sofosbuvir

Action and Spectrum

Actions and Spectrum: 

sofosbuvir is a medication used to treat chronic hepatitis C (HCV) infection. Its mechanism of action involves inhibiting the HCV RNA polymerase enzyme, which is essential for viral replication. Specifically, sofosbuvir is an analog nucleotide inhibitor metabolized to its active form (sofosbuvir triphosphate) within hepatocytes.

Once activated, it is incorporated into the HCV RNA strand during replication and causes chain termination, ultimately preventing further viral replication. sofosbuvir has a broad spectrum of activity against all six genotypes of HCV and is often used with other direct-acting antiviral agents (DAAs) to increase its efficacy. It is generally well-tolerated and has a high cure rate, making it a preferred treatment option for HCV infection 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Sofosbuvir plus ribavarin (12 weeks) 

Fatigue (24%) 

Nausea (11%)  

Insomnia (38%) 

Headache (15%) 

Pruritus (22%) 

Sofosbuvir plus ribavarin (24 weeks) 

Insomnia (30%) 

Headache Fatigue (16%) 

Pruritus (12%)  

Nausea (27%) 

Asthenia (21%) 

Diarrhea(30%) 

Sofosbuvir plus ribavirin plus peg-interferon(12 weeks) 

Decreased appetite (14%) 

Irritability (18%) 

Diarrhea (17%) 

Myalgia (34%) 

Insomnia (12%) 

Neutropenia (16%) 

Pyrexia (36%) 

Nausea (59%) 

Headache (17%) 

Influenza-like illness (17%) 

Anemia (21%) 

Rash (18%) 

Chills (13%)  

Pruritus (25%) 

Fatigue(25%) 

Sofosbuvir plus ribavirin plus peg-interferon(24 weeks) 

Decreased appetite (14%) 

Irritability (18%) 

Diarrhea (17%) 

Myalgia (34%) 

Insomnia (12%) 

Neutropenia (16%) 

Pyrexia (36%) 

Nausea (59%) 

Headache (17%) 

Influenza-like illness (17%) 

Anemia (21%) 

Rash (18%) 

Chills (13%)  

Pruritus (25%) 

Fatigue(25%) 

1-10% 

Sofosbuvir plus ribavarin (12 weeks) 

Diarrhea (2%) 

Influenza-like sickness (6%) 

Rash (6%) 

Irritability (9%) 

Myalgia (10%)  

Decreased appetite (10%) 

Asthenia (3%) 

Pyrexia (4%) 

Anemia (6%) 

Chills (8%) 

Sofosbuvir plus ribavarin (24 weeks) 

Irritability (6%) 

Chills (4%) 

Myalgia (9%) 

Decreased appetite (9%) 

Anemia (6%) 

Pyrexia (2%) 

Influenza-like sickness (6%) 

Rash (10%)  

<1% 

Neutropenia 

Severe depression 

Pancytopenia 

Black Box Warning

Black box warning: 

The U.S. Food and Drug Administration (FDA) recommends testing all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct-acting antivirals (DAAs).

This is because reactivation of HBV has been reported in patients coinfected with both HCV and HBV who were undergoing or had completed treatment with DAAs and were not receiving HBV antiviral therapy 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: It is contraindicated in patients with a known hypersensitivity to sofosbuvir or any of its components 
• Pregnancy: It is contraindicated in pregnancy as it may cause harm to the developing fetus. Women of childbearing potential should use effective contraception during and for six months after treatment with sofosbuvir 
• Concomitant use with certain medications: It may interact with certain medications, such as amiodarone, which can increase the risk of severe slowing of the heart rate. Therefore, the concomitant use of sofosbuvir with amiodarone or other drugs that can slow the heart rate is contraindicated 
• Severe renal impairment: It is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min) as it has not been studied in this population, and its safety and efficacy have not been established 

Caution: 

• Hepatitis B virus (HBV) coinfection: As previously mentioned, HCV and HBV coinfection patients should be monitored closely for HBV reactivation during and after treatment with sofosbuvir 
• Renal impairment: It should be used cautiously in patients with mild to moderate renal impairment as it is primarily excreted through the kidneys. Dose adjustments may be necessary for these patients 
• Drug interactions: It may interact with other medications, including certain antiretroviral drugs, which can affect the levels of sofosbuvir in the body 
• Risk of bradycardia: It has been associated with bradycardia (slow heart rate), mainly when combined with amiodarone or other drugs that can slow the heart rate. Patients receiving these drugs concomitantly with sofosbuvir should be monitored closely for cardiac effects 
• Risk of hepatitis flare: In rare cases, treatment with sofosbuvir may lead to hepatitis flare, particularly in patients with advanced liver disease or those who have previously undergone liver transplantation 

