Drug Summary
Adverse Effects
Class and Mechanism
Manufacturer for United States
FDA Status
Indications
Genotype 1
- Genotype 1, without cirrhosis: daclatasvir plus sofosbuvir for 12 weeks
- Genotype 1, compensated (Child-Pugh A) cirrhosis*: daclatasvir plus sofosbuvir for 12 weeks
- Genotype 1, decompensated (Child-Pugh B or C) cirrhosis*^: daclatasvir plus sofosbuvir plus ribavirin for 12 weeks
- Genotype 1, post-transplant: daclatasvir plus sofosbuvir plus ribavirin for 12 weeks
*For patients with genotype 1a and cirrhosis, consider screening for the presence of baseline NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93 prior to initiating treatment.
^For HCV genotype 1 patients with Child-Pugh C cirrhosis, the optimal duration of therapy with daclatasvir plus sofosbuvir plus ribavirin has not been established
Genotype 3
- Genotype 3, without cirrhosis: daclatasvir plus sofosbuvir for 12 weeks
- Genotype 3, compensated (Child-Pugh A) or decompensated (Child-Pugh B or C) cirrhosis: daclatasvir plus sofosbuvir plus ribavirin for 12 weeks
- Genotype 3, post-transplant: daclatasvir plus sofosbuvir plus ribavirin for 12 weeks
#For HCV genotype 3 patients with cirrhosis the optimal duration of therapy with daclatasvir plus sofosbuvir, with or without ribavirin, has not been established.
NOTE: For the use of dasabuvir and sofosbuvir in genotype 3 patients with cirrhosis, the AASLD/IDSA guidance recommends 24 weeks of therapy, with or without ribavirin.
Contraindications
Dosing
Dose Modifications of Daclatasvir with CYP3 Inhibitors and Inducers
- With Strong CYP3A Inhibitor and Certain HIV Antiviral Agents: The daclastasvir levels are expected to increase and thus the daclatasvir dose should be reduced to 30 mg once daily.
- With Moderate CYP3A Inducers and Nevirapine: The daclatasvir levels are expected to decrease and the daclatasvir dose should be increased to 90 mg once daily.
- With Strong CYP3A Inducers: Daclatasvir is contraindicated.
- Patients with Renal Impairment: The dose of daclatasvir does not need to be adjusted in patients with any degree of renal impairment. In addition, because daclatasvir is highly protein bound, it is unlikely to be removed by dialysis.
- Patients with Hepatic Impairment: No dose adjustment is recommended for hepatic impairment, including patients with mild (Child-Pugh A), moderate (Child-Pugh B), or severe (Child-Pugh C) hepatic impairment.
Recommended Ribavirin Dosing
- When ribavirin is used in patients with HCV genotype 1 or 3 and either Child-Pugh B or C cirrhosis or post-transplantation patients, the recommended initial dose of ribavirin is 600 mg once daily, increasing up to 1000 mg daily as tolerated. In this scenario, the ribavirin starting dose and on-treatment dose can be decreased based on hemoglobin and creatinine clearance.
- When ribavirin is used in combination with daclatasvir and sofosbuvir in patients with HCV genotype 3 and compensated cirrhosis (Child-Pugh A), the recommended ribavirin dose is weight based (1000 mg for patients weighing less than 75 kg and 1200 mg for those weighing at least 75 kg) and is administered in two divided doses.