2011年5月23日，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，在5月13日，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药丸每日服用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。
INCIVEK® (telaprevir) Tablets
October 28, 2013
Subject:
DOSAGE AND ADMINISTRATION for INCIVEK (telaprevir) changed to twice-daily; new packaging changeover timeline; and addition of anticonvulsants to CONTRAINDICATIONS
Dear Healthcare Professional:
Vertex Pharmaceuticals Incorporated would like to inform you of changes to the Dosage and Administration of INCIVEK (telaprevir), provide updates on the new packaging changeover timeline and important safety information. INCIVEK is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated, in combination with peginterferon alfa and ribavirin, for the treatment of genotype 1 chronic HCV in adult patients with compensated liver disease. The complete indication for INCIVEK is located at the end of this letter.
Changes to the Dosage and Administration of INCIVEK
The Dosage and Administration for INCIVEK has changed:
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The new recommended dose of INCIVEK tablets is 1,125 mg (three 375-mg tablets) taken orally 2 times a day (10-14 hours apart) with food (not low fat).
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The recommended duration of treatment with INCIVEK is 12 weeks in combination with peginterferon alfa and ribavirin. An additional 12 or 36 weeks of peginterferon alfa and ribavirin is required (see INCIVEK prescribing information).
This change in dosing frequency was based on data from a clinical trial demonstrating similar sustained virologic response and safety profile between the twice-daily dosing and the every-8-hour dosing.
New Packaging Changeover Timeline
INCIVEK is currently available only as a 28-day pack containing 4 weekly cartons of 7 blister strips to support dosing every 8 hours (6 tablets per blister).
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New packaging with blister strips to support twice-daily dosing will be available for dispensing by the end of January 2014.
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There may be a brief period of time when both packages will be on the market.
INCIVEK twice-daily dosing has the same total daily dose (2,250 mg) and same total tablet count (6) as every 8 hour dosing. In the interim, twice-daily dosing can be achieved with the current packaging [6 tablets per blister strip with 3 blister sections containing 2 tablets each (see image below)]. For example, each dose of three tablets (1,125 mg) can be achieved by taking two tablets from one blister section and one tablet from another blister section.
INCIVEK
(telaprevir) |
Three-times-a-day dosing package
(Currently available) |
Twice-daily dosing package
(Available end of January 2014) |
|
Package |
 |
 |
Blister
Appearance
(front) |
 |
 |
|
NDC |
51167-100-01 |
51167-100-03 |
Additional Contraindicated Drugs
The anticonvulsant medications carbamazepine, phenobarbital and phenytoin have been added to the list of CONTRAINDICATIONS. This change was based on a pharmacokinetic study demonstrating that co-administration of these drugs with INCIVEK has the potential to lower exposure and, thus, may result in a loss of efficacy of INCIVEK.
Please read the enclosed US Prescribing Information and Medication Guide for complete information on the dosage and administration of INCIVEK and important safety information including the list of contraindicated medications.
Should you have any questions, require further information, or wish to report adverse patient experiences associated with the use of INCIVEK, please call:
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Vertex Medical Information at 1-877-824-4281.
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Alternatively, report this information to FDA’s MedWatch reporting system by phone (1-800-FDA-1088), by facsimile (1-800-FDA-0178), online (www.accessdata.fda.gov/scripts/medwatch) or by mail via the MedWatch Form FDA 3500, to the FDA Medical Products Reporting Program, 5600 Fishers Lane, Rockville, MD 20852-9787.
The complete indication for INCIVEK is as follows:
INCIVEK (telaprevir), in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have previously been treated with interferon-based treatment, including prior null responders, partial responders, and relapsers.
The following points should be considered when initiating treatment with INCIVEK:
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INCIVEK must not be administered as monotherapy and must only be prescribed with both peginterferon alfa and ribavirin.
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A high proportion of previous null responders (particularly those with cirrhosis) did not achieve a Sustained Virologic Response (SVR) and had telaprevir resistance-associated substitutions emerge on treatment with INCIVEK combination treatment.
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INCIVEK efficacy has not been established for patients who have previously failed therapy with a treatment regimen that includes INCIVEK or other HCV NS3/4A protease inhibitors.