Pregnancy / Lactation

Pregnancy consideration: It is contraindicated in pregnancy as it may cause harm to the developing foetus 

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

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 available 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: 

sofosbuvir is a direct-acting antiviral drug (DAA) used to treat hepatitis C (HCV) infection. It works by inhibiting the activity of the HCV NS5B polymerase, an enzyme necessary for viral replication. 

sofosbuvir is a prodrug, which means it is inactive when taken orally and must be metabolized by the liver to its active form. Once inside the liver cells, sofosbuvir is converted to its active metabolite, GS-461203, which is then incorporated into the growing HCV RNA chain, resulting in chain termination and inhibition of viral replication. 

Pharmacodynamics: 

The pharmacodynamics of sofosbuvir involves its effects on the replication of the hepatitis C virus (HCV) and the resulting reduction in HCV RNA levels in the blood 

sofosbuvir works by inhibiting the activity of the HCV NS5B polymerase, which is responsible for viral RNA replication. The active metabolite of sofosbuvir is incorporated into the growing HCV RNA chain, causing chain termination and inhibition of viral replication. This leads to a reduction in HCV RNA levels in the blood 

The pharmacodynamics of sofosbuvir has been demonstrated in multiple clinical trials. In these trials, sofosbuvir effectively reduced HCV RNA levels in the blood and achieved sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment. SVR is considered a cure for HCV infection. 

Pharmacokinetics: 

Absorption 

Peak plasma time: 0.5-2 hours (sofosbuvir); 2-4 hours (metabolite GS-331007).The bioavailability of sofosbuvir is approximately 92%, indicating high oral absorption. The administration of sofosbuvir with food does not significantly affect its absorption.  

Distribution 

It is highly protein-bound in plasma, with 61-65% bound to plasma proteins. The distribution of the active metabolite GS-331007 is minimal.  

Metabolism 

sofosbuvir is primarily metabolized in the liver to its active metabolite, GS-331007, by hepatic enzymes. sofosbuvir and its active metabolite are not substrates or inhibitors of CYP enzymes, indicating low potential for drug interactions. sofosbuvir is a substrate for P-gp transporter and breast cancer resistance protein, while the active metabolite GS-331007 is a substrate for P-gp transporter only  

Elimination and Excretion 

sofosbuvir and its active metabolite are primarily eliminated via the renal route. The elimination half-life of sofosbuvir is approximately 0.4 hours, while the elimination half-life of the active metabolite GS-331007 is approximately 27 hours. Approximately 78% of the administered dose of sofosbuvir is excreted in the urine as the active metabolite GS-331007, while only 3.5% of the administered dose is excreted as unchanged sofosbuvir 

Adminstartion

Administration: 

Oral Pellets 

• Avoid chewing pellets. 
• Pour one spoonful of nonacidic soft food (such as pudding, chocolate syrup, mashed potatoes, or ice cream) at or below room temperature on top of the pellets if they are delivered with food. 
• To prevent a bitter aftertaste, take the pellets within 30 minutes of gently combining them with food and drink the entire contents without chewing 

Oral Administration: 

Tale with or without meals 

Storage: 

Tablets: Keep below 30 degrees Celsius; use the original bottle. 

Oral pellet packets: Keep 30°C below; if packet seal is broken or damaged, do not use 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sofosbuvir 

Pronounced: [ soe-FOS-bue-vir ] 

Why do we use sofosbuvir? 

It is a direct-acting antiviral (DAA) medication used to treat chronic hepatitis C virus (HCV) infection in adults. It is indicated for treating HCV genotypes 1, 2, 3, 4, 5, and 6, alone or in combination with other DAAs 

sofosbuvir effectively treats chronic HCV infection, achieving high cure rates with shorter treatment duration and fewer side effects compared to older interferon-based treatments. It is generally prescribed as part of combination therapy with other DAAs, such as ledipasvir, velpatasvir, or daclatasvir