1. Dosage
1.1. Adults
Direct acting antivirals (DAA) for hepatitis are FDA-indicated for treatment of chronic infections caused by hepatitis C virus (HCV). Individual agents have varying FDA indications and treatment durations based on genotype (1-6), subtype (1a vs. 1b), liver function, HIV co-infection and/or previous treatment history1.
Table 1 provides DAA information for treatment naïve patients with or without cirrhosis.
Drug Name | Dosage Form/Strength | Treatment Indication | Duration and Coadministration | Maximum Recommended Dosage |
---|---|---|---|---|
elbasvir/ grazoprevir (Zepatier®) | 50 mg/100 mg tablet |
Chronic HCV treatment:
|
16 weeks with ribavirin | 50 mg elbasvir and 100 mg grazoprevir once daily |
|
12 weeks | |||
|
12 weeks | |||
|
12 weeks | |||
glecaprevir/pibrentasvir (Mavyret®) | 100 mg/40 mg tablets |
Chronic HCV treatment:
|
8† weeks | 300 mg glecaprevir and 120 mg pibrentasvir once daily |
ledipasvir/ sofosbuvir (Harvoni®, generics) | 90 mg/400 mg tablet |
Chronic HCV treatment:
|
8* weeks or 12 weeks | 90 mg ledipasvir and 400 mg sofosbuvir once daily |
|
12 weeks | |||
|
12 weeks plus ribavirin | |||
|
12 weeks plus ribavirin | |||
genotype 4
|
12 weeks plus ribavirin | |||
|
12 weeks | |||
sofosbuvir/ velpatasvir (Epclusa®, generics) | 400 mg/100 mg tablets |
Chronic HCV treatment:
|
12 weeks | 400 mg sofosbuvir and 100 mg velpatasvir once daily |
|
12 weeks plus ribavirin | |||
sofosbuvir (Sovaldi®) | 400 mg tablet |
Chronic HCV treatment:
|
12 weeks plus ribavirin and peginterferon | 400 mg once daily |
|
12 weeks plus ribavirin | |||
|
24 weeks plus ribavirin |
Legend:
- HCV = hepatitis C virus;
- NS5A inhibitors = Nonstructural protein 5A (NS5A) inhibitors
- NS3/4A protease inhibitors = Nonstructural protein 3/4A protease inhibitors
- † = For HIV/HCV-coinfected patients, a treatment duration of 12 weeks is recommended with compensated cirrhosis (Child-Pugh A) for genotypes 1-4 and genotypes 5 and 6 regardless of liver status
- * = 8 weeks of treatment can be considered in treatment naïve genotype 1 patients without cirrhosis who have pretreatment HCV RNA less than 6 million IU/mL
Drug Name | Dosage Form/Strength | Treatment Indication | Duration and Coadministration | Maximum Recommended Dosage |
---|---|---|---|---|
elbasvir/grazoprevir (Zepatier®) | 50 mg/100 mg tablet |
Chronic HCV treatment:
|
12 weeks | 50 mg elbasvir and 100 mg grazoprevir once daily |
|
16 weeks plus ribavirin | |||
|
12 weeks plus ribavirin | |||
genotype 1b:
|
12 weeks | |||
|
12 weeks plus ribavirin | |||
|
16 weeks plus ribavirin | |||
glecaprevir/ pibrentasvir (Mavyret®) | 100 mg/40 mg tablets |
Chronic HCV treatment:
|
16 weeks | 300 mg glecaprevir and 120 mg pibrentasvir once daily |
|
12 weeks | |||
|
8 weeks | |||
|
12 weeks | |||
|
16 weeks | |||
ledipasvir/sofosbuvir (Harvoni®, generics) | 90 mg/400 mg tablet |
Chronic HCV treatment:
|
12 weeks | 90 mg ledipasvir and 400 mg sofosbuvir once daily |
|
24 weeks or 12 weeks in combination with ribavirin† | |||
|
12 weeks plus ribavirin | |||
|
12 weeks plus ribavirin | |||
|
12 weeks plus ribavirin | |||
|
12 weeks | |||
sofosbuvir/velpatasvir (Epclusa®, generics) | 400 mg/100 mg tablets |
Chronic HCV treatment:
|
12 weeks | 400 mg sofosbuvir and 100 mg velpatasvir once daily |
|
12 weeks plus ribavirin | |||
sofosbuvir (Sovaldi®) | 400 mg tablet |
Chronic HCV treatment:
|
12 weeks plus ribavirin | 400 mg once daily |
|
24 weeks plus ribavirin | |||
sofosbuvir, velpatasvir, and voxilaprevir (Vosevi®) | 400 mg/100 mg/100 mg |
Chronic HCV treatment:
|
12 weeks | 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir once daily |
|
12 weeks |
1.2. Pediatrics
Safety and efficacy of DAAs for use in children younger than 18 years of age has been established with sofosbuvir (Sovaldi®), sofosbuvir/velpatasvir (Epclusa®), glecaprevir/pibrentasvir (Mavyret®), elbasvir/grazoprevir (Zepatier®), and ledipasvir/ sofosbuvir (Harvoni®)2-8, 10-11. Safety and effectiveness of sofosbuvir/velpatasvir/voxilaprevir (Vosevi®) has not been established in pediatric patients less than 18 years of age9. Recommended DAA dosages in pediatric patients are summarized in Table 3.
