英文药名: Incivek(telaprevir,Tadlets) 中文药名: 替拉瑞韦片 生产厂家: Not available 药品介绍 **慢性丙型肝炎治疗新药FDAIncivek(telaprevir)片获美国食品与药物管理局（FDA）批准上市** 批准日期：2011年5月23日：公司：Vertex Pharmaceuticals Incorporated 美国食品与药物管理局（FDA）发布公告，批准Incivek（活性成分：telaprevir）与聚乙二醇干扰素α和利巴韦林联合使用，用于治疗未经干扰素为基础的抗感染药物治疗的患者、或对此类治疗反应不佳的患者。 此前，FDA已批准了另一个治疗慢性丙型肝炎的新药Victrelis（活性成分：boceprevir）。目前对慢性丙型肝炎病毒感染患者的标准治疗是使用48周的聚乙二醇干扰素α和利巴韦林。不到50%的患者对这种疗法产生应答。3项3期临床试验评估了Incivek的安全性和有效性。有大约2250例成人患者被纳入研究，他们之前有的未经治疗，有的接受过治疗。所有研究中，患者同时接受了标准治疗药物。在以前未经治疗的患者中，与单独的标准治疗相比，接受Incivek治疗的患者中有79%呈现持续性病毒学应答（即停止治疗后24周，血液中不再检出病毒感染）。所有研究、所有患者分组中，Incivek治疗组产生持续性病毒学应答的患者比标准治疗组高出20%—45%。 研究表明，对于大多数患者，Incivek的治疗时间可从48周缩短至24周。60%以前未经治疗的患者取得了早期应答，并接受了仅24周的治疗（相比于标准治疗的48周）。这些患者有90%达到了持续性病毒学应答。当患者结束治疗后达到持续性病毒学应答，则表明丙型肝炎病毒感染已被治愈。持续性病毒学应答可减少肝硬化和肝病并发症、降低肝癌（肝细胞癌）率、降低死亡率。 Incivek每日服用3次，于进餐时服用。前12周，Incivek应与聚乙二醇干扰素α和利巴韦林联合应用。大部分对Incivek联合方案有良好早期应答的患者可采用24周疗程，而不是采用标准治疗时建议的48周。 接受Incivek联合聚乙二醇干扰素α和利巴韦林治疗的患者最常见的副作用包括皮疹、红细胞计数降低（贫血）、恶心、疲劳、头痛、腹泻、瘙痒以及肛门或直肠刺激和疼痛。皮疹可能很严重，可能需要停用Incivek或所有治疗方案中的3种药物。 适应症: INCIVEK是一种丙型肝炎病毒(HCV)NS3/4A蛋白酶抑制剂适用于，与聚乙二醇干扰素α和利巴韦林联用，对有代偿肝病成年患者中基因型1慢性丙型肝炎(CHC)的治疗，包括肝硬变，未治疗过患者或既往曾被基于干扰素治疗治疗过患者，包括既往零反应者(注：治疗期间丙型肝炎病毒负荷达到很小或无减低)，部分反应者，和复发者。 （1）INCIVEK必须不用作单药治疗和必须只与聚乙二醇干扰素α和利巴韦林联用。 （2）既往零反应者的高比例(尤其是有肝硬变患者)未达到持续病毒学反应(SVR)和有telaprevir出现对用INCIVEK治疗伴耐药取代。 （3）对既往用包括INCIVEK或其它HCV NS3/4A蛋白酶抑制剂治疗方案已治疗失败患者，INCIVEK疗效尚未确定。 用法用量: （1）750 mg一天服用3次(间隔7-9小时)与食物(非低脂肪)。 （2）对所有患者INCIVEK必须与聚乙二醇干扰素α和利巴韦林二者给予共12周，接着反应-指导方案或12或36另外周的聚乙二醇干扰素α和利巴韦林依赖于病毒反应和既往反应状态。 （3）对聚乙二醇干扰素α和利巴韦林专门剂量说明，参阅其相应处方资料。 禁忌症: （1）因为INCIVEK必须与聚乙二醇干扰素α和利巴韦林给药，对聚乙二醇干扰素α和利巴韦林所有禁忌证也应用。 （2）妊娠妇女和男性其女性伴侣妊娠：因为利巴韦林可能引起出生缺陷和胎儿死亡，在妊娠妇女和在男性其女性伴侣妊娠禁忌用telaprevir与聚乙二醇干扰素α和利巴韦林联用。 （3）与以下药物共同给药： 1）对清除高度依赖于CYP3A和升高血浆浓度是伴随严重和/或危及生命事件。 2）强烈诱导CYP3A 可能导致脚底保留和丧失INCIVEK疗效。 警告和注意事项: （1）妊娠：使用利巴韦林和Peg干扰素α：利巴韦林可能引起出生缺陷和胎儿死亡；在女性患者和男性患者的女性伴侣中避免妊娠。初始治疗前患者必须有阴性妊娠检验，采用至少2种有效避孕方法，和每月进行妊娠检验。 （2）严重皮肤反应：严重皮肤反应包括药物皮疹有嗜酸粒细胞增多和全身症状和曾报道Stevens-Johnson综合征。对严重皮肤反应，应立即终止INCIVEK联合治疗的所有化合物。 （3）皮疹：有轻至中度皮疹患者应监视进展。如皮疹进展和成为严重，应终止INCIVEK。 （4）贫血：INCIVEK联合治疗前和期间定期监视血红蛋白。调整利巴韦林剂量；如需要终止INCIVEK。 不良反应: 最常见对INCIVEK不良药物反应 (发生率用NCIVEK比对照至少较高5%)是皮疹，瘙痒，贫血，恶心，痔疮，腹泻，肛门直肠不适，味觉障碍，疲乏，呕吐，和肛门瘙痒。 药物相互作用: INCIVEK治疗与其它药物联用共同给药可能改变其它药物的浓度和可能改变telaprevir浓度的其它药物。对药物-药物相互作用潜能治疗期间和前咨询完整处方资料。 特殊人群中使用: （1）肝受损：尚未确定在有Child-Pugh评分大于或等于7(类型B和C)患者中安全性和疗效。 （2）共感染：尚未确定在HCV/HIV和HCV/HBV共感染患者中安全性和疗效。 （3）儿童：尚未确定在儿童患者中安全性和疗效。 （4）实体器官移植：尚未确定在进行实体器官移植患者中安全性和疗效。 Manufacturer: Vertex Pharmaceuticals Pharmacological Class: Hepatitis C virus NS3/4A protease inhibitor. Active Ingredient(s): Telaprevir 375mg; tablets. Indication(s): Chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin in patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have previously been treated with interferon-based therapy, including prior null responders, and relapsers. Not for use as monotherapy. Pharmacology: Telaprevir works by inhibiting the HCV NS3/4A serine protease enzyme. Clinical Trials: A study was conducted in treatment-naïve patients to evaluate the safety and efficacy of telaprevir. Sustained virologic response (SVR) was defined as HCV-RNA <25 IU/mL at 24 weeks after the planned end of treatment. Telaprevir was given