Sofosbuvir and Daclatasvir

Sofosbuvir and Daclatasvir

ブランド: Natco Pharma, India
品番: 201404072772
在庫: 在庫あり
460円
-+
2 点以上ご注文の場合 440円 3 点以上ご注文の場合 420円 5 点以上ご注文の場合 399円

Sofosbuvir & Daclatasvir

Daclatasvir–sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life

Abstract

The treatment of hepatitis C virus has changed dramatically with the rapid advent of numerous new antiviral agents, including direct-acting antivirals and agents with non-viral targets (cyclophilin inhibitors, interferon-lambda, vaccine therapy). Given the better safety profile and high antiviral potency of direct-acting antivirals, their combination in interferon-free oral regimens is becoming the standard of care for hepatitis C virus infection, tailored to individual patients according to the degree of disease progression (fibrosis), hepatitis C virus genotype and subtype, resistance profile, and prior therapeutic history. Results from clinical studies as well as preliminary real-life data regarding the combination of sofosbuvir (a nucleotide polymerase inhibitor) and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug–drug interactions, in addition to high antiviral potency, with >90% sustained virologic response rates. This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of sofosbuvir and an NS5A inhibitor with ribavirin for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis.

Introduction

Direct-acting antiviral agents (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection over the last 5 years. As a result of our better understanding of the HCV life cycle, specific DAAs have been developed for HCV that are able to target the viral proteins implicated in replication of the virus, ie, the NS3/4A protease, NS5B polymerase, and multifunctional NS5A replication complex. The first-generation protease inhibitors significantly improved the sustained virologic response (SVR) in genotype 1-infected patients, but at the cost of increased side effects, a complex pattern of drug–drug interactions, and viral resistance. In addition, the first-generation drugs still required the use of PEGylated interferon (PEG-IFN) for 24–48 weeks. Oral IFN-free combinations containing at least two DAAs enabled less complex dosing, tolerable side effects, and fewer drug–drug interactions. This review summarizes the key safety and efficacy data from clinical studies concerning the combination of sofosbuvir, daclatasvir, with or without ribavirin in the treatment of HCV.

Summary of pharmacology and pharmacokinetics

Daclatasvir

Daclatasvir is a first-in-class HCV NS5A replication complex inhibitor with pangenotypic activity and a pharmacokinetic profile allowing once-daily dosing. Reaching in vitro 50% effective concentrations (EC50) in the picomolar range against HCV replicons representing six major HCV genotypes (1a, 1b, 2a, 3a, 4a, 5a), daclatasvir is one of the most potent HCV replication inhibitors reported to date. Moreover, daclatasvir was generally well tolerated, with headache being the most frequently reported adverse event.

In vitro resistance selection studies (with genotype 1a and 1b replicons) have identified daclatasvir resistance-associated mutations that map to the N-terminal region of NS5A and reduced susceptibility to daclatasvir which appear to have a low to medium barrier to resistance. However, treatment with an appropriate dose of daclatasvir in combination with other agents is sufficiently potent to prevent emergence of resistance in most patients. In IFN-including and IFN-free regimens, daclatasvir has demonstrated a high level of antiviral efficacy and generally tolerable safety profile in treatment-naïve patients and in patients who have not previously responded to PEG-interferon/ribavirin.

While daclatasvir is a substrate and inhibitor of P-glycoprotein and a substrate of cytochrome P450 3A4, it is not a strong inhibitor or strong inducer of cytochrome P450 3A4 isozymes, suggesting it may have a low potential for drug–drug interactions. For example, no adjustment is needed when coadministered with tenofovir, and at 90 mg once daily with efavirenz and 30 mg once daily with atazanavir/ritonavir (300/100 mg), the exposure to daclatasvir is expected to be similar to that of daclatasvir 60 mg administered alone. No clinically significant pharmacokinetic drug interactions were observed for ethinyl estradiol, norelgestromin, and norgestrel exposures. In addition, as for most protease inhibitors, the metabolism of NS5A inhibitors is mainly hepatic, which allows their use without any dose adjustment in patients with chronic kidney disease.

