ledipasvir

Action and Spectrum

Actions and spectrum 

Ledipasvir which inhibits the Hepatitis C Virus (HCV) NS5A protein that is required for RNA replication and HCV virions assembly. Although its exact mechanism of action is not completely known, it is thought to prevent NS5A, one of the proteins which might stop viral production. 

Drug Interaction

Adverse Reaction

Adverse Reaction 

• Nausea
• Fatigue
• Diarrhea
• Insomnia

Black Box Warning

Black box warning 

None 

Contraindication / Caution

Contraindications/caution

• Hepatic impairment
• Renal impairment

Pregnancy / Lactation

Pregnancy/Lactation 

Pregnancy warnings: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.   

Pregnancy Category: B 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy Categories:   

Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the 1st trimester or in the 3rd trimester.   

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.   

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.   

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.   

Category N: There is no data available for the drug under this category.    

Pharmacology

Pharmacology 

It is a highly selective agent that binds directly to the HCV non-structural protein 5A (NS5A), which plays the pivotal role for viral RNA replication as well as the formation of new HCV virions (virions acquisition). Ledipasvir cancels the functions of NS5A where it required for viral replication, thereby decreasing rate of viral replication in the body. 

Pharmacodynamics 

Ledipasvir which is a direct-acting antiviral agent (DAA) targets hepatitis C virus (HCV). This study administered ledipasvir twice daily in a dose of 120 mg (2.67 times the maximum recommended dosage). At this dose, ledipasvir did not prolong the QTc interval significantly in any clinically relevant way. 

Pharmacokinetics: 

Absorption 

The oral administration of ledipasvir results in its peak plasma concentration (Cmax) of 323 ng/mL in around 4 to 4. 5 hours. 

Distribution 

More than 98% of the drug is bound to the plasma proteins. 

Metabolism 

Human CYP1A2, CYP2C8 and CYP3A4 enzymes did not even metabolize ledipasvir in detectable amounts, according to an in vitro study. It is revealed through research that delayed oxidative metabolism occurs through an unknown phenomenon. The systemic exposure in >98% of occurrence was to the parent medicine of ledipasvir after a single 90 mg [14C]-ledipasvir dosage. The most common unaltered form ledipaser found in feces is ledipasvir. 

Elimination/Excretion 

Within 8 days after the single oral dose of 90 mg 14C-ledipasvir the mean total recovery was 87% and the contribution from the feces was around 86% of the total recovered quantity. The unmetabolized ledipasvir in feces achieved an average of 70% of the administered dose, while the oxidative metabolite M19 only accounted for a mean of 2%. These revealed that the main way of excretion of the drug was through the bile canals and the minor way was through the kidneys about 1%. 

Adminstartion

Administration 

It is administered orally 

Patient Information Leaflet

Patient Information Leaflet 

Generic Name: ledipasvir 

Why do we use ledipasvir? 

Ledipasvir is a direct-acting antiviral medication along with other antiviral agents. It is used in the treatment of Hepatitis C infections.