Daclinza, 60 mg 28 pcs.

Daclatasvir (Daklinza) is an antiviral drug in combination with other medicines to treat
chronic hepatitis C in adults.
The drug Daklinza contains the active ingredient Daclatasvir

Indications

The treatment of chronic hepatitis C in patients with compensated liver disease (including cirrhosis) in the following combinations of daclatasvir:

– with asunaprevir for patients with hepatitis virus genotype 1b;

– with asunaprevir, peginterferon alfa, and ribavirin for patients with hepatitis virus genotype 1.

Active ingredient

Composition

Film-coated tablets are light green, biconvex, pentagonal, engraved “BMS” on one side and “215” on the other.

1 tablet daclatasvir dihydrochloride66 mg, which corresponds to the content of daclatasvir60 mg

Auxiliary substances: lactose – 115.5 mg, microcrystalline cellulose – 95.7 mg, croscarmellose sodium – 15 mg, silicon dioxide – 3 mg, magnesium stearate – 4.8 mg, opadray® green – 15 mg (hypromellose – 8.9625 mg, titanium dioxide – 4.2825 mg, macrogol-400 – 1.35 mg, indigo carmine-based aluminum varnish (FD&C Blue #2) – 0.255 mg, iron oxide yellow – 0.15 mg).

14 pcs. – Blisters (2) – cardboard boxes.

How to take, the dosage

Recommended dosing regimen

The recommended dose of Daclinza is 60 mg once daily regardless of meals. The drug should be used in combination with other medicinal agents (see Table 1). Recommendations for doses of other drugs are given in the corresponding instructions for medical use. Therapy is recommended both for patients who have not previously received treatment for chronic hepatitis C and for patients with previous ineffectiveness of therapy.

Table 1. Recommended therapy regimens for Daclinza when used at a dose of 60 mg once daily as part of combination therapy

HCV genotypeTreatmentDurationGenotype 1bdaclitacvir+asunaprevir24 weeksGenotype 1daclitacvir+asunaprevir+peginterferon alfa and ribavirin24 weeks

Dose changesEm>Dose changes and suspension of therapy

No dose changes are recommended for Daclinza once therapy has started. To change the dose of other drugs in the regimen, consult the corresponding instructions for medical use. Interruption of treatment should be avoided; however, if interruption of treatment with any drug in the regimen is necessary due to adverse reactions, Daclinza should not be used as monotherapy.

Viral load (the amount of HCV RNA in the patient’s blood) should be monitored during treatment. Patients with an inadequate virologic response during treatment are unlikely to achieve SVR, and this group is also likely to develop resistance. Discontinuation of treatment is recommended in patients with a virologic breakthrough – an increase in HCV RNA levels of more than 1 log10 from the previous level.

Dose skipping

If the next dose of Daclinsa is missed for up to 20 hours, the patient should take the drug as soon as possible and continue with the original therapy regimen. If the missed dose is more than 20 hours from the planned time of taking the drug, the patient should skip the dose, and the next dose of the drug should be taken according to the original therapy regimen.

Patients with renal impairment

Dose changes in patients with any degree of renal impairment are not required.

Patients with hepatic impairment

Dose changes in patients with mild hepatic impairment (Child-Pugh grade A) are not required. No significant changes in pharmacokinetics of the drug were found in studies with mild (Child-Pugh class A), moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic failure. Efficacy and safety of use in decompensated hepatic insufficiency have not been established.

Companion therapy

.Strong inhibitors of cytochrome P450 isoenzyme 3A4 (CYP3A4)

The dose of Daclinza should be reduced to 30 mg once daily if used concomitantly with potent CYP3A4 isoenzyme inhibitors (use the 30 mg tablet; do not break the 60 mg tablet) (see section “Interaction with other medicinal products and other forms of interaction”). Simultaneous use of potent and moderate CYP3A4 isoenzyme inhibitors is contraindicated in regimens including Sunvepra.

Moderate CYP3A4 isoenzyme inducers

The dose of Daclinza should be increased to 90 mg once daily (3 tablets 30 mg or 1 tablet 60 mg and 1 tablet. 30 mg) when concomitant use of moderate inducers of CYP3A4 isoenzyme (see section “Interaction with other medicinal products and other forms of interaction”). Concomitant use of moderate CYP3A4 isoenzyme inducers is contraindicated in regimens including Sunvepra.

Special Instructions

The drug Daclinza should not be used as monotherapy.

Of more than 2,000 patients enrolled in clinical trials of combination therapy with Daclinza, 372 patients had compensated cirrhosis (Child-Pugh class A). No differences in safety and efficacy of therapy among patients with compensated cirrhosis and patients without cirrhosis were observed. Safety and efficacy of Daclinsa in patients with decompensated cirrhosis have not been established. There is no need to change the dose of Daclinza in patients with mild (Child-Pugh grade A), moderate (Child-Pugh grade B) or severe (Child-Pugh grade C) impaired liver function.

