Daclinza, pills 60mg 28pcs

Composition

Film-coated tablets of light green color, biconvex, pentagonal, with the inscription “BMS” on one side and “215” on the other.

1 tab. daclatasvir dihydrochloride 66 mg, which corresponds to the content of daclatasvir 60 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, Opadry® green – 15 mg (hypromellose – 8.9625 mg, titanium dioxide – 4.2825 mg, macrogol-400 – 1.35 mg, aluminum lacquer based on Indigo Carmine (FD & C Blue #2) – 0.255 mg, iron oxide yellow – 0.15 mg).

14 pcs. – blisters (2) – cardboard packs.

Pharmacological action

Daclatasvir (Daklinza) is an antiviral drug in combination with other medications for the treatment of chronic hepatitis C in adults. Daclinza medicine contains the Active ingredient Daclatasvir

Indications

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.

Contraindications

-the drug should not be used as monotherapy;

– hypersensitivity to daclatasvir and/or any of the auxiliary components of the drug;

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

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

– antibacterial agents (rifampicin, rifabutin, rifapentim);

– systemic corticosteroids (dexamethasone);

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

— concurrent use of moderate inducers of CYP3A4 is contraindicated in the use of schemes, including asunaprevir (see instructions to the drug Sunware);

— in the presence of contraindications to the use of drugs combined circuit (asunaprevir and/or peginterferon Alfa+ribavirin) – see the instructions for use of appropriate medications;

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

— pregnancy and lactation period;

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

With caution

Since the drug is used as a combination regimen, combination therapy should be used with caution in the conditions described in the instructions for use of each drug included 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, as well as in patients after liver transplantation.

Concomitant use of Daclinza with other medications may lead to changes in the concentration of both daclatasvir and the active substances of other medications (see the sections “Contraindications” and “Interaction with other medications”).

Side effects

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

The safety of daclatasvir was evaluated in 5 clinical trials in patients with chronic hepatitis C who received 60 mg of Daclinza 1 time / day in combination with asunaprevir and/or peginterferon alfa and ribavirin. Data on the safety of use are presented below for treatment regimens.

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 (frequency of 10% and higher) NLRs observed in clinical trials using the Daclatasvir+therapy regimen Asunaprevir, there was headache (15%) and increased fatigue (12%). Most NLRs were mild to moderate in severity. 6% of patients experienced serious adverse events (SNA),3% of patients stopped treatment due to the occurrence of NLR. At the same time, the most common adverse events (AES) leading to discontinuation of treatment were increased ALT and ACT activity. In a clinical trial of Daclatasvir+therapy Asunaprevir during the first 12 weeks of treatment, the frequency of reported NLRs was similar between patients treated with placebo and those treated with the indicated therapy.

NLRs that occurred in ≥5% of patients with chronic hepatitis C when using the Daclatasvir + combination Asunaprevir, presented below. The frequency of NLR occurrence is given according to the scale: very common (≥1/10), common (≥1/100 and

Table 2.

Adverse reactionsiaNervous system disordersVery frequent headache (15%)Gastrointestinaldisorders hemodiarrhoea (9%), nausea (8%)Common disordersVery frequent fatigue (12%)Laboratory and instrumental dataFrequently increased ALT (7%), increased ACT (5%)

a-side effects, the connection of which with the use of the drug is at least possible. Combined data from several studies.

Adverse reactions that occur in less than 5% of patients with chronic hepatitis C when using the Daclatasvir + combination Asunaprevir: skin rash, pruritus, alopecia; zosinophilia, thrombocytopenia, anemia; fever, malaise, chills; insomnia; decreased appetite, abdominal discomfort, constipation, upper abdominal pain, stomatitis, bloating, vomiting; increased blood pressure; joint pain, muscle rigidity; nasopharyngitis, oropharyngeal pain; increased gamma globulintransferase activity ALP, lipases, and hypoalbuminemia.

Daclatasvir in combination with asunaprevir, peginterferon alfa and ribavirin

The safety of daclatasvir in combination with asunaprevir, peginterferon alfa, and ribavirin was evaluated in a HALLMARK QUAD clinical trial with an average treatment duration of 24 weeks. The most common NLRs (frequency of 15% and higher) observed in clinical trials when using the Daclatasvir + therapy regimen. Asunaprevir+Peginterferon alpha+Ribavirin were: increased fatigue (39%), headache (28%), pruritus (25%), asthenia (23%), flu-like condition (22%), insomnia (21%), anemia (19%), rash (18%), alopecia (16%), irritability (16%) and nausea (15%). Additional side effects that occurred in patients with chronic hepatitis C when using the Daclatasvir therapy regimen+Asunaprevir+Peginterferon alpha+Ribavirin had: dry skin (15%), decreased appetite (12%), muscle pain (14%), fever (15%), cough (13%), shortness of breath (11%), neutropenia (14%), lymphopenia (1%), diarrhea (14%), joint pain (9%). Most NLRs were mild to moderate in severity. 6% of patients reported SES. 5% of patients discontinued treatment for AES, with the most common AES. leading to discontinuation of treatment were rash, malaise, dizziness, and neutropenia.

In a clinical trial of Daclatasvir + therapy Asunaprevir+Peginterferon alpha+Ribavirin the frequency of reported adverse reactions was similar between patients treated with placebo and those treated with the indicated therapy, with the exception of 2 NLRs-asthenia and flu-like condition. These NLRs were the only ones that occurred with a frequency at least 5% higher than among patients receiving placebo.

