DEFLAZA

Daclatasvir is indicated in combination with Sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection in adults.

Hepatic viral infections (Hepatitis C)

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.

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. HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C without cirrhosis, including treatment-na?ve patients and patients who failed on a treatment based on Peginterferon alfa & Ribavirin All genotypes: Daclatasvir + Sofosbuvir for 12 weeks HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C with compensated (Child-Pugh A) cirrhosis, including treatment-na?ve patients and patients who failed on a treatment based on Peginterferon alfa & Ribavirin Genotype 1,4,5,6: Daclatasvir + Sofosbuvir for 24 weeks or Daclatasvir + Sofosbuvir + Ribavirin for 12 weeks Genotype 2: Daclatasvir + Sofosbuvir for 12 weeks Genotype 3: Daclatasvir + Sofosbuvir + Ribavirin for 24 week The dose of Ribavirin, when combined with Daclatasvir, is weight-based (1000 or 1200 mg in patients <75 kg or ?75 kg, respectively).

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.

Strong inducers of CYP3A, including phenytoin, carbamazepine, rifampicin, and St. John’s wort Hypersensitivity to the active substance or to any of the excipients. Bradycardia with Sofobuvir and Amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone with Sofosbuvir in combination with Daclatasvir, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with Sofobuvir in combination with Daclatasvir is not recommended. Daclatasvir must not be administered as monotherapy. Daclatasvir must be administered in combination with other medicinal products for the treatment of chronic HCV infection.

Daclatasvir in combination with Sofosbuvir: Fatigue, headache, nausea. Daclatasvir in combination with Peginterferon alfa and Ribavirin: The most frequently reported adverse reactions were fatigue, headache, pruritus, insomnia, influenza-like illness, dry skin, nausea, decreased appetite, alopecia, rash, asthenia, irritability, myalgia, anaemia, pyrexia, cough, dyspnoea, neutropenia, diarrhoea and arthralgia.

Daclatasvir should not be used during pregnancy or in women of childbearing potential not using contraception. Use of highly effective contraception should be continued for 5 weeks after completion of Daclatasvir therapy. It is not known whether daclatasvir is excreted in human milk.

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.

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