HEPATITIS C TREATMENT









Genotype 1
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Harvoni® (sofosbuvir + ledipasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and post-liver transplant
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Viekira Pak™ (ombitasvir + paritaprevir + dasabuvir + ritonavir) - no cirrhosis, Child-Pugh A, and post-liver transplant
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A
  • Zepatier™ (elbasvir + grazoprevir) - no cirrhosis and Child-Pugh A
Genotype 2
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Sofosbuvir (Sovaldi®) + ribavirin - no cirrhosis and Child-Pugh A
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A
Genotype 3
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Sofosbuvir (Sovaldi®) + ribavirin - no cirrhosis and Child-Pugh A
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A
Genotype 4
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Harvoni® (sofosbuvir + ledipasvir) ± ribavirin - no cirrhosis, Child-Pugh A, and post-liver transplant
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Zepatier™ (elbasvir + grazoprevir) - no cirrhosis and Child-Pugh A
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A
Genotype 5
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Harvoni® (sofosbuvir + ledipasvir) ± ribavirin - no cirrhosis and Child-Pugh A
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A
Genotype 6
  • Epclusa® (sofosbuvir + velpatasvir) ± ribavirin - no cirrhosis, cirrhosis (Child-Pugh A,B,C), and liver transplant
  • Harvoni® (sofosbuvir + ledipasvir) ± ribavirin - no cirrhosis or Child-Pugh A
  • Mavyret® (glecaprevir + pibrentasvir) - no cirrhosis, Child-Pugh A, and liver or kidney transplant recipients
  • Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir) - retreatment in no cirrhosis and Child-Pugh A



Epclusa® (sofosbuvir + velpatasvir)
Dosage form

Dosing
  • Previous treatment with regimens containing PegIFN/RBV with or without an HCV NS3/4A PI (boceprevir, simeprevir, or telaprevir)
Epclusa treatment regimens for GT 1, 2, 3, 4, 5, and 6
Patient population Treatment
Treatment-naïve and treatment-experienced with no cirrhosis or Child-Pugh A Epclusa for 12 weeks
Treatment-naïve and treatment-experienced with Child-Pugh B or C Epclusa + weight-based ribavirin for 12 weeks
Liver transplant recipients who are treatment-naïve or treatment-experienced with no cirrhosis or Child-Pugh A Epclusa for 12 weeks
Mechanism of action Drug interactions See Epclusa for a complete review
Harvoni® (sofosbuvir + ledipasvir)
Dosage forms

Dosing
  • Previous treatment with regimens containing PegIFN/RBV with or without an HCV NS3/4A protease inhibitor
  • Ribavirin dosing should be weight-based
Harvoni treatment regimens
HCV GT Patient population Regimen
1
  • Treatment-naïve without cirrhosis, baseline viral load < 6 million IU/ml
May consider Harvoni for 8 weeks
  • Treatment-naïve without cirrhosis or with Child-Pugh A
Harvoni for 12 weeks
  • Treatment-experienced without cirrhosis
Harvoni for 12 weeks
  • Treatment-experienced with Child-Pugh A
Harvoni for 24 weeks
Harvoni + ribavirin for 12 weeks can also be considered
  • Treatment-naïve and treatment-experienced with Child-Pugh B or C
Harvoni + ribavirin for 12 weeks
  • Treatment-naïve and treatment-experienced post-liver transplant without cirrhosis or with Child-Pugh A
Harvoni + ribavirin for 12 weeks
4
  • Treatment-naïve and treatment-experienced without cirrhosis or with Child-Pugh A
Harvoni for 12 weeks
  • Treatment-naïve and treatment-experienced post-liver transplant without cirrhosis or with Child-Pugh A
Harvoni + ribavirin for 12 weeks
5
  • Treatment-naïve and treatment-experienced without cirrhosis or with Child-Pugh A
Harvoni for 12 weeks
5
  • Treatment-naïve and treatment-experienced without cirrhosis or with Child-Pugh A
Harvoni for 12 weeks

Mechanism of action Drug interactions See Harvoni for a complete review
Mavyret® (glecaprevir + pibrentasvir)
Dosage forms

Dosing
Treatment-naïve patients
HCV GN No cirrhosis Child-Pugh A
1,2,3,4,5, and 6 8 weeks 8 weeks

  • PRS = Prior treatment with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir
  • In trials, prior NS5A inhibitor treatment included ledipasvir and daclatasvir
  • In trials, prior NS3/4A PI treatment included simeprevir, boceprevir, or telaprevir
Treatment-experienced patients
HCV GN Previous treatment No cirrhosis Child-Pugh A
1 An NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor 16 weeks 16 weeks
1 An NS3/4A protease inhibitor without prior treatment with an NS5A inhibitor 12 weeks 12 weeks
1, 2, 4, 5, 6 PRS 8 weeks 12 weeks
3 PRS 16 weeks 16 weeks

  • PRS = Prior treatment with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir
  • In trials, prior NS5A inhibitor treatment included ledipasvir and daclatasvir
  • In trials, prior NS3/4A PI treatment included simeprevir, boceprevir, or telaprevir
Liver or kidney transplant recipients
HCV GN Previous treatment Duration
1, 2, 3, 4, 5, 6 None 12 weeks
1 NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor 16 weeks
3 PRS 16 weeks

