxin dose by 30–50% or modify dosing frequency and monitor. Adverse Reaction(s) Headache, fatigue, nausea, diarrhea; symptomatic bradycardia. How Supplied: Tabs—28 LAST UPDATED: 8/21/2015