Daclatasvir

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. It is used along with other medications for the treatment of chronic hepatitis C virus (HCV) infection. It works by lowering a load of hepatitis C virus in the body and removing the virus from the blood over a period of time.

• Chronic hepatitis C virus (HCV) infection (genotypes 1 and 3)

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.

Daclatasvir binds to the NS5A protein of HCV, inhibiting viral RNA replication and virion assembly, thereby reducing the hepatitis C virus load and eliminating the virus from the blood.

Adult - HCV Genotype 1 (with Sofosbuvir): 60 mg (plus Sofosbuvir 400 mg) orally once daily for 12 weeks.

Adult - HCV Genotype 3 (with Sofosbuvir): 60 mg (plus Sofosbuvir 400 mg) orally once daily for 12 weeks.

Cirrhosis (Child-Pugh B or C) or posttransplant: 60 mg (plus Sofosbuvir 400 mg) + Ribavirin once daily for 12 weeks.

With strong CYP3A4 inhibitors: Reduce dose to 30 mg once daily.

With moderate CYP3A4 inducers: Increase dose to 90 mg once daily.

May be taken with or without food, but it is better to take it at a fixed time. Swallow it as a whole. Do not chew, crush or break it. Take in the dose and duration as advised by your doctor.

If you miss a dose of Daclatasvir, take it as soon as possible if remembered within 20 hours of the scheduled dose time. If the missed dose is remembered more than 20 hours after the scheduled dose, skip the dose and take the next dose at the appropriate time.

Common Side Effects:

• Fatigue
• Headache
• Nausea
• Insomnia
• Anemia
• Dizziness
• Blurred vision

Serious Side Effects:

• Symptomatic bradycardia when coadministered with Sofosbuvir and Amiodarone

• Daclatasvir may have significant drug interactions with other drugs, which may lead to loss of therapeutic effect or development of resistance.
• Risk of symptomatic bradycardia when coadministered with Sofosbuvir and Amiodarone.
• May affect your ability to drive (fatigue, dizziness, blurred vision).
• Monitor liver function and HCV viral load regularly during treatment.
• Do not stop taking Daclatasvir without your doctor's advice.

• Hypersensitivity
• Coadministration with strong CYP3A4 inducers and P-gp (phenytoin, carbamazepine, oxcarbazepine, phenobarb, rifampicin, rifabutin, rifapentine, systemic dexamethasone, St. John's wort)

Strong/Moderate CYP3A4 and P-gp inducers (phenytoin, carbamazepine, rifampicin, dexamethasone, St. John's wort): Decreased plasma levels and therapeutic effect.

Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir): Increased plasma levels.

P-gp, OATP 1B1/1B3, BCRP substrates (dabigatran, digoxin, calcium channel blockers, HMG-CoA reductase inhibitors): May increase systemic exposure.

Boceprevir, telaprevir, atazanavir/ritonavir, efavirenz, clarithromycin, erythromycin, amiodarone: Caution required.

It is not known whether it is safe to consume alcohol with Daclatasvir. Please consult your doctor. Can be taken with or without food.

No data with Daclatasvir in pregnant women are available. Animal studies have shown harmful effects. Your doctor will weigh the benefits and any potential risks. Please consult your doctor.

No information regarding the presence of Daclatasvir in human milk, the effects on the breastfed infant, or the effects on milk production is available. Please consult your doctor.

Safety and efficacy in children and adolescents below 18 years have not yet been established.

No dose adjustment is required for patients aged ≥65 years.

Renal impairment: No dose adjustment is required for patients with any degree of renal impairment.

Hepatic impairment: No dose adjustment is required for patients with mild, moderate or severe hepatic impairment (Child-Pugh A, B, C).

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

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

Daclatasvir