Mechanism of action Drug interactions See Mavyret for a complete review
Sovaldi® (Sofosbuvir)
Dosage forms Dosing
  • Ribavirin dosing should be weight-based
  • Previous treatment with interferon-based regimen with or without ribavirin
Sofosbuvir treatment regimens in adults
HCV GT Patient population Regimen
1
  • Treatment-naïve without cirrhosis or Child-Pugh A
Sofosbuvir + PegIFN + RBV for 12 weeks
2
  • Treatment-naïve and treatment-experienced without cirrhosis or with Child-Pugh A
Sofosbuvir + RBV for 12 weeks
  • See Epclusa for other HCV GT 2 regimens with sofosbuvir
3
  • Treatment-naïve and treatment-experienced without cirrhosis or with Child-Pugh A
Sofosbuvir + RBV for 24 weeks
  • See Epclusa for other HCV GT 3 regimens with sofosbuvir
4
  • Treatment-naïve without cirrhosis or Child-Pugh A
Sofosbuvir + PegIFN + RBV for 12 weeks
  • See Vosevi for retreatment of GT 1, 2, 3, 4, 5, and 6

Mechanism of action Drug interactions See sofosbuvir for a complete review
Viekira Pak™ (ombitasvir + paritaprevir + dasabuvir + ritonavir)
Dosage forms Dosing
  • Treatment-naïve patients and patients who were prior PegIFN partial responders or relpasers may be treated with 12 weeks of therapy
  • Reference [1]
Viekira Pak Treatment Regimens
Patient population Treatment Duration
GT 1a without cirrhosis Viekira Pak + Ribavirin 12 weeks
GT 1a with Child-Pugh A Viekira Pak + Ribavirin 24 weeks
GT 1b without cirrhosis or Child-Pugh A Viekira Pak 12 weeks
Liver transplant with Metavir ≤ 2 (GT 1a or 1b) Viekira Pak + Ribavirin 24 weeks
Mechanism of action Drug interactions See Viekira Pak for a complete review
Vosevi™ (sofosbuvir + velpatasvir + voxilaprevir)
Dosage forms Dosing
FDA-approved indications
Mechanism of action Drug interactions See Vosevi for a complete review
Zepatier™ (elbasvir + grazoprevir)
Dosage forms Dosing
  • NS5A polymorphisms affect response to Zepatier. See Zepatier for more.
  • PI = boceprevir, simeprevir, or telaprevir
  • Ribavirin dosing is weight-based (regimen 2)
Zepatier treatment regimens
Patient Treatment Duration
GT 1a: Treatment-naïve or PegIFN / Ribavirin-experienced without baseline NS5A polymorphisms Zepatier 12 weeks
GT 1a: Treatment-naïve or PegIFN / Ribavirin-experienced with baseline NS5A polymorphisms Zepatier + ribavirin 16 weeks
GT 1b: Treatment-naïve or PegIFN / Ribavirin-experienced Zepatier 12 weeks
GT 1a or 1b: PegIFN / Ribavirin / PI-experienced Zepatier + ribavirin 12 weeks
GT 4: Treatment-naïve Zepatier 12 weeks
GT 4: PegIFN / Ribavirin-experienced Zepatier + ribavirin 16 weeks

Mechanism of action Drug interactions See Zepatier for a complete review

















Before treatment
Check anytime before start of therapy
  • Hepatitis C genotype
  • Hepatitis C viral load
Baseline labs (within 12 weeks of starting therapy)
  • Complete blood cell count including platelets (CBC)
  • Liver function tests
  • INR
  • CrCl or GFR
  • Pregnancy test - female patients of childbearing potential whose regimens will include ribavirin (see ribavirin monitoring below)
  • Hepatitis B screening - HBsAg, Anti-HBs, and Anti-HBc (see hepatitis B serology for more)
  • HIV
During treatment
Check the following after 4 weeks of therapy and as clinically indicated
  • Complete blood cell count including platelets (CBC) - more frequent monitoring may be required in regimens that include ribavirin (see ribavirin below for more)
  • Liver function tests (see ALT elevations below)
  • CrCl or GFR
Check a HCV viral load after 4 weeks of therapy and 12 weeks after the completion of therapy
  • If viral load is detectable at 4 weeks, recheck in 2 weeks. If viral load increases by > 10-fold (> 1 log10IU/mL) from baseline at week 6 or thereafter, discontinue treatment.
  • Successful treatment of HCV is defined as undetectable viral load by highly sensitive polymerase chain reaction assay (lower limit of detection <12 IU/mL) at 12 weeks after the completion of therapy. Risk of relapse from the original infection after successful treatment is < 1%.
Patients receiving Viekira Pak (ombitasvir, paritaprevir, ritonavir ± dasabuvir) with Child-Pugh A
  • Check liver function tests at 2 and 4 weeks after the start of therapy and as clinically indicated thereafter
  • Patients with Child-Pugh A should be assessed for clinical signs of decompensated liver disease (eg, ascites, encephalopathy, or serum bilirubin > 3 mg/dL)
  • Discontinue medication if signs develop. See Viekira Pak for more.
Patients receiving Zepatier (elbasvir + grazoprevir)
  • Check liver function tests at 8 weeks after the start of therapy. If patients are receiving 16 weeks of therapy, check again at 12 weeks.
  • See Zepatier for more
ALT elevations
For a 10-fold increase in ALT at anytime during therapy
  • Discontinue therapy
For an increase in ALT less than 10-fold with symptoms of hepatitis
  • Discontinue therapy
  • Symptoms of hepatitis include any weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or INR
For an increase in ALT less than 10-fold and no symptoms of hepatitis
  • Recheck LFTs at 2 week intervals. If levels remain persistently elevated, consider stopping therapy. [2]
Ribavirin monitoring
Test of cure
  • Successful treatment of HCV is defined as undetectable viral load by highly sensitive polymerase chain reaction assay (lower limit of detection <12 IU/mL) at 12 weeks after the completion of therapy. Risk of relapse from the original infection after successful treatment is < 1%.
  • Liver function tests should also be checked at the same time to confirm normalization