- ACRONYMS AND DEFINITIONS
- DRUGS IN CLASS
- Hepatitis C treatment
- MECHANISM OF ACTION
- Daclatasvir is an inhibitor of the HCV NS5A protein which is essential for viral replication and virion assembly
- FDA-APPROVED INDICATION
- Treatment of HCV genotype 1
- No cirrhosis and Child-Pugh A: in combination with sofosbuvir
- Child-Pugh B/C and post-liver transplant: in combination with sofosbuvir and ribavirin
- Treatment of HCV genotype 3
- No cirrhosis in combination with sofosbuvir
- Child-Pugh A, B, C and post-liver transplant: in combination with sofosbuvir and ribavirin
|HCV cure rates for daclatasvir + sofosbuvir ± ribavirin|
|GT||No cirrhosis or CP A||CP B/C|
|1||> 90%||B > 90%
C ∼ 50%
|3||> 90%||∼ 60%|
- NS5A POLYMORPHISM
- Certain strands of the hepatitis C virus have different amino acid sequences (polymorphisms) in their NS5A protein. These polymorphisms can confer resistance to medications.
- The effectiveness of daclatasvir was reduced in cirrhotic patients with HCV genotype 1a NS5A polymorphisms at M28, Q30, L31, and Y93, and in patients with HCV genotype 3 NS5A polymorphisms at Y93H
- The manufacturer of daclatasvir recommends that providers consider testing for the presence of NS5A polymorphisms at amino acid positions M28, Q30, L31, and Y93 in patients with cirrhosis who are infected with HCV genotype 1a
- The manufacturer makes no recommendation on adjusting therapy based on results
|Patient population||SVR 12
|76% (13/17)||95% (142/149)|
|100% (11/11)||99% (100/101)|
|33% (2/6)||88% (42/48)|
|54% (7/13)||92% (149/162)|
|67% (6/9)||98% (125/128)|
|25% (1/4)||71% (24/34)|
- SIDE EFFECTS
- Daclatasvir was evaluated in the ALLY-3 trial. The ALLY-3 trial was an open-label trial that had no control group.
- Since there was no placebo group, strength of association is unknown
- Only side effects that occurred at an incidence of ≥ 5% and were at least partially thought to be related to study treatment are listed below
- Lipase elevations
- In the ALLY-3 trial, transient lipase elevations > 3 X upper limit of normal were observed in 2% of patients 
- Daclatasvir is contraindicated with CYP3A4 strong inducers including, but not limited to, phenytoin, carbamazepine, rifampin, and St. John's wort
- Kidney disease
- No dose adjustment is necessary in mild, moderate, or severe kidney disease 
- Liver disease
- No dose adjustment is necessary in patients with mild, moderate, or severe liver disease (Child-Pugh A,B,C)
- Safety has not been established in decompensated cirrhosis 
- Hepatitis B coinfection
- In October 2016, the FDA placed a boxed warning on all new hepatitis C drugs about the possible reactivation of hepatitis B infection in coinfected patients who are taking direct-acting antiviral hepatitis C drugs
- At the time of the warning, the FDA had identified 24 cases of hepatitis B reactivation in patients taking these drugs. Reactivation occurred in patients who were HBsAg positive and in those who were HBsAg negative and anti-HBc positive (see hepatitis B serology for more).
- The FDA recommends that providers check all patients for hepatitis B coinfection (HBsAg and anti-HBc) before starting therapy and that they monitor patients for reactivation during and after therapy
- See AASLD guidelines for HBV coinfected patients for more
- MONITORING THERAPY
- DRUG INTERACTIONS
- NOTE: The drug interactions presented here are NOT A COMPREHENSIVE LIST of all known interactions. Other interactions exist. The interactions below are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- HIGH ALERT INTERACTIONS
- Numerous drugs and drug classes
- Daclatasvir is a CYP3A4 sensitive substrate, OATP1B1/B3 inhibitor, and P-glycoprotein substrate and inhibitor. Because of this, daclatasvir has a long list of potential drug interactions.
- See the daclatasvir PI for a review of drug interactions
- METABOLISM AND ELIMINATION
- NOTE: Drugs can be metabolized by more than one enzyme. Drugs may be metabolized by an enzyme and inhibit/induce the enzyme at the same time. Drug transporters (ex. p-glycoprotein) can play a role in drug metabolism. Not all drug interactions are clinically significant. Consult your physician or pharmacist if you are taking medications together and are concerned about a possible interaction.
- Dosage form
- 30 mg tablet
- 60 mg tablet
- The standard dose of daclatasvir is 60 mg once daily
- When taken with certain classes of medications including HIV medications, CYP3A4 strong inhibitors, and CYP3A4 moderate inducers, dose adjustments are recommended. See daclatasvir PI for more.
- May take without regard to food
- Treatment regimens
- HCV Genotype 1✝ (in combination with sofosbuvir ± ribavirin)
- No cirrhosis or Child-Pugh A: Sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily for 12 weeks
- Child-Pugh B, C, or post-liver transplant: Sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily + ribavirin for 12 weeks. Ribavirin should be started at 600 mg once daily and increased to 1000 mg/day as tolerated.
- ✝Genotype 1a with cirrhosis: Consider screening for the presence of NS5A polymorphisms. See polymorphism for more.
- HCV Genotype 3 (in combination with sofosbuvir ± ribavirin)
- No cirrhosis: Sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily for 12 weeks
- Child-Pugh A Sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily + ribavirin for 12 weeks. Ribavirin dosing should be weight-based.
- Child-Pugh B, C, or post-liver transplant Sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily + ribavirin for 12 weeks. Ribavirin should be started at 600 mg once daily and increased to 1000 mg/day as tolerated
- HEPATITIS C TREATMENT RECOMMENDATIONS
- See hepatitis C treatment recommendations for complete treatment guidelines
- LONG TERM SAFETY
- Daclatasvir was FDA-approved in 2015
- There is no long-term safety data for the medication
- GENERIC AVAILABILITY
- Possible generic:
- NOTE: Drug companies typically file multiple patents on their drugs in order to protect them from competition. The patent expiration listed here is the date that the earliest patent on the drug expires (accounting for pediatric exclusivity). Because drug companies use numerous techniques to extend the life of their patents, it does not necessarily mean a generic will become available around this date.
- What is PMID?
- PI = Manufacturer's Package Insert
- 1 - Daclatasvir PI
- 2 - PMID 25614962 ALLY-3 trial