Elbasvir is a drug approved by the FDA in January 2016[1] for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS3/4A protease inhibitor grazoprevir under the trade name Zepatier, either with or without ribavirin.[2]
Elbasvir is a highly potent and selective NS5A inhibitor of the hepatitis C virus NS5A replication complex.[3] It has only been investigated as a combination product with other complementary hepatitis C antiviral drugs such as grazoprevir and MK-3682, and it is unclear whether elbasvir would show robust antiviral activity if it was administered by itself. Nevertheless, combination products of this type represent the most successful approach yet developed for actually curing hepatitis C, rather than merely slowing the progression of the disease.[4]
Contents
1Side effects
2Interactions
3Pharmacology
3.1Mechanism of action
3.2Pharmacokinetics
4References
Side effects
Side effects have only been assessed in the combination with grazoprevir; see Elbasvir/grazoprevir#Side effects.
Interactions
Elbasvir is degraded by the liver enzyme CYP3A4. Combination with drugs that induce this enzyme, such as efavirenz, carbamazepine or St. John's wort, can lead to ineffectively low plasma levels of elbasvir. Combination with CYP3A4 inhibitors may increase plasma levels.[5]
Pharmacology
Mechanism of action
Further information: Discovery and development of NS5A inhibitors § Mechanism of action
The substance blocks NS5A, a protein necessary for hepatitis C virus replication and assembly.[5]
Pharmacokinetics
Elbasvir reaches peak plasma concentrations three hours after oral intake together with grazoprevir (variation between patients: three to six hours). In hepatitis C patients, steady state concentrations are found after about six days. Plasma protein binding is over 99.9%, mainly to albumin and alpha-1-acid glycoprotein. Part of the substance is oxidised in the liver, largely by the enzyme CYP3A4. The biological half-life is 24 hours on average. Over 90% are excreted via the faeces, and less than 1% via the urine.[5][6]
References
^FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4. January 28, 2016
^Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, et al. (March 2015). "Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial". Lancet. 385 (9973): 1075–86. doi:10.1016/S0140-6736(14)61795-5. PMID 25467591.
^Coburn CA, Meinke PT, Chang W, Fandozzi CM, Graham DJ, Hu B, et al. (December 2013). "Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity". ChemMedChem. 8 (12): 1930–40. doi:10.1002/cmdc.201300343. PMID 24127258.
^Gentile I, Buonomo AR, Zappulo E, Borgia G (July 2014). "Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world?". Expert Review of Anti-Infective Therapy. 12 (7): 763–73. doi:10.1586/14787210.2014.929497. PMID 24918116.
…combination tablet consists of 50 mg elbasvir and 100 mg grazoprevir and is administered once daily with or without food. Prior to administration of elbasvir-grazoprevir, patients with genotype 1a infection …
…relapsed after treatment with a regimen containing an NS5A inhibitor (such as ledipasvir, daclatasvir, elbasvir, or ombitasvir) Throughout this topic, peginterferon refers specifically to peginterferon-alfa …
…r, sofosbuvir-velpatasvir, sofosbuvir-velpatasvir-voxilaprevir, glecaprevir-pibrentasvir, elbasvir-grazoprevir, ombitasvir-paritaprevir-ritonavir with or without dasabuvir, daclatasvir, and simeprevir …
…patients with Child Pugh classes B and C cirrhosis. Elbasvir-grazoprevir – For genotype 4 infection, the fixed-dose combination pill elbasvir-grazoprevir is given once daily for 12 weeks for treatment-naive …
…regimens. As examples, patients with genotype 1a infection should be tested for NS5A RASs if elbasvir-grazoprevir is being considered, and patients with genotype 3 infection who have cirrhosis or prior treatment …
English Journal
Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient.
Chen J, Li Y, Li G, Lei P.
Renal failure. 2020 Nov;42(1)377-380.
Hepatitis C virus (HCV) infection is known to affect long-term patient survivals. Elbasvir/grazoprevir (EBR/GZR) has shown a high cure rate in hemodialysis patients with HCV infection. However, the combination is rarely used in peritoneal dialysis patients. Herein, we report a case of successful tre
Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study.
, W W, J J, J J, h h, .
Journal of chemical information and modeling. 2020 May;().
The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed
Modeling-based response-guided therapy for chronic hepatitis C under glecaprevir/pibrentasvir may identify patients for ultra-short treatment duration.
Dasgupta S, Imamura M, Gorstein E, Nakahara T, Tsuge M, Churkin A, Yardeni D, Etzion O, Uprichard SL, Barash D, Cotler SJ, Dahari H, Chayama K.
The Journal of infectious diseases. 2020 May;().
We recently showed in a proof-of-concept study that real-time modeling-based response-guided therapy (RGT) can shorten hepatitis C virus (HCV) treatment duration with sofosbuvir/velpatasvir, elbasvir/grazoprevir and sofosbuvir/ledipasvir without compromising efficacy, confirming our retrospective mo
… <p>The aim of this retrospective multicenter study was to clarify efficacy and safety of Elbasvir/Grazoprevir for chronic hepatitis C patients with chronic kidney disease (CKD). … Forty-five patients with CKD were administered Elbasvir/Grazoprevir and subjected to this analysis. … This study suggests that Elbasvir/Grazoprevir therapy is effective and safe for genotype 1b chronic hepatitis C patients with CKD.</p> …
Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C, an infectious liver disease caused by infection with hepatitis C virus (HCV). HCV is a single-stranded RNA virus that is ...
Elbasvir is an NS5A inhibitor, preventing hepatitis C viral RNA replication and virion assembly. Median EC50 values range from 0.2 to 3600 pmol/L, based on genotype.