Sofosbuvir

Sofosbuvir is an orally administered HCV nucleotide polymerase NS5B inhibitor. It is given once daily, and has a good safety profile. It has a high barrier to resistance, a pangenotypic antiviral effect, and few drug–drug interactions (although there is a recent US Food and Drug Administration warning concerning comedication with amiodarone or spironolactone). Combination of sofosbuvir and daclatasvir with or without ribavirin has been well tolerated in previously treated or untreated HCV patients.

Daclatasvir plus sofosbuvir works well for people with genotype 3 hepatitis C and advanced liver disease in real-world clinical practice.

buygenericmedicinewithbitcoin, BuySofosbuvirandDaclatasvir, BuySofosbuvirandDaclatasvirOnline, SofosbuvirandDaclatasvirpriceinusa, SofosbuvirandDaclatasvirpriceinIndia, CheapSofosbuvirandDaclatasvirOnline, SofosbuvirandDaclatasvirSideEffect, BuySofosbuvirandDaclatasvirPayPal, PurchaseSofosbuvirandDaclatasvironline, SofosbuvirandDaclatasvirreview, SofosbuvirandDaclatasvirsupplierinIndia, SofosbuvirandDaclatasviruses, SofosbuvirandDaclatasvireBay, BuyGenericSofosbuvirandDaclatasvir, BuySofosbuvirandDaclatasvirCheapSofosbuvirandDaclatasvir, BuySovaldidaklinzaOnlineIndia, BuySofosbuvirandDaclatasvironlineovernightshipping, BuySofosbuvirandDaclatasvirinIndia, BuySofosbuvirandDaclatasvirOnlineUK, buySofosbuvirandDaclatasvironlinecheap, isthereaSofosbuvirandDaclatasvir, bestwebsitetobuySovaldidaklinza, genericSofosbuvirandDaclatasvirvs.Sovaldidaklinza, doesgenericSofosbuvirandDaclatasvirwork, SofosbuvirandDaclatasvirvs.Sovaldidaklinzareviews, BuySofosbuvirandDaclatasvironlinePayPal, buySofosbuvirandDaclatasvirfromCanada, SofosbuvirandDaclatasvirCanadapharmacy, CheapestSofosbuvirandDaclatasvir, SofosbuvirandDaclatasvirforsale, SofosbuvirandDaclatasvironlineCanadianpharmacy, DiscountSofosbuvirandDaclatasvir, OrderSofosbuvirandDaclatasvirOnline, buySofosbuvirandDaclatasvironlinesafely, buySofosbuvirandDaclatasvironlinewithMasterCard, buySofosbuvirandDaclatasvironlinewithVisa, buySofosbuvirandDaclatasvironlinewithAmex, buySofosbuvirandDaclatasvironlinewithDiscover, SofosbuvirandDaclatasvirexporterinIndia, SaleSofosbuvirandDaclatasvir, SofosbuvirandDaclatasvirfreeshipping, SofosbuvirandDaclatasvircost, SofosbuvirandDaclatasvir, SofosbuvirandDaclatasvirfastshipping, buySofosbuvirandDaclatasvirSofosbuvirandDaclatasvir, genericformofSovaldidaklinza, genericversionofSovaldidaklinza, Sovaldidaklinzadiscount, wheretobuySofosbuvirandDaclatasvironline, Sovaldidaklinzaonlinepharmacy, SofosbuvirandDaclatasvirbuy, bestplacetobuySofosbuvirandDaclatasvir, buySovaldidaklinzawithbitcoin, buySofosbuvirandDaclatasvirwithbitcoin
Additional Information
ProID 201404072772
Equivalent Brand Sofosbuvir & Daclatasvir
Strength 400mg + 60mg
Generic Name Sofosbuvir & Daclatasvir
Manufacturer Natco Pharma, India
Pharmaceutical Form Tablet/s

レビューを書く

注意: HTMLタグは使用できません!
    悪い           良い
Powered By OpenCartChina

xWIN-win mac 株式会社ヒロタ © 2018