Daclavir

Daclatasvir 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.

Potential for Other Drugs to Affect Daclatasvir: Daclatasvir is a substrate of CYP3A. Therefore, moderate or strong inducers of CYP3A may decrease the plasma levels and therapeutic effect of Daclatasvir. Strong inhibitors of CYP3A (eg, clarithromycin, itraconazole, ketoconazole, ritonavir) may increase the plasma levels of Daclatasvir.

Potential for Daclatasvir to Affect Other Drugs: Daclatasvir 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 Daclatasvir 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.

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.

No data with Daclatasvir in pregnant women are available to inform a drug-associated risk. No information regarding the presence of Daclatasvir in human milk, the effects on the breastfed infant, or the effects on milk production is available.

Risk of adverse reactions or loss of virologic response due to drug interactions. The concomitant use of Daclatasvir and other drugs may result in known or potentially significant drug interactions, some of which may lead to:

• loss of therapeutic effect of Daclatasvir and possible development of resistance
• dosage adjustments of concomitant medications or Daclatasvir
• 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.

Elderly: No dose adjustment of Daclatasvir is required for patients aged ≥65 years.

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.

Hepatic viral infections (Hepatitis C)

There is no known antidote for overdose of Daclatasvir. Treatment of overdose with Daclatasvir should consist of general supportive measures, including monitoring of vital signs and observation of the patient’s clinical status. Because Daclatasvir is highly protein bound (>99%), dialysis is unlikely to significantly reduce plasma concentrations of the drug.

Store at room temperature below 30°C, protect from light. keep out of the reach of children.