Dakovir-C60 mg

Dakovir-C 60 mg is indicated in combination with Sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection in adults.

Hepatic viral infections (Hepatitis C)

Dakovir-C 60 mg stops HCV viral RNA replication and protein translation by directly inhibiting HCV protein NS5A. NS5A is critical for HCV viral transcription and translation.

The recommended dose of Dakovir-C 60 mg is 60 mg once daily, to be taken orally with or without meals. Dakovir-C 60 mg must be administered in combination with other medicinal products.HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C without cirrhosis, including treatment-naïve patients and patients who failed on a treatment based on Peginterferon alfa & Ribavirin All genotypes: Dakovir-C 60 mg + Sofosbuvir for 12 weeks HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C with compensated (Child-Pugh A) cirrhosis, including treatment-naïve patients and patients who failed on a treatment based on Peginterferon alfa & Ribavirin Genotype 1,4,5,6: Dakovir-C 60 mg + Sofosbuvir for 24 weeks or Dakovir-C 60 mg + Sofosbuvir + Ribavirin for 12 weeks Genotype 2: Dakovir-C 60 mg + Sofosbuvir for 12 weeks Genotype 3: Dakovir-C 60 mg + Sofosbuvir + Ribavirin for 24 week The dose of Ribavirin, when combined with Dakovir-C 60 mg, is weight-based (1000 or 1200 mg in patients <75 kg or ≥75 kg, respectively).

Recommended Dosage: The recommended dose of Dakovir-C 60 mg is 60 mg once daily, to be taken orally with or without meals.Dakovir-C 60 mg 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 Dakovir-C 60 mg. Recommended regimens and treatment duration are provided in table below:For the regimen of Dakovir-C 60 mg+Sofosbuvir, data for 12-week treatment duration are available only for treatment-naïve patients with genotype 1 infection. For Dakovir-C 60 mg+Sofosbuvir with or without Ribavirin, data are available for patients with advanced liver disease (≥F3) without cirrhosis. The recommended use of Dakovir-C 60 mg+Sofosbuvir in genotype 4 is based on extrapolation from genotype 1. For the regimen of Dakovir-C 60 mg+Peginterferon alfa + Ribavirin, data are available for treatment-naïve patients. The dose of Ribavirin, when combined with Dakovir-C 60 mg, 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 Dakovir-C 60 mg to manage adverse reactions is not recommended. If treatment interruption of components in the regimen is necessary because of adverse reactions, Dakovir-C 60 mg must not be given as monotherapy. There are no virologic treatment stopping rules that apply to the combination of Dakovir-C 60 mg with Sofosbuvir. Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with Dakovir-C 60 mg, Peginterferon alfa and Ribavirin. Dose recommendation for concomitant medicines: Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4): The dose of Dakovir-C 60 mg should be reduced to 30 mg once daily when coadministered with strong inhibitors of CYP3A4. Moderate inducers of CYP3A4: The dose of Dakovir-C 60 mg 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 Dakovir-C 60 mg, 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 Other Drugs to Affect Dakovir-C 60 mg: Dakovir-C 60 mg is a substrate of CYP3A. Therefore, moderate or strong inducers of CYP3A may decrease the plasma levels and therapeutic effect of Dakovir-C 60 mg. Strong inhibitors of CYP3A (eg, clarithromycin, itraconazole, ketoconazole, ritonavir) may increase the plasma levels of Dakovir-C 60 mg. Potential for Dakovir-C 60 mg to Affect Other Drugs: Dakovir-C 60 mg 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 Dakovir-C 60 mg 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.

Dakovir-C 60 mg is contraindicated in combination with drugs that strongly induce CYP3A and, thus, may lead to lower exposure and loss of efficacy of Dakovir-C 60 mg. Contraindicated drugs include, but are not limited to, Anticonvulsants (phenytoin, carbamazepine), Antimycobacterial agents (rifampin), Herbal Products st.Jhon’s wort (Hypericum perforatum).

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.

Dakovir-C 60 mg 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 Dakovir-C 60 mg therapy. It is not known whether Dakovir-C 60 mg is excreted in human milk.

Risk of adverse reactions or loss of virologic response due to drug interactions. The concomitant use of Dakovir-C 60 mg and other drugs may result in known or potentially significant drug interactions, some of which may lead to: loss of therapeutic effect of Dakovir-C 60 mg and possible development of resistance dosage adjustments of concomitant medications or Dakovir-C 60 mg possible clinically significant adverse reactions from greater exposures of concomitant drugs or Dakovir-C 60 mg 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 Dakovir-C 60 mg. Patients who are taking Sofosbuvir in combination with Dakovir-C 60 mg who need to start Amiodarone therapy due to no other alternative treatment options should undergo cardiac monitoring.

There is no known antidote for overdose of Dakovir-C 60 mg. Treatment of overdose with Dakovir-C 60 mg should consist of general supportive measures, including monitoring of vital signs and observation of the patient’s clinical status. Because Dakovir-C 60 mg 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.

Hepatic viral infections (Hepatitis C)

Dakovir-C 60 mg is a direct acting antiviral agent (DAA) against the Hepatitis C Virus (HCV). Dakovir-C 60 mg is an inhibitor of NS5A, a nonstructural protein encoded by HCV. Dakovir-C 60 mg binds to the N-terminus of NS5A and inhibits both viral RNA replication and virion assembly. Characterization of Dakovir-C 60 mg-resistant viruses, biochemical studies, and computer modeling data indicate that Dakovir-C 60 mg interacts with the N-terminus within Domain 1 of the protein, which may cause structural distortions that interfere with NS5A functions.

No data with Dakovir-C 60 mg in pregnant women are available to inform a drug-associated risk. No information regarding the presence of Dakovir-C 60 mg in human milk, the effects on the breastfed infant, or the effects on milk production is available.

Elderly: No dose adjustment of Dakovir-C 60 mg is required for patients aged ≥65 years.Renal impairment: No dose adjustment of Dakovir-C 60 mg is required for patients with any degree of renal impairment.Hepatic impairment: No dose adjustment of Dakovir-C 60 mg 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 Dakovir-C 60 mg in children and adolescents aged below 18 years have not yet been established. No data are available.