Results of laboratory tests

Pathological deviations of laboratory parameters from the norm of 3-4 degrees observed among patients with chronic hepatitis C who received combined treatment with Daclinza are presented in Table 3.

Table 3. Pathological deviations of laboratory parameters from the norm of 3-4 degrees observed in clinical studies of therapy with Daclinza in combination therapy

For the parameterDaclatasvir in combination with asunaprevir n=918Daclatasvir in combination with asunaprevir, peginterferon alfa, ribavirin n=398Increased ALT activity (>5.1×UGNb)4%3%Increased AST activity (>5.1×ULN)3%3%Increased total bilirubin concentration (>2.6 ULN)1%1%

a-laboratory results were classified according to the DAIDS system for classifying the severity of adverse events in adults and children, version 1.0 b-upper limit of normal

If any of the NLRs listed in the instructions get worse or you notice any other side effects that are not listed in the instructions, tell your doctor.

How to take it, course of administration and dosage

Recommended dosage regimen

The recommended dose of Daclinza is 60 mg 1 time / day, regardless of the dose of food. The drug should be used in combination with other medications (see Table 1). Recommendations on the dosage of other drugs of the scheme are given in the relevant 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 treatment regimens of Daclinza when used at a dose of 60 mg 1 time / day as part of combination therapy

HCV genotypeTreatmentDurationGenotype 1bdaclatacvir+asunaprevir 24 weeks Genotype 1 daclatasvir+asunaprevir+peginterferon alfa and ribavirin 24 weeks

Changing the dose and suspending therapy

After starting therapy, changing the dose of Daclinza is not recommended. To change the dose of other medications in the regimen, you should read the relevant instructions for medical use. Discontinuation of treatment should be avoided; however, if discontinuation of treatment with any of the regimens is necessary due to adverse reactions, Daclinza should not be used as monotherapy.

During treatment, it is necessary to monitor the viral load (the amount of HCV RNA in the patient’s blood). Patients with an inadequate virological response during treatment are less likely to achieve SVR, and this group is also more likely to develop resistance. Discontinuation of treatment is recommended in patients with a virological breakthrough – an increase in HCV RNA levels by more than 1 log10 from the previous level.

Skipping a dose

If you miss the next dose of Daclinza for up to 20 hours, the patient should take the drug as soon as possible and continue to adhere to the original treatment regimen. If more than 20 hours have passed from the planned time of taking the drug when skipping a dose, the patient should skip taking this dose, and the next dose of the drug should be taken in accordance with the initial therapy scheme.

Patients with renal insufficiency

No dose adjustment is required in patients with any degree of renal insufficiency.

Patients with hepatic insufficiency

No dose adjustment is required in patients with mild hepatic insufficiency (Child-Pugh class A). In studies with mild (Child-Pugh class A), moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic insufficiency, no significant changes in the pharmacokinetics of the drug were detected. The efficacy and safety of its use in decompensated hepatic insufficiency has not been established.

Concomitant therapy

Strong inhibitors of cytochrome P450 isoenzyme 3A4 (CYP3A4)

The dose of Daclinza should be reduced to 30 mg 1 time / day in the case of concomitant use with powerful inhibitors of the CYP3A4 isoenzyme (use a 30 mg tablet; do not break the 60 mg tablet) (see the section “Interaction with other drugs and other forms of interaction”). Concomitant use of potent and moderate inhibitors of the CYP3A4 isoenzyme is contraindicated in the use of regimens that include Sunvepra.

Moderate inducers of the CYP3A4 isoenzyme

The dose of Daclinza should be increased to 90 mg 1 time / day (3 tablets 30 mg or 1 tablet 60 mg and 1 tablet 30 mg) with the simultaneous use of moderate inducers of the CYP3A4 isoenzyme (see the section “Interaction with other drugs and other forms of interaction”). Concomitant use of moderate inducers of the CYP3A4 isoenzyme is contraindicated in the use of regimens that include Sunvepra.

Overdose

Symptoms of overdose are not described.

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

Special instructions

Daclinza should not be used as monotherapy.

Of the more than 2,000 patients enrolled in clinical trials of combination therapy with Ducklinza,372 patients had compensated cirrhosis (Child-Pugh class A). There were no differences in the safety and efficacy of therapy among patients with compensated cirrhosis and patients without cirrhosis. The safety and efficacy of Daclinza in patients with decompensated cirrhosis have not been established. No dose adjustment of Ducklinza is required in patients with mild (Child-Pugh class A), moderate (Child-Pugh class B) or severe (Child-Pugh Class C) hepatic impairment.

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

The effect of daclatasvir on the QTc interval was evaluated in a randomized placebo-controlled study in healthy volunteers. Single doses of daclatasvir 60 mg and 180 mg had no clinically significant effect on the Frederick formula-adjusted QTc interval (QTcF). There was no significant association between increased plasma concentrations of daclatasvir and changes in QTc. At the same time, a single dose of daclatasvir 180 mg corresponds to the maximum expected concentration of the drug in blood plasma during clinical use.

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

It is necessary to use adequate methods of contraception within 5 weeks after the end of Daclinza therapy.

Influence on the ability to drive vehicles and mechanisms

Studies of the possible effect of the drug on the ability to drive vehicles and work with mechanisms have not been conducted. If the patient experiences dizziness, impaired attention, blurred vision / decreased visual acuity (AES were observed when using the peginterferon alfa treatment regimen), which may affect the ability to concentrate, he should refrain from driving vehicles and mechanisms.

Active ingredient

Daklatasvir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Indications

Hepatitis