800 mg 每天口服三次给药(每7-9小时)与食物(一餐或小吃).
为报告怀疑不良反应，联系Schering Corporation，Merck & Co., Inc.的子公司电话1-877-888-4231或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.
Victrelis (boceprevir) is indicated for use in combination with peginterferon alfa and ribavirin to treat chronic hepatitis C (HCV) genotype 1 infection in patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Boceprevir is the first agent to directly target the hepatitis C virus
Boceprevir directly inhibits the HCV NS3 protease, which is essential for viral replication.1
Two randomised, placebo-controlled double-blind phase 3 studies evaluated the efficacy of boceprevir in the treatment of chronic HCV genotype 1 infection, the most common form of the disease. Added to the current standard of care (pegylated interferon plus ribavirin), boceprevir 800mg 3 times daily significantly increased sustained virologic response rates (defined as an undetectable HCV RNA level after 24 weeks of follow-up) in both studies.
SPRINT-2 enrolled 1097 previously untreated patients, who were randomised to 1 of 3 treatment arms.2 Patients in all 3 arms underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin alone. The control group then received add-on placebo for 44 weeks, while the other 2 groups were assigned to add-on boceprevir for either 44 or 24 weeks. Treatment in the 24-week group was guided by response, with patients who had a detectable HCV RNA level between weeks 8 and 24 switching to placebo plus peginterferon alfa-2b and ribavirin for another 20 weeks.
Among non-black patients (n=938), sustained virologic response rates for boceprevir plus peginterferon and ribavirin were significantly greater than for placebo plus peginterferon and ribavirin: 68% (44 weeks’ treatment) and 67% (24 weeks’ treatment) versus 40% (p<0.001 for both). Black patients (n=159), who typically show a poorer response to HCV treatment, exhibited corresponding response rates of 53% (p=0.004), 42% (p=0.04) and 23%, respectively. Overall, treatment with boceprevir increased the likelihood of a sustained virologic response more than three-fold (p<0.001).2
RESPOND-2 enrolled 403 patients who had previously relapsed or failed to respond to peginterferon plus ribavirin.3 As in SPRINT-2, all participants underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin. Patients then received either additional placebo for 44 weeks, or boceprevir for 44 or 32 weeks; those in the 32-week group who had a detectable HCV RNA level at week 8 (but not at week 12) received placebo plus peginterferon and ribavirin for an additional 12 weeks.
Sustained virologic response rates were similar in patients who received 44 or 32 weeks of boceprevir (66% and 59%, respectively) and significantly higher with boceprevir than placebo (21%; p<0.001 for both).3
Adverse events most commonly associated with boceprevir were fatigue, nausea, headache, anaemia and dysgeusia.1 In SPRINT-2, anaemia necessitated dose reduction in 13% of control patients and 21% of boceprevir recipients, and discontinuation in 1% and 2%, respectively.1
In a pooled analysis of the two phase 3 studies, resistance-associated HCV amino acid variants were detected in 15% of boceprevir-treated patients and in 53% of those who did not achieve a sustained virologic response.1
Merck & Co., Inc.
Pharmacological Class:HCV NS3/4A protease inhibitor
Active Ingredient(s):Boceprevir 200mg; caps.
Indication(s):Chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (PR) in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. Not for use as monotherapy.
Pharmacology:Boceprevir inhibits the hepatitis C virus (HCV) non-structural protein 3 serine protease by reversibly binding to an active site on this enzyme, thereby inhibiting viral replication in HCV-infected host cells.
Clinical Trials:In a placebo-controlled study, adding boceprevir to PR significantly increased the sustained virologic response rates compared to PR alone. In subjects with cirrhosis at baseline, the sustained virologic response was higher in those who were given boceprevir + PR for 44 weeks (after lead-in therapy with PR) compared to those given response-guided therapy based on results at treatment weeks 8 through 24.
In another study, in patients who failed previous therapy with PR, adding boceprevir to PR significantly increased the sustained virologic response rates compared to PR alone. In those with cirrhosis at baseline, sustained virologic response was higher in patients treated with boceprevir + PR for 44 weeks (after lead-in therapy with PR) compared to those who received response-guided therapy.
Adults:≥18yrs: Take with food. 800mg three times daily. Start after 4 weeks therapy with peginterferon and ribavirin. Without cirrhosis: continue treatment as indicated by HCV-RNA levels at weeks 8, 12, and 24 (see literature). With cirrhosis: continue for 44 weeks. Do not reduce dose. Discontinue if HCV-RNA levels indicate futility (see literature).
Children:<18yrs: not recommended.
Contraindication(s):Concomitant potent CYP3A4/5 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort) or narrow therapeutic index CYP3A4/5 substrates (eg, alfuzosin, cisapride, ergot derivatives, lovastatin, simvastatin, drosperinone, pimozide, sildenafil or tadalafil for PAH, triazolam, oral midazolam). Pregnant women and men whose partners are pregnant (note: ribavirin is Cat.X). Review peginterferon and ribavirin contraindications.
Warnings/Precautions:Female patients and partners must have (–) pregnancy test before therapy, use appropriate effective contraception, and undergo monthly pregnancy test. Monitor CBC w. differential, HCV-RNA. Co-infection with HBV or HIV. Decompensated cirrhosis. Organ transplant recipients. Pregnancy (Cat.B). Nursing mothers: not recommended.
Interaction(s):See literature. Concomitant rifabutin, salmeterol, efavirenz, concomitant colchicine in renal or hepatic impairment: not recommended. Potentiates CYP3A4/5 substrates (eg, amiodarone, bepridil, propafenone, quinidine, flecainide, trazodone, desipramine, azole antifungals, clarithromycin). Antagonizes ethinyl estradiol. Antagonized by potent CYP3A4/5 inhibitors. Monitor warfarin, digoxin, dihydropyridine calcium channel blockers, bosentan, protease inhibitors, immunosuppressants, opioids. Concomitant ketoconazole, itraconazole: max 200mg/day. Concomitant atorvastatin: max 20mg/day. Colchicine, PDE5 inhibitors for ED (eg, sildenafil, tadalafil, vardenafil), alprazolam, IV midazolam: reduce doses and monitor. Corticosteroids: avoid, monitor if needed.
Adverse Reaction(s):Fatigue, nausea, headache, dysgeusia, worsening anemia, neutropenia.
How Supplied:Bottles (12 caps/bottle)—28
简介： 日前，美国FDA于2011年5月批准美国默克公司的慢性丙型肝炎治疗新药波普瑞韦（Boceprevir，商品名Victrelis）上市。Victrelis是默沙东研制的用于治疗基因1型丙型肝炎的新药。临床试验数据显示，当这种药 ...