2015年1月17日，欧盟委员会批准Viekirax和Exviera，有或无利巴韦林方案上市，用于治疗基因1型和4型慢性丙型肝炎。 Viekirax（omitasvir/paritaprevir/利托那韦，AbbVie）和Exviera（dasabuvir，AbbVie）联合是一种全口服、无干扰素方案，包含固定剂量的蛋白酶抑制剂利托那韦，100mg/150mg，与25mg ombitasvir配方，每天给药一次，同时使用250mg dasabuvir有或无利巴韦林，每天两次。 除了基因1a型HCV合并肝硬化患者（应使用24周）外，其他患者应使用联合方案12周，有或无利巴韦林。对于基因4型慢性HCV患者，方案应包括viekirax，每日一次，利巴韦林，每日两次。接受阿片类药物替代治疗和肝脏移植的HIV-1合并感染患者，也可使用该方案治疗。 “随着欧盟对Viekirax+Exviera方案的批准，提供了一种可实现GT1和GT4慢性丙型肝炎患者高治愈率的治疗方案，”研究和开发执行副总裁兼AbbVie首席科学官，Michael Severino博士，在新闻稿中说。“这是我们不断将科学创新应用于有前景的医药研发而促进公众健康的重要组成部分。” 多个3期研究-SAPPHIRE-I，SAPPHIRE-II，PEARL-II，PEARL-III，PEARL-IV和TURQUOISE-II数据显示，该方案毫不逊色。超过2300例患者接受直接抗病毒治疗方案，治疗的耐受性较好。 注：以下二种产品均可提供，购买以询问为准 包装规格： VIEKIRAX® 12.5MG/75MG/50MG FILM-COATED TABLETS &EXVIERA® 250MG FILM-COATED TABLETS PRESCRIBING INFORMATION PRESENTATION: Each Viekirax film-coated tablet contains 12.5 mg of ombitasvir, 75 mg of paritaprevir and 50 mg of ritonavir. Each Exviera tablet contains 250 mg of dasabuvir. Please refer to the respective Summary of Product Characteristics’ (SmPC) before prescribing. INDICATION: For treatment of Chronic Hepatitis C (CHC) in combination with other medicinal products in adults. DOSAGE AND ADMINISTRATION: Oral. Treatment to be initiated and monitored by physician experienced in CHC management. See SmPC for full posology. Dosage: The recommended dose of Viekirax is two 12.5 mg/75 mg/ 50 mg tablets once daily with food. The recommended dose of Exviera is one 250 mg tablet twice daily (morning and evening) with food. Recommended Co-administered medicinal product(s) and Treatment Duration: Genotype 1b without cirrhosis: Viekirax+Exviera for 12 weeks. Genotype 1b with compensated cirrhosis and genotype 1a without cirrhosis: Viekirax + Exviera + ribavirin for 12 weeks. Genotype 1a with compensated cirrhosis: Viekirax + Exviera + ribavirin for 24 weeks. See SmPC for details. Genotype 4 without cirrhosis: Viekirax + ribavirin for 12 weeks. Genotype 4 with compensated cirrhosis: Viekirax+ribavirin for 24 weeks. See ribavirin SmPC for dosing instructions. Special Populations: HIV-1 Co-infection: No dose adjustment required. For dosing with HIV antiviral agents refer to SmPC for additional information. Liver Transplant recipients: Viekirax+Exviera+ribavirin for 24 weeks in liver transplant recipients with genotype 1 HCV infection. Viekirax + ribavirin in genotype 4 infected recipients. Elderly: No dose adjustment required. Renal impairment: No dose adjustment required. Hepatic impairment: No dose adjustment recommended in patients with mild hepatic impairment (Child-Pugh A). No data for patients with moderate hepatic impairment (Child-Pugh B), however, no dose adjustment expected based on pharmacokinetic studies. Viekirax is contraindicated and Exviera should not be used in patients with severe hepatic impairment (Child-Pugh C). Paediatric Population: No data available. CONTRAINDICATIONS: Hypersensitivity to any of the active substances or excipients. Ethinylestradiol-containing medicinal products such as those in most combined oral contraceptives or contraceptive vaginal rings. Viekirax is contraindicated in patients with severe hepatic impairment (Child-Pugh C). Viekirax in combination with CYP3A4 substrates: examples include; alfuzosin hydrochloride, amiodarone, astemizole, terfenadine, cisapride, colchicine in patients with renal or hepatic impairment, ergotamine, dihydroergotamine, ergonovine, methylergometrine, fusidic acid, lovastatin, simvastatin, atorvastatin, oral midazolam, triazolam, pimozide, quetiapine, quinidine, salmeterol, sildenafil (when used for the treatment of pulmonary arterial hypertension) and ticagrelor. Viekirax with or without Exviera in combination with enzyme inducers: examples include; carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, etravirine, enzalutamide, mitotane, rifampicin, St. John’s Wort (Hypericum perforatum). Viekirax with or without Exviera in combination with CYP3A4 inhibitors: examples include; cobicistat, indinavir, lopinavir/ritonavir, saquinavir, tipranavir, itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin and conivaptan. Exviera is contraindicated in combination with CYP2C8 inhibitors: example includes; gemfibrozil. SPECIAL WARNINGS AND PRECAUTIONS: Viekirax and Exviera are not recommended as monotherapies. The efficacy of Viekirax has only been established in patients with Hepatitis C Virus (HCV) genotypes 1 and 4. The efficacy of Exviera has been only been established in patients with HCV genotype 1 only. There are no data on the use of Viekirax and ribavirin in patients with genotype 4 infection with compensated cirrhosis, therefore optimal treatment duration has not been established. Co-administration of Viekirax with other antivirals other than Exviera and/or ribavirin has not been evaluated. When used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and for 