for the first 8 weeks (T8/PR) or the first 12 weeks of treatment (T12/PR) in combination with peginterferon alfa and ribavirin (peg-IFN-alfa-2a/RBV) for either 24 or 48 weeks. Subjects who had undetectable HCV-RNA at Weeks 4 and 12 received 24 weeks of peg-IFN-alfa-2a/RBV; those who did not have undetectable levels received 48 weeks of peg-IFN-alfa-2a/RBV. The control group received placebo for the first 12 weeks and peg-IFN-alfa-2a/RBV for 48 weeks. The overall SVR for the T12/PR group was 79% vs. 46% for placebo. In the T8/PR group, overall SVR was 72%. In another study, prior relapsers and nonresponders were randomized to either of two telap­revir groups (with/without peg-IFN-alfa-2a/RBV lead-in) or control group. The SVRs for each of the study drug groups were significantly higher than the control groups (86% vs. 22%) for prior relapsers, 59% vs. 15% for prior partial responders, and 32% vs. 5% for prior null responders. Legal Classification: Rx Adults: Take with food (not low fat). 750mg three times daily. Treat for 12 weeks (with peginterferon + ribavirin), then continue peginterferon + ribavirin according to HCV-RNA response at Weeks 4 and 12. Do not reduce dose or interrupt therapy. Discontinue if futile (see literature). Children: ≤18 years: not recommended. Contraindication(s): Concomitant strong CYP3A inducers (eg, rifampin, St. John’s wort), or narrow therapeutic index CYP3A substrates (eg, alfuzosin, ergots, atorvastatin, lovastatin, simvastatin, sildenafil/tadalafil for PAH, triazolam, oral midazolam). Pregnant women, or partners. Review peginterferon and ribavirin contraindications. Warnings/Precautions: Must have (–) pregnancy test before therapy, use effective contraception, and undergo monthly pregnancy test. Monitor for serious skin reactions (eg, DRESS, Stevens-Johnson syndrome). Moderate/severe hepatic impairment, decompensated liver disease: not recommended. Coinfection with HBV or HIV. Organ transplant recipients. Monitor hemoglobin, CBC with differential, HCV-RNA, and clinical chemistry. Pregnancy (Cat. B). Nursing mothers: not recommended. Interaction(s): Concomitant colchicine w/renal or hepatic impairment, voriconazole; lopinavir, fosamprenavir, darunavir (all w/ritonavir): not recommended. May be potentiated by macro­lides, azole antifungals. May be antagonized by anticonvulsants, rifabutin, dexamethasone, HIV pro­tease inhibitors, efavirenz. May potentiate anti­arrhythmics, digoxin, macrolides, carbamaz­e­pine, desipramine, trazodone, azole antifungals, colchicine, rifabutin, alprazolam, midazolam, calcium channel blockers, cortico­steroids, bosentan, atazanavir, tenofovir, immunosuppressants, salmet­erol, PDE5 inhibitors for ED (reduce dose). May antagonize escitalopram, zolpidem, efavirenz, ethinyl estradiol, methadone. Monitor warfarin. Adverse Reaction(s): Rash (if serious; discontinue therapy and treat, do not restart), pruritus, anemia, GI upset, anorectal effects, dysgeusia, fatigue, hyperbilirubinemia, hyperuricemia. How Supplied: Tabs (blister pack or bottle)—168 Last Updated: 7/14/2011 INCIVEK(telaprevir)是一种HCV NS3/4A蛋白酶的抑制剂 Telaprevir药物质是一种白至淡白色粉有水中溶解度0.0047 mg/mL。