daclatasvir

Action and Spectrum

Actions and Spectrum: 

daclatasvir is a direct-acting antiviral (DAA) medication primarily used to treat chronic hepatitis C (HCV) infections. Its mechanism of action involves targeting a specific protein essential for the replication of HCV. 

The main target of daclatasvir is the HCV nonstructural protein NS5A. NS5A is involved in multiple stages of the HCV replication cycle and plays a crucial role in viral RNA replication, assembly, and release. Daclatasvir binds to NS5A and inhibits its function, thereby disrupting the replication of the virus. 

By blocking NS5A, daclatasvir effectively inhibits HCV replication and reduces the viral load in infected individuals. This antiviral activity helps to suppress the progression of liver disease associated with chronic HCV infection. 

Regarding the spectrum of activity, daclatasvir is highly specific to HCV and has limited or no activity against other viruses. It is primarily effective against HCV genotypes 1-6, the significant genotypes found worldwide. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache  

Anemia  

Fatigue  

Nausea  

1-10% 

Insomnia  

Increased serum lipase  

Drowsiness 

Diarrhea 

Post-marketing reports 

Reactivation of HBV 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: daclatasvir should not be used in individuals with known hypersensitivity or allergy to daclatasvir or its components. 
• Concomitant use with certain medications: daclatasvir is metabolized primarily by the enzyme CYP3A4. Therefore, coadministration with potent inducers of CYP3A4, such as rifampin, St. John’s wort, and carbamazepine, is contraindicated. These medications can significantly decrease the plasma concentrations of daclatasvir, reducing its effectiveness. 
• Concomitant use with certain medications that are also HCV antivirals: daclatasvir is not recommended to be used concomitantly with other HCV antiviral medications, such as simeprevir or sofosbuvir/velpatasvir/voxilaprevir combination therapy.  

Caution: 

• Hepatic impairment: daclatasvir should be used cautiously in individuals with moderate to severe hepatic impairment.  
• Renal Impairment: Data on the use of daclatasvir in patients with severe renal impairment or end-stage renal disease are limited.  
• Co-infection with HIV: For individuals co-infected with both HCV and HIV, daclatasvir should be combined with HIV antiretroviral therapy (ART) regimens that are compatible and do not have significant drug-drug interactions. 
• Resistance Testing: Before initiating daclatasvir treatment, resistance testing should be considered, especially in patients with a prior HCV treatment or those infected with specific HCV genotypes associated with higher resistance rates. 

Pregnancy / Lactation

Pregnancy consideration: daclatasvir is predicted to pass the placenta. Patients who are pregnant or whose companions are pregnant are not permitted to use this medication. ribavirin and daclatasvir have known teratogenic effects and can cause severe congenital disabilities. 

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

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

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

Pharmacology

Pharmacology: 

daclatasvir exerts its antiviral effect by targeting HCV’s nonstructural protein 5A (NS5A). NS5A is a multifunctional protein involved in various stages of the HCV replication cycle. It binds to NS5A and disrupts its function, inhibiting viral RNA replication, assembly, and release. By interfering with NS5A, daclatasvir effectively suppresses HCV replication and reduces the viral load in infected individuals. 

Pharmacodynamics:  

daclatasvir is a direct-acting antiviral (DAA) medication that targets the nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV). By binding to NS5A, daclatasvir disrupts its function and inhibits viral replication. daclatasvir exhibits potent antiviral activity against HCV, reducing the viral load and suppressing viral replication. It is effective against multiple genotypes of HCV, although susceptibility may vary across genotypes.

Combination therapy with daclatasvir and other DAAs is commonly used for optimal treatment outcomes, enhancing efficacy and minimizing the risk of drug resistance. Successful treatment with daclatasvir can reduce liver inflammation and fibrosis associated with chronic HCV infection. Achieving sustained virologic response (SVR) with daclatasvir is associated with long-term improvements in liver function and a decreased risk of liver-related complications. 

Pharmacokinetics: 

Absorption 

The drug reaches its maximum concentration in the plasma within 2 hours after administration.  

Distribution 

Volume of distribution at steady state (Vdss): 47 L. Approximately 99% of the drug is bound to plasma proteins.  

Metabolism 

The primary metabolic pathway for the drug is via the enzyme CYP3A4.  

Elimination and Excretion 

The drug has an elimination half-life of approximately 12 to 15 hours. The drug is primarily excreted through the feces (88%), with approximately 53% of the dose being eliminated unchanged. A smaller portion is excreted in the urine (6.6%), primarily unchanged. 

Adminstartion

Administration: 

Oral administration 

Give with or without a meal 

Patient Information Leaflet

Patient information leaflet 

Generic Name: daclatasvir 

Why do we use daclatasvir? 

daclatasvir is primarily used to treat chronic hepatitis C (HCV) infection. It is indicated for combination with other antiviral medications as part of a comprehensive treatment regimen. Here are some key uses of daclatasvir: 

• Treatment-Naive Patients: daclatasvir, combined with other HCV antiviral agents, treats individuals with chronic HCV infection who have not received previous treatment (treatment-naive). 
• Treatment-Experienced Patients: daclatasvir, in combination with other HCV antiviral agents, is also used to treat individuals with chronic HCV infection who have previously received treatment (treatment-experienced), including those who have not achieved a sustained virologic response (SVR) or relapsed after prior therapy. 
• Genotype-Specific Treatment: daclatasvir can treat HCV infection across genotypes (1-6). The specific combination regimen and duration of treatment may vary depending on the genotype of the HCV infection and the individual patient’s characteristics. 
• Special Populations: daclatasvir, in combination with other antiviral agents, is also used in special populations, such as individuals co-infected with HCV and HIV and patients with compensated or decompensated cirrhosis.