Elbasvir is a drug approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in January 2016 for the treatment of

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

. It was developed by

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

and completed Phase III trials, used in combination with the NS3/ 4A protease inhibitor

grazoprevir Grazoprevir is a drug approved for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS5A replication complex inhibitor elbasvir under the trade name ''Zepatier'', either with ...

under the trade name ''

Zepatier Elbasvir/grazoprevir (trade name Zepatier ) is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir (an inhibitor of hepatitis C virus's NS5A protein) and grazoprevir (an NS3 (HCV), NS3/NS4A, 4A inhibitor). It is used t ...

'', either with or without

ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pegin ...

. Elbasvir is a highly potent and selective NS5A inhibitor of the

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

NS5A Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is deriv ...

replication complex. 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.

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 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. Combination with drugs that induce this enzyme, such as

efavirenz Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlest ...

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

St. John's wort ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...

, can lead to ineffectively low plasma levels of elbasvir. Combination with CYP3A4 inhibitors may increase plasma levels.

Pharmacology

Mechanism of action

The substance blocks

, a protein necessary for hepatitis C

virus replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...

and assembly.

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 Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

is over 99.9%, mainly to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

and alpha-1-acid glycoprotein. Part of the substance is oxidised in the liver, largely by the enzyme CYP3A4. The

biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is 24 hours on average. Over 90% are excreted via the faeces, and less than 1% via the urine. on Zepatier.

References

{{RNA antivirals NS5A inhibitors Carbamates Pyrrolidines Imidazoles