6 months after the treatment as recommended in the SmPC for ribavirin. Refer to the SmPC for ribavirin for additional information. Although ALT elevations associated with Viekirax and Exviera have been asymptomatic, patients should be instructed to watch for early warning signs of liver inflammation, such as fatigue, weakness, lack of appetite, nausea and vomiting, as well as later signs such as jaundice and discoloured faeces, and to consult a doctor without delay if such symptoms occur. Use caution when administering Viekirax with fluticasone or other glucocorticoids that are metabolised by CYP3A4. Concomitant use of inhaled glucocorticoids metabolised with CYP3A can increase systemic exposures of the glucocorticoids, and cases of Cushing’s syndrome and subsequent adrenal suppression have been reported with ritonavir-containing regimens. The safety and efficacy of Viekirax and Exviera have not been established in Hepatitis C/Hepatitis B co-infection patients. INTERACTIONS: See SmPCs for full details. Viekirax in combination with Exviera: Not Recommended: darunavir in patients with extensive PI resistance, fluvastatin and pitavastatin not recommended. Use caution and dose decrease may be needed for repaglinide. Use Caution: sulfasalazine, erythromycin, trazodone (lower dose of trazodone may be considered), fexofenadine, diltiazem, verapamil, rilpivirine once daily should only be used in patients without known QT prolongation, and without other QT prolongation co-medications. Monitor Levels: digoxin, warfarin (INR), Adjust Dose: Monitoring and dose reduction recommended for valsartan. Monitoring and lower doses of imatinib recommended. Monitoring and dose adjustment may be needed for s-mephenytoin. Reduction in colchicine dose or interruption of colchicine treatment is recommended in patients with normal renal or hepatic function. Decrease amlodipine dose by 50% and monitor. Decrease nifedipine dose and monitor. Furosemide decrease of up to 50% may be required upon monitoring. 300 mg dose of atazanavir recommended to be administered at the same time as Viekirax with Exviera, 800 mg darunavir once-daily without ritonavir recommended to be administered at the same time as Viekirax with Exviera in the absence of extensive PI resistance. Do not exceed 5 mg/day rosuvastatin. Reduce pravastatin dose by 50%. When starting co-administration, give one fifth of the total daily dose of ciclosporin once daily, monitor ciclosporin levels and adjust dose and/or dosing frequency as needed. When starting co-dosing, administer 0.5 mg tacrolimus once every week, monitor and adjust dose and/or dosing frequency as needed. Use higher doses of omeprazole if clinically indicated. Higher doses of esomeprazole/lansoprazole may be needed if clinically indicated. A decrease in alprazolam dose can be considered based on clinical monitoring. Clinical monitoring and dose adjustment may be required for levothyroxine Viekirax without Exviera: As per combination with Exviera with following exceptions. Use Caution: dabigatran etexilate Not Recommended: Atazanavir and darunavir are not recommended with Viekirax without Exviera. Adjust Dose: Decrease digoxin dose by 30–50% and monitor. Do not exceed 10 mg/day rosuvastatin. PREGNANCY AND LACTATION: When Viekirax and Exviera are taken in combination with ribavirin, the contraindications regarding the use of ribavirin in pregnancy apply. See the ribavirin SmPC for information. Extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients when co-administered with ribavirin. There is only limited data on the use of Viekirax and Exviera in pregnant women. The potential risk to humans is unknown. Viekirax and Exviera should not be used in pregnancy. It is not known whether Viekirax, Exviera and their metabolites are excreted in human breast milk. SIDE EFFECTS: See SmPC for full details on side effects. Side-effects identified with Viekirax in combination with Exviera Common side effects (≥1/100 to <1/10): pruritus Side-effects identified with Viekirax in combination with Exviera and ribavirin Very common side effects (≥1/10):insomnia, nausea, pruritus, asthenia and fatigue. Common side effects (≥1/100 to <1/10):anaemia. LEGAL CATEGORY: POM MARKETING AUTHORISATION NUMBERS/PRESENTATIONS/BASIC NHS COST: Viekirax 12.5mg/75 mg/50 mg film-coated tablets; daily blister packs containing 2 film-coated tablets, inner cartons containing 14 film-coated tablets in multipack presentation containing 56 (4 packs of 14) film-coated tablets. EU/1/14/982/001 £10,733.33 Exviera 250 mg film-coated tablets; daily blister packs containing 2 film-coated tablets, inner cartons containing 14 film-coated tablets in multipack presentation containing 56 (4 packs of 14) film-coated tablets. EU/1/14/983/001 MARKETING AUTHORISATION HOLDER: AbbVie Ltd, Maidenhead, SL6 4XE DATE OF REVISION: January 2015