Ledipasvirum

Ledipasvirum Uses, Dosage, Side Effects, Food Interaction and all others data.

Ledipasvirum is a direct acting antiviral (DAA) 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 categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as ledipasvir. More specifically, ledipasvir is an inhibitor of the Hepatitis C Virus (HCV) Non-Structural Protein 5A (NS5A), which is required for viral RNA replication and assembly of HCV virions. Although its exact mechanism of action is unknown, it is postulated to prevent hyperphosphorylation of NS5A which is required for viral protein production. It is effective against genotypes 1a, 1b, 4a, and 5a and with a lesser activity against genotypes 2a and 3a of HCV. Ledipasvirum and other direct acting antivirals are very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance . This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend ledipasvir as a first line therapy option in combination with sofosbuvir for the treatment of HCV genotypes 1a, 1b, 4, 5, and 6 . Treatment with ledipasvir is used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality . Treatment with direct acting antivirals such as ledipasvir is associated with very minimal side effects, with the most common being headache and fatigue . Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects .

Since 2014, ledipasvir has been available as a fixed dose combination product with sofosbuvir (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without ribavirin depending on the level of liver damage or cirrhosis . When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment . Its use has also proven successful in the treatment of HCV in patients co-infected with HIV .

Ledipasvirum
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Ledipasvirum
Generic	Ledipasvir
Ledipasvir Other Names	Ledipasvir, Lédipasvir, Ledipasvirum
Type
Formula	C₄₉H₅₄F₂N₈O₆
Weight	Average: 888.9999 Monoisotopic: 888.41343791
Protein binding	Ledipasvir is >99.8% bound to human plasma proteins .
Groups	Approved
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Ledipasvirum is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.

When used in combination with the antiviral medication sofosbuvir as the commercially available product Harvoni, ledipasvir is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without ribavirin depending on the level of liver damage or cirrhosis . Its use has also proven successful in the treatment of HCV in patients co-infected with HIV .

Ledipasvirum is also used to associated treatment for these conditions: Chronic Hepatitis C Genotype 1, Chronic hepatitis C genotype 4, Chronic hepatitis C genotype 5, Genotype 6 chronic hepatitis C infection

How Ledipasvirum works

Ledipasvirum is an inhibitor of the Hepatitis C Virus (HCV) NS5A protein required for viral RNA replication and assembly of HCV virions. Although its exact mechanism of action is unknown, it is postulated to prevent hyperphosphorylation of NS5A which is required for viral production.

Toxicity

There is very little toxicity associated with the use of ledipasvir in combination products. The most common adverse reactions are headache and fatigue.

Food Interaction

Avoid St. John's Wort. This herb induces PGP and may reduce the serum concentration of ledipasvir.
Take separate from antacids. Take at least 4 hours before or after antacids.
Take with or without food.

Elimination Route

When given orally, ledipasvir reaches its maximum plasma concentration in about 4 to 4.5 hours with a maximum concentration (Cmax) of 323 ng/mL .

Half Life

The median terminal half-life of ledipasvir is 47 hours .

Elimination Route

Following a single 90 mg oral dose of [14C]-ledipasvir, mean total recovery of the [14C]-radioactivity in feces and urine was approximately 87%, with most of the radioactive dose recovered from feces (approximately 86%). Unchanged ledipasvir excreted in feces accounted for a mean of 70% of the administered dose and the oxidative metabolite M19 accounted for 2.2% of the dose. These data indicate that biliary excretion of unchanged ledipasvir is a major route of elimination, with renal excretion being a minor pathway (approximately 1%) .