Dosage & Administration
Daclavir must be administered in combination with other medicinal products. The Summary of Product Characteristics for the other medicinal products in the regimen should also be consulted before initiation of therapy with Daclavir. Recommended regimens and treatment duration are provided in table below:
For the regimen of Daclatasvir+Sofosbuvir, data for 12-week treatment duration are available only for treatment-naïve patients with genotype 1 infection. For Daclatasvir+Sofosbuvir with or without Ribavirin, data are available for patients with advanced liver disease (≥F3) without cirrhosis. The recommended use of Daclatasvir+Sofosbuvir in genotype 4 is based on extrapolation from genotype 1. For the regimen of Daclatasvir+Peginterferon alfa + Ribavirin, data are available for treatment-naïve patients.
- The dose of Ribavirin, when combined with Daclatasvir, is weight-based (1,000 or 1,200 mg in patients <75 kg or ≥75 kg, respectively).
- Dose modification, interruption and discontinuation: Dose modification of Daclavir to manage adverse reactions is not recommended. If treatment interruption of components in the regimen is necessary because of adverse reactions, Daclavir must not be given as monotherapy.
- There are no virologic treatment stopping rules that apply to the combination of Daclavir with Sofosbuvir.
- Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with Daclavir, Peginterferon alfa and Ribavirin.
Dose recommendation for concomitant medicines:
- Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4): The dose of Daclatasvir should be reduced to 30 mg once daily when coadministered with strong inhibitors of CYP3A4.
- Moderate inducers of CYP3A4: The dose of Daclatasvir should be increased to 90 mg once daily when coadministered with moderate inducers of CYP3A4.
- Missed doses: Patients should be instructed that, if they miss a dose of Daclatasvir, the dose should be taken as soon as possible if remembered within 20 hours of the scheduled dose time. However, if the missed dose is remembered more than 20 hours after the scheduled dose, the dose should be skipped and the next dose taken at the appropriate time.
Potential for Daclatasvir to Affect Other Drugs: Daclavir is an inhibitor of P-glycoprotein transporter (P-gp), organic anion transporting polypeptide (OATP) 1B1 and 1B3, and breast cancer resistance protein (BCRP). Administration of Daclavir may increase systemic exposure to medicinal products that are substrates of P-gp, OATP 1B1 or 1B3, or BCRP, which could increase or prolong their therapeutic effect or adverse reaction.
Pregnancy & Lactation
Precautions & Warnings
- loss of therapeutic effect of Daclavir and possible development of resistance
- dosage adjustments of concomitant medications or Daclavir
- possible clinically significant adverse reactions from greater exposures of concomitant drugs or Daclatasvir
Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone and patients counseling: Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when Amiodarone is coadministered with Sofosbuvir in combination with another HCV direct-acting antiviral, including Daclatasvir. Patients who are taking Sofosbuvir in combination with Daclatasvir who need to start Amiodarone therapy due to no other alternative treatment options should undergo cardiac monitoring.
Use in Special Populations
Renal impairment: No dose adjustment of Daclatasvir is required for patients with any degree of renal impairment.
Hepatic impairment: No dose adjustment of Daclatasvir is required for patients with mild (Child-Pugh A, score 5-6), moderate (Child-Pugh B, score 7-9) or severe (Child-Pugh C, score ≥10) hepatic impairment.
Paediatric population: The safety and efficacy of Daclatasvir in children and adolescents aged below 18 years have not yet been established. No data are available.