Sofosbuvir is a direct-acting antiviral agent used to treat chronic hepatitis C infections.

It is recommended for the treatment of genotypes 1, 2, 3, and 4 in adults and genotypes 2 and 3 in children aged 12 years of age or more or weighing 35 kgs or more without cirrhosis or with compensated cirrhosis, in combination with other medicines.

Off-label uses of sofosbuvir include:

• Decompensated Cirrhosis, secondary to Chronic hepatitis C genotype 1, 2, 3, & 4.
• Liver transplant patients recipients with Chronic hepatitis C genotype 1, 2, 3, 4, 5, and 6.
• Renal transplant recipients with chronic hepatitis C genotype 2, 3, 5, or 6.

Treatment of Hepatitis C with Ribavirin or Ribavirin and Interferon is not recommended. (AASLD/ IDSA 2017) 

Sofosbuvir dose in Adults:

Chronic Hepatitis C (mono-infection or co-infection with HIV):

Genotype 1:

• Treatment-naive patients without cirrhosis or patients previously treated with peg-interferon and ribavirin (without cirrhosis):
  • 400 mg once daily for 12 weeks in combination with daclatasvir or simeprevir
• Off-label use in patients with decompensated cirrhosis (Child B or C):
  • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin. Treatment duration may be prolonged to 24 weeks in patients who are not eligible for ribavirin therapy.
• Off-label use in Liver transplant recipients without cirrhosis or with compensated cirrhosis (Child Class A):
  • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin or simeprevir with or without ribavirin.

• Genotype 2:

  • Treatment-naive patients or patients previously treated with peg-interferon and ribavirin:
    • 400 mg once daily for 12 weeks in combination with daclatasvir without cirrhosis or for 24 weeks with compensated cirrhosis.
  • Off-label use in patients with decompensated cirrhosis (Child B or C):
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin. Treatment duration may be prolonged to 24 weeks in patients who are not eligible for ribavirin therapy.
  • Off-label use in Liver transplant recipients with or without cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.
  • Renal transplant recipients without cirrhosis or with compensated child class A cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.

• ---

  Genotype 3:

  • Treatment-naive patients or patients previously treated with peg-interferon and ribavirin without cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir.
  • Treatment-naive patients with compensated child class A cirrhosis:
    • 400 mg once daily in combination with daclatasvir with or without ribavirin for 24 weeks.
  • Off-label use in patients with decompensated cirrhosis (Child B or C):
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin. Treatment duration may be prolonged to 24 weeks in patients who are not eligible for ribavirin therapy.
  • Off-label use in Liver transplant recipients with or without cirrhosis including decompensated cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.
  • Renal transplant recipients without cirrhosis or with compensated child class A cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.

• Genotype 4:

  • Off-label use in patients with decompensated cirrhosis (Child B or C):
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin. Treatment duration may be prolonged to 24 weeks in patients who are not eligible for ribavirin therapy.
  • Off-label use in Liver transplant recipients without cirrhosis or with compensated cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin or simeprevir with or without ribavirin for 12 weeks.

• Genotypes 5 and 6:

  • Off-label use in Liver transplant recipients without cirrhosis or with compensated child class A cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.
  • Renal transplant recipients without cirrhosis or with compensated child class A cirrhosis:
    • 400 mg once daily for 12 weeks in combination with daclatasvir and ribavirin.

Sofosbuvir dose in children:

Chronic Hepatitis C (mono-infection or co-infection with HIV):

Treatment-naive patients or treatment-experienced without cirrhosis or with compensated child class A cirrhosis:

• Children 12 years of age or more or weighing 35 kgs or more:

  • Genotype 2:
    • • 400 mg once daily for 12 weeks in combination with ribavirin.
  • Genotype 3:
    • • 400 mg once daily for 24 weeks in combination with ribavirin.

Pregnancy Category C

• Hepatitis C should not be treated before delivery. It is not recommended to treat Hepatitis B during pregnancy.
• Combination therapy with Ribavirin should not be done. Only clinical trials should be conducted for the treatment of hepatitis C during pregnancy with directly acting antiviral drugs.
• Patients who are pregnant should not wait for treatment to be complete before they consider having a baby.

Sofosbuvir during breastfeeding:

• It is unknown whether sofosbuvir can be excreted in breast milk. 
• Manufacturers recommend that you weigh the risks and benefits of breastfeeding.
• Although breastfeeding is not associated with hepatitis B transmission, it is recommended that patients who are co-infected or HIV-positive do not breastfeed.