Telaprevir相互转换为一种R-非对映体, VRT-127394，是血浆中主要代谢物和效力比telaprevir较弱接近30-倍。可得到为口服给药INCIVEK紫色，胶囊、膜衣片含375mg telaprevir。每片含无活性成分胶体二氧化硅，交联羧甲基纤维素钠，D&C红No. 40，磷酸氢钙(无水)，FD&C蓝No. 2，醋酸琥珀羟丙甲纤维素，微晶纤维素，聚乙二醇, 聚乙烯醇, 十二烷基硫酸钠，硬脂富马酸钠，滑石粉，和二氧化钛。 INCIVEKTM (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age. IMPORTANT SAFETY INFORMATION Who should not take INCIVEK? Do not take INCIVEK if you are pregnant or may become pregnant, or if you are a man with a sexual partner who is pregnant. Do not take INCIVEK if you are taking certain medicines as there could be serious side effects. If these drugs are taken together, this can cause you to have too much or not enough INCIVEK or your other medicines in your body. It can also cause side effects that can be serious or life-threatening. These medicines include: alfuzosin hydrochloride (Uroxatral®), atorvastatin (Lipitor®, Caduet®), ergot containing medicines such as methylergonovine (Methergine®), lovastatin (Advicor®, Altoprev®, Mevacor®), pimozide (Orap®), rifampin (Rifadin®, Rifamate®, Rifater®), sildenafil citrate (Revatio®) or tadalafil (Adcirca®) for the lung problem pulmonary artery hypertension (PAH), simvastatin (Zocor®, Vytorin®, Simcor®), St. John’s wort (Hypericum perforatum), or triazolam (Halcion®). Talk to your healthcare provider before taking INCIVEK if any of the above applies to you. Your healthcare provider may need to change the amount of medicines you take. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. INCIVEK and other medicines can affect each other. Serious Side Effects INCIVEK can cause serious side effects, including: Birth defects or death of an unborn baby INCIVEK combined with peginterferon alfa and ribavirin may cause birth defects or death of your unborn baby. If you or your sexual partner is pregnant or plan to become pregnant, do not take these medicines. You or your partner should not become pregnant while taking INCIVEK with peginterferon alfa and ribavirin and for 6 months after treatment is over. You must have a negative pregnancy test before starting treatment, every month during treatment, and for 6 months after your treatment ends. You must use 2 effective methods of birth control during treatment and for 6 months after all treatment has ended. These 2 forms of birth control should not contain hormones, as these may not work as well during treatment with INCIVEK. Talk to your healthcare provider about the forms of birth control you should use during this time. Two weeks after stopping INCIVEK, you can use a hormonal form of birth control as one of your two forms of birth control. If you or your partner becomes pregnant during treatment or within 6 months after stopping these medicines, tell your healthcare provider right away. Contact the Ribavirin Pregnancy Registry right away by calling 1-800-593-2214. The Registry collects information about what happens to mothers and their babies if the mother takes ribavirin while pregnant. Skin reactions: Mild skin rashes are common with INCIVEK combination treatment. Sometimes these skin rashes and other skin reactions can become severe and require