Daclavir is indicated in combination with Sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection in adults.
Daclatasvir is a direct acting antiviral agent (DAA) against the Hepatitis C Virus (HCV). Daclatasvir is an inhibitor of NS5A, a nonstructural protein encoded by HCV. Daclatasvir binds to the N-terminus of NS5A and inhibits both viral RNA replication and virion assembly. Characterization of Daclatasvir-resistant viruses, biochemical studies, and computer modeling data indicate that Daclatasvir interacts with the N-terminus within Domain 1 of the protein, which may cause structural distortions that interfere with NS5A functions.
Recommended Dosage : The recommended dose of Daclatasvir is 60 mg once daily, to be taken orally with or without meals. Daclatasvir 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 Daclatasvir. 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 Daclatasvir to manage adverse reactions is not recommended. If treatment interruption of components in the regimen is necessary because of adverse reactions, Daclatasvir must not be given as monotherapy. There are no virologic treatment stopping rules that apply to the combination of Daclatasvir with Sofosbuvir. Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with Daclatasvir, 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.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
The following serious adverse reactions are described below and elsewhere in the labeling: Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone. One can get any of the following symptoms: Fainting or near-fainting, dizziness or lightheadedness, not feeling well, weakness, tiredness, shortness of breath, chest pain, confusion, memory problems.
Daclatasvir is contraindicated in combination with drugs that strongly induce CYP3A and, thus, may lead to lower exposure and loss of efficacy of Daclatasvir. Contraindicated drugs include, but are not limited to, Anticonvulsants (phenytoin, carbamazepine), Antimycobacterial agents (rifampin), Herbal Products st.Jhon’s wort (Hypericum perforatum).
Potential for Other Drugs to Affect Daclavir : Daclavir is a substrate of CYP3A. Therefore, moderate or strong inducers of CYP3A may decrease the plasma levels and therapeutic effect of Daclavir. Strong inhibitors of CYP3A (eg, clarithromycin, itraconazole, ketoconazole, ritonavir) may increase the plasma levels of Daclavir. Potential for Daclavir 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.
Risk of adverse reactions or loss of virologic response due to drug interactions. The concomitant use of Daclavir and other drugs may result in known or potentially significant drug interactions, some of which may lead to: 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 Daclavir 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 Daclavir. Patients who are taking Sofosbuvir in combination with Daclavir who need to start Amiodarone therapy due to no other alternative treatment options should undergo cardiac monitoring.