Drug Name | Dosage Form/Strength | Treatment Indication | Duration and Coadministration | Maximum Recommended Dosage |
---|---|---|---|---|
elbasvir/grazoprevir (Zepatier®) | 50 mg/100 mg tablet |
Chronic HCV treatment in pediatric patients 12 years of age and older weighing at least 30kg with or without mild hepatic impairment (Child-Pugh A):
|
12 weeks | Patients 12-17 years of age: 50 mg elbasvir and 100 mg grazoprevir tablet once daily |
genotype 1a: treatment naïve or peginterferon and ribavirin experienced with baseline NS5A polymorphisms∆ | 16 weeks plus ribavirin* | |||
genotype 1b: treatment naïve or peginterferon and ribavirin experienced | 12 weeks | |||
genotypes 1a£ or 1b: Peginterferon, ribavirin, and NS3/4A protease inhibitor experienced | 12 weeks plus ribavirin* | |||
genotype 4: treatment naïve | 12 weeks | |||
genotype 4: treatment naïve or peginterferon and ribavirin experienced | 16 weeks plus ribavirin* | |||
glecaprevir/pibrentasvir (Mavyret®) |
100 mg/40 mg tablets 50 mg/20 mg oral pellet packets |
Chronic HCV treatment in pediatric patients 3 years of age and older:
|
8 weeks |
|
genotype 1 previously treated with an NS5A inhibitor (ledipasvir and sofosbuvir or daclatasvir with pegylated or nonpegylated interferon plus ribavirin) without prior NS3/4A treatment without cirrhosis or with compensated cirrhosis (Child-Pugh A) | 16 weeks | |||
genotype 1 liver or kidney transplant recipients previously treated with an NS5A inhibitor without prior NS3/4A treatment | 16 weeks | |||
genotype 1 previously treated with an NS3/4A protease inhibitor (containing simeprivir, and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated or nonpegylated interferon and ribavirin) without previous NS5A inhibitor treatment | 12 weeks | |||
genotypes 1, 2, 4, 5, or 6 previously treated with peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor without cirrhosis | 8 weeks | |||
genotypes 1, 2, 4, 5, or 6 previously treated with peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor with compensated cirrhosis (Child-Pugh A) | 12 weeks | |||
genotype 3 previously treated with peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor | 16 weeks | |||
genotype 3 liver or kidney transplant recipients previously treated with peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor | 16 weeks | |||
Liver or kidney transplant recipients | 12 weeks | |||
ledipasvir/sofosbuvir (Harvoni®, generics) |
33.75 mg/150 mg oral pellet packets 45 mg/200 mg oral pellet packets 45 mg/200 mg tablet 90 mg/400 mg tablet |
Chronic HCV treatment in pediatric patients 3 years of age and older:
|
8¥ or 12 weeks |
|
treatment experienced† without cirrhosis | 12 weeks | |||
treatment experienced† with compensated cirrhosis (Child-Pugh A) | 24 weeks** | |||
treatment naïve and treatment experienced† with decompensated cirrhosis (Child-Pugh B or C) | 12 weeks plus ribavirin | |||
genotype 1 or 4 treatment naïve and treatment experienced† liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A) | 12 weeks plus ribavirin | |||
genotype 4,5, or 6 treatment naïve or experienced† patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) | 12 weeks | |||
sofosbuvir/velpatasvir (Epclusa®, generics) |
150 mg/37.5 mg oral pellet packets 200 mg/50 mg oral pellet packets 200 mg/50 mg tablets 400 mg/100 mg tablets |
Chronic HCV treatment pediatric patients 3 years of age and older:
|
12 weeks |
Weight based dosing for patients 3-17 years of age:
|
genotype 1, 2, 3, 4, 5, or 6 that are treatment naïve or experienced†† with decompensated cirrhosis (Child-Pugh B and C) | 12 weeks plus ribavirin | |||
sofosbuvir (Sovaldi ®) |
150 mg oral pellet packet 200 mg oral pellet packet 200 mg tablet 400 mg tablet |
Chronic HCV genotype 2 or 3 treatment for pediatric patients 3 years of age and older without cirrhosis or with compensated cirrhosis (Child-Pugh A)
|
12 weeks plus ribavirin* |
Weight based dosing for patients 3-17 years of age:
|
genotype 3 for treatment naïve or experienced# patients | 24 weeks plus ribavirin* |