treatment in a hospital. Call your healthcare provider right away if you develop any skin changes with these symptoms: rash with or without itching, blisters or skin lesions, mouth sores or ulcers, red or inflamed eyes like “pink eye” (conjunctivitis), swelling of your face, or fever. Your healthcare provider will decide if these changes may be a sign of a serious skin reaction. Your healthcare provider will also decide if you need treatment for your rash or to stop INCIVEK or your other medicines. Never stop taking INCIVEK combination treatment without talking to your healthcare provider first. Do not take INCIVEK alone to treat chronic hepatitis C infection. It must be used with peginterferon alfa and ribavirin to treat chronic hepatitis C infection. Low red blood cell count (anemia) that can be severe. Tell your healthcare provider if you have any of these symptoms of anemia: dizziness, shortness of breath, tiredness, or weakness. Your healthcare provider will do blood tests regularly to check your red blood cell count during treatment. If your anemia is severe your healthcare provider may tell you to stop taking INCIVEK. If this happens, do not start taking it again. What should I tell my healthcare provider before taking INCIVEK? Tell your healthcare provider if you: • have certain blood problems such as anemia • have liver problems other than hepatitis C infection • have hepatitis B, HIV infection, or any problems with your immune system • have a history of gout or high uric acid levels in your blood • have had an organ transplant • plan to have surgery • have any other medical condition • are breastfeeding How should I take INCIVEK? Take INCIVEK exactly as your healthcare provider tells you. Take two INCIVEK pills 3 times a day, 7 to 9 hours apart, with food. Eat a meal or snack containing about 20 grams of fat within 30 minutes before you take each dose. Talk to your healthcare provider about examples of food you can eat. If you miss a dose within 4 hours of when you usually take it, take your dose with food as soon as possible. If you miss a dose and it is more than 4 hours after the time you usually take it, skip that dose only and take the next dose at your normal time. Do not stop taking INCIVEK unless your healthcare provider tells you to. If your healthcare provider tells you to stop, you should not start taking it again, even if the reason for stopping goes away. If you take too much INCIVEK, call your healthcare provider or local Poison Control Center, or go to the nearest emergency room right away. Common Side Effects of INCIVEK Combination Treatment The most common side effects include itching, nausea, diarrhea, vomiting, anal or rectal problems (including hemorrhoids, discomfort or burning around or near the anus, itching around or near the anus), taste changes, and tiredness. Tell your healthcare provider about any side effect that bothers you or doesn’t go away. These are not all the possible side effects of INCIVEK. For more information, ask your healthcare provider or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/Safety/MedWatch, or call 1-800-332-1088.