sofosbuvir/velpatasvir

Action and Spectrum

Actions and spectrum: 

sofosbuvir and velpatasvir are two antiviral medications used in combination for the treatment of chronic hepatitis C virus (HCV) infection in adults. Sofosbuvir is nucleotide analogue inhibitor of the HCV NS5B RNA-dependent RNA polymerase, while velpatasvir is an inhibitor of the HCV NS5A protein.

Together, they act to disrupt the replication cycle of the HCV virus, resulting in a decrease in viral load and a higher likelihood of sustained virologic response (SVR). This combination therapy is effective against all genotypes of HCV and has a high cure rate, even in patients with advanced liver disease. It is generally well-tolerated and can be taken orally, which increases adherence to treatment. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Without cirrhosis 

• Fatigue (15%) 
• Headache (22%)

With decompensated cirrhosis 

• Insomnia (11%) 
• Headache 11%) 
• Nausea (15%) 
• Hemoglobin (23%) 
• Anemia (26%) 
• Fatigue (32%)

Frequency not defined 

1-10% 

Without cirrhosis 

• Depression (1%) 
• Increased creatinine kinase (1%) 
• Rash (2%) 
• Lipase increase (3%) 
• Insomnia (5%) 
• Asthenia (5%) 
• Nausea (9%)

With decompensated cirrhosis 

• Increased creatinine kinase (2%) 
• Rash (5%) 
• Hemoglobin (7%) 
• Diarrhea (10%)

Postmarketing Reports 

Cardiac disorders 

Skin and subcutaneous tissue disorders 

Black Box Warning

Black Box Warning:  

There is no black box warning for the combination of sofosbuvir and velpatasvir. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Patients with a history of a previous hypersensitivity reaction to any component of the medication. 
• Concomitant use with drugs that are strong inducers of CYP2B6, CYP2C8, or CYP3A4, as this may result in reduced efficacy of sofosbuvir and velpatasvir. 
• Patients suffering from severe hepatic impairment (Child-Pugh Class C) as the safety and efficacy of the medication have not been established in this population. 

Caution: 

• Hepatitis B virus (HBV) reactivation: Co-administration of sofosbuvir and velpatasvir with or without ribavirin can lead to HBV reactivation in patients who are co-infected with HCV and HBV. Prior to starting treatment with sofosbuvir and velpatasvir, patients should be tested for evidence of current or prior HBV infection. 
• Risk of bradycardia when used with amiodarone: Co-administration of sofosbuvir and velpatasvir with amiodarone can result in severe symptomatic bradycardia. Therefore, patients receiving both drugs should undergo cardiac monitoring. 
• Risk of drug interactions: sofosbuvir and velpatasvir are metabolized by different CYP enzymes, which increases the potential for drug interactions. Patients should inform their healthcare provider of all medications they are taking before starting treatment with sofosbuvir and velpatasvir. 
• Renal impairment: Dose adjustment of sofosbuvir and velpatasvir is necessary in patients with severe renal impairment, including those requiring dialysis. 
• Pregnancy and lactation: The efficacy and safety of sofosbuvir and velpatasvir is established in pregnant or breastfeeding women.

Comorbidities: 

• Liver disease: sofosbuvir and velpatasvir are primarily used to treat chronic HCV infection, which can lead to liver damage and cirrhosis. Patients with more advanced liver disease may require additional monitoring and dose adjustments. 
• Renal impairment: Both sofosbuvir and velpatasvir are primarily eliminated by the kidneys, so patients with renal impairment may require dose adjustments or more frequent monitoring. 
• HIV coinfection: Patients with HIV and HCV coinfection may require additional monitoring and drug interactions need to be considered before prescribing these medications. 
• Cardiovascular disease: Patients with a history of cardiovascular disease may require additional monitoring as some studies have shown with the use of sofosbuvir and velpatasvir there is an increased risk of cardiovascular events. 
• Pregnancy and breastfeeding: The safety of sofosbuvir and velpatasvir during pregnancy and breastfeeding has not been established. Therefore, caution should be exercised before prescribing these medications to pregnant or breastfeeding women. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category B 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the 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 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: 

• sofosbuvir and velpatasvir are antiviral drugs used in to treat the chronic hepatitis C virus (HCV) infection in adults. 
• Sofosbuvir is a prodrug that is metabolized to its active form, GS-461203, which acts as an inhibitor of the HCV nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase, preventing the viral replication. 
• velpatasvir is an HCV NS5A inhibitor, which prevents the assembly and release of infectious HCV virions. 

The combination of these drugs sofosbuvir and velpatasvir is highly effective in the treating of all genotypes of HCV infection, with cure rates of over 90%.  

Pharmacodynamics: 

sofosbuvir and velpatasvir are antiviral medications used to treat chronic hepatitis C virus (HCV) infections. Sofosbuvir is a nucleotide analog inhibitor of the HCV RNA polymerase, while velpatasvir is a potent and selective inhibitor of the HCV NS5A protein. 

Sofosbuvir works by blocking the activity of the HCV RNA polymerase enzyme, which is essential for the virus to replicate and spread. Velpatasvir, on the other hand, interferes with the assembly and release of the virus particles by targeting the NS5A protein. The combination of sofosbuvir and velpatasvir has a synergistic effect against HCV, as they target different steps of the viral replication cycle.  

Pharmacokinetics: 

Absorption 

sofosbuvir is rapidly absorbed and converted to its active form, GS-461203, while Velpatasvir is slowly absorbed. The combination tablet is designed to enhance the absorption of Velpatasvir. 

Distribution 

sofosbuvir and Velpatasvir are highly protein-bound, with >99% bound to plasma proteins. 

Metabolism 

sofosbuvir is metabolized to its active metabolite, GS-461203, primarily by the liver enzyme aldehyde oxidase (AO) and to a lesser extent by cytochrome P450 (CYP) enzymes. Velpatasvir is minimally metabolized by CYP enzymes. 

Elimination and excretion 

sofosbuvir and GS-461203 are primarily eliminated in the urine. Velpatasvir is eliminated through a combination of biliary excretion and metabolism. 

The half-life of Sofosbuvir is approximately 0.5 to 2 hours, while the half-life of Velpatasvir is approximately 15 hours. The combination tablet is designed for once-daily dosing. 

Adminstartion

Administration: 

sofosbuvir/Velpatasvir is an oral medication that comes in the form of tablets. It is typically taken once a day with or without food. The exact dosage and duration of treatment depend on the individual’s condition and medical history, as well as other factors such as viral genotype and prior treatment history.

It is important to follow the prescribing doctor’s instructions carefully and to complete the full course of treatment to achieve the best possible outcomes. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sofosbuvir and velpatasvir 

Pronounced: [ soe-FOS-bue-vir-and-vel-PAT-as-vir ]  

Why do we use sofosbuvir and velpatasvir? 

sofosbuvir/Velpatasvir is an antiviral medication used to treat chronic hepatitis C virus in adults. The medication is indicated for the treatment of all six major genotypes of HCV infection.

sofosbuvir/Velpatasvir is often used in combination with ribavirin and/or other medications depending on the specific genotype of the virus and the patient’s medical history.

The medication works by interfering with the replication of the hepatitis C virus, ultimately leading to its eradication from the body. Treatment with sofosbuvir/Velpatasvir is typically administered for a period of 12 weeks.