Daclatasvir is the first HCV antiviral that targets non-structural protein 5A (NS5A) to prevent viral replication and virion assembly.
Must be used with other antivirals
Daklinza is licensed for use with sofosbuvir (Sovaldi) for 12 weeks in patients with genotype 1 or 4 infection without cirrhosis or for 24 weeks in those with compensated cirrhosis. Patients with genotype 3 infection (previously treated, and/or with compensated cirrhosis) should receive daclatasvir and sofosbuvir plus ribavirin for 24 weeks.
Daklinza can also be used to treat genotype 4 infection in combination with peginterferon alfa and ribavirin. All three drugs are given together for 24 weeks, with a further 24 weeks of interferon alfa and ribavirin if necessary.
The standard dose of daclatasvir is 60mg once daily with or without food. This should be reduced to 30mg once daily if the patient is taking a strong CYP3A4 inhibitor, such as HIV protease inhibitors, azole antifungals, macrolides or calcium channel blockers. The dose should be increased to 90mg once daily if the patient is taking a moderate inducer of CYP3A4, such as efavirenz. Use is contraindicated in patients receiving strong CYP3A4 inducers, such as phenytoin, carbamazepine, rifampicin, systemic dexamethasone and St John's wort.
Efficacious and well-tolerated
High rates of sustained virological response (SVR) have been observed in trials of daclatasvir. In an open-label study (n=211), most patients who received treatment with daclatasvir plus sofosbuvir (with or without ribavirin) had a sustained virologic response at 12 weeks regardless of viral subtype or failure of prior treatment with protease inhibitors, including 98% of patients with genotype 1 infection and 91% of patients infected with genotype 2 or 3.
The most frequently reported adverse events reported with daclatasvir were fatigue, headache and nausea. The rate of discontinuation due to adverse events in the sofosbuvir combination study was low (<1%).