Sofosbuvir dose in kidney disease:

• eGFR of 30 ml/min/1.73 m2:

  • No dose adjustment is necessary

• eGFR of less than 30 ml/min/1.73 m2 and patients with ESRD on hemodialysis:

  • The manufacturer has not provided any recommendations because the drug has not been studied in this group of patients.

Dose in Liver disease:

• No dose adjustment is required in Liver disease including Child Class B & C cirrhosis. 

Common side effects of sofosbuvir:

• Central nervous system:
  • Fatigue, headache, lethargy, insomnia, irritability, and chills.
• Skin-related side effects:
  • Pruritis and rash
• Gastrointestinal side effects:
  • Nausea, anorexia, and diarrhea.
• Blood-related side effects:
  • Anemia and neutropenia
• Skeletal and neuromuscular effects:
  • Asthenia and myalgias
• Miscellaneous:
  • Fever and flu-like symptoms

Less common side effects include:

• Gastrointestinal & hepatic side effects:
  • increased serum lipase and bilirubin levels.
• Blood-related effects:
  • Thrombocytopenia
• Miscellaneous:
  • Increased serum creatine phosphokinase levels, depression, hypersensitivity reactions

Contraindications to Sofosbuvir:

• Patients with severe allergic reactions or males with female partners may become pregnant.

Warnings and Precautions

• Hepatitis B virus activation (US Boxed Warnings).
• Patients should be tested for Hepatitis B and co-infection. Reactivation or flare-ups of hepatitis B may occur if hepatitis C is treated.
•  Reactivation especially occurs if the patient is on immunosuppressive agents as well.
• Patients with hepatitis B coinfection or reactivation should be closely monitored and treated as soon as possible.
• Most patients will be HBsAg-positive and the HBV DNA levels will rise in their serum leading to fulminant Hepatitis B, hepatic dysfunction, and even death.

Hypoglycemia in patients with Diabetes:

• Sofosbuvir can cause hypoglycemia in diabetic patients after reducing the hepatitis C viral load.
• Patients should be monitored and anti-diabetic medicines may need adjustment because of improvement in glucose metabolism, especially in the first three months of therapy.
• Patients on Amiodarone may experience symptoms of Bradycardia.
• Amiodarone-treated patients may experience severe bradycardia if they are given sofosbuvir.
• This could require a pacemaker to be inserted. Patients on amiodarone may experience fatal cardiac arrest if they take ledipasvir or sofosbuvir.
• If the patient is taking amiodarone, Sofosbuvir shouldn't be used in combination with any other direct-acting antiviral agents. These patients require cardiac monitoring

Sofosbuvir: Drug Interaction

Monitor

• Blood CBC, Liver function tests, and creatinine at baseline and then periodically as indicated.
• Patients on Amiodarone should be on a cardiac monitor for the first 48 hours and then on an outpatient basis for at least two weeks.
• Serum HCV RNA should be monitored at baseline, during treatment, at the end of the treatment and at follow up.
• Hepatitis B surface antigen and core antibodies should be checked prior to initiating therapy with antivirals agents.
• Patients with co-infection should be monitored for a flare-up of Hepatitis B.
• Patients with resolved Hepatitis B should be monitored for reactivation of hepatitis B.
• Diabetic patients should monitor their blood glucose levels because hypoglycemia may occur as a result of altered glucose metabolism after viral suppression.

How to administer?

• Take the drug with or without meals.

Mechanism of action of sofosbuvir:

• Sofosbuvir, a prodrug, is activated by intracellular metabolism.
• It acts directly against viral replication by inhibiting HCV NS5BRNA dependent RNA polymerase.

Metabolism is mainly via the liver

Half-life elimination is 0.4 hours

Time to peak is ~0.5 to 2 hours

Excretion is mostly via the Urine (80%)

International Brands:

• Grateziano
• Gratisovir
• Hepcee
• Hepcinat
• Hepcivir
• Hopforhep
• HopSo
• Myhep
• Sofgen
• Soforal
• Sovaldi
• Soventa

Brands in Pakistan:

• Sovaldi (Ferozesons Ltd)
• Ocvir (Sami pharma)
• Sofomac (Macter Pharma)
• Cure-C (Global Pharma)
• Sofiget (Getz pharma)
• Sofohil (Hilton Pharma)
• Vibrenta (Tabros Pharma)