The safety and efficacy of Daclinsa combination therapy in patients with liver transplantation has not been established. There is limited experience with Daclinza after liver transplantation.

The effect of daclatasvir on the QTc interval has been evaluated in a randomized placebo-controlled trial in healthy volunteers. Single doses of daclatasvir 60 mg and 180 mg had no clinically significant effect on the QTc interval adjusted by the Frederick formula (QTcF). There was no significant relationship between elevated plasma concentrations of daclatasvir and changes in QTc. A single dose of daclatasvir 180 mg is consistent with the maximum expected plasma concentrations of the drug in clinical use.

The use of the drug for treatment of chronic hepatitis C in patients with co-infection with hepatitis B virus or human immunodeficiency virus has not been studied. Daclinza contains lactose: in 1 tablet. 60 mg (daily dose) contains 115.50 mg of lactose.

It is necessary to use adequate methods of contraception for 5 weeks after completion of therapy with Daclinza.

Influence on driving and operating machinery

There have been no studies of possible effect of the drug on driving and operating machinery. If a patient experiences dizziness, impaired attention, blurred/reduced visual acuity (NODs have been reported with peginterferon alfa regimen) which may affect the ability to concentrate, the patient should refrain from driving vehicles and operating machinery.

Contraindications

– the drug should not be used as monotherapy;

– hypersensitivity to daclatasvir and/or any of the drug’s excipients;

– in combination with strong CYP3A4 isoenzyme inducers (due to reduced blood concentration of daclatasvir and reduced effectiveness), such as:

– antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, oxcarbazepine);

– antibacterials (rifampicin, rifabutin, rifapentim);

– systemic GCS (dexamethasone);

– herbal remedies (preparations based on St. John’s Wort (Hypericum perforatum)).

– concomitant use of moderate CYP3A4 isoenzyme inducers is contraindicated with regimens that include asunaprevir (see Sunvepra instructions);

– if there are contraindications to the use of drugs in the combination regimen (asunaprevir and/or peginterferon alfa+ribavirin) – see the instructions for use of the respective drugs.

– lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

– pregnancy and lactation;

– age under 18 years (effectiveness and safety have not been studied).

Cautions

Since the drug is used as a combination regimen, combination therapy should be used with caution for the conditions described in the instructions for use of each drug in the regimen (asunaprevir and/or peginterferon alfa and ribavirin).

The safety of combination therapy has not been studied in patients with decompensated liver disease or in patients after liver transplantation.

The co-administration of Daclinsa with other drugs may lead to changes in concentrations of both daclatasvir and the active ingredients of other drugs (see “Contraindications” and “Interaction with other medicinal products”).

Side effects

Daclinza is only used as part of a combination therapy regimen. You should familiarize yourself with the side effects of the drugs included in the treatment regimen before starting therapy. Adverse drug reactions (ADRs) associated with asunaprevir, peginterferon alfa, and ribavirin are described in the medical instructions for use of these drugs.

The safety of daclatasvir was evaluated in 5 clinical trials in patients with chronic hepatitis C receiving 60 mg of daclinza once daily in combination with asunaprevir and/or peginterferon alfa and ribavirin. Safety data are presented below by treatment regimen.

Daclatasvir + Asunaprevir

The safety of daclatasvir in combination with asunaprevir was evaluated in 4 studies with an average duration of therapy of 24 weeks. The most common (incidence of 10% or higher) HRs observed in clinical trials with the daclatasvir+asunaprevir therapy regimen were headache (15%) and increased fatigue (12%). The majority of the NCDs were mild to moderate in severity. 6% of patients experienced serious adverse events (AEs), and 3% of patients discontinued treatment due to the occurrence of AEs. The most common adverse events (AEs) leading to treatment discontinuation were ALT and ACT elevations. In a clinical trial of Daclatasvir+Asunaprevir therapy during the first 12 weeks of treatment, the rate of reported NLDs was similar between patients receiving placebo and those receiving this therapy.

The NLDs that occurred in ≥5% of patients with chronic hepatitis C with the Daclatasvir+Asunaprevir combination are shown below. The incidence of NLDs is given according to a scale: very common (≥1/10), common (≥1/100 and < 1/10).

Table 2.

Background reactionsaNervous system disordersVery commonHeadache (15%)Gastrointestinal disordersFrequentDiarrhea (9%), nausea (8%)General disorders

Overdose

No symptoms of overdose have been described.

In phase I clinical trials, no unanticipated adverse reactions were observed when doses of up to 100 mg for up to 14 days or a single dose of up to 200 mg were used in healthy volunteers. There is no antidote to daclatasvir. Treatment of drug overdose should include general supportive measures, including monitoring of vital signs and observation of the patient’s clinical condition. Due to high plasma protein binding of daclatasvir, dialysis is not recommended in case of overdose.