Medicinal Products

DAKLINZA 30 mg

Generic drug of the therapeutic class: Gastro-Entero-Hepatology
Active ingredients: Daclatasvir
laboratory: Bristol-Myers Squibb Eeig

Coated tablet
Box of 28 blister packs of 1
All forms

Indication

Daklinza is indicated for use in combination with other medicinal products for the treatment of chronic hepatitis C virus (HCV) infection in adults (see section 4.2 Posology and method of administration, Warnings and precautions for use). use and pharmacodynamic properties ).

For hepatitis C virus (HCV) genotype activity, see sections Warnings and Precautions and Pharmacodynamic Properties .

Dosage DAKLINZA 30 mg Film-coated tablet Box of 28 blister packs of 1

Treatment with Daklinza should be initiated and monitored by a physician experienced in the management of chronic hepatitis C.

Dosage

The recommended dose of Daklinza is 60 mg once daily, taken orally, with or without food.

Daklinza should be given in combination with other medicines. Summaries of Product Characteristics of co-administered drugs should also be consulted prior to initiation of Daklinza therapy.

The co-administered drugs and the recommended duration of treatment are shown in Table 1 below (see also Warnings and Precautions and Pharmacodynamic Properties ):

Table 1: Co-Administered Drugs and Recommended Duration of Treatment for Daklinza Combination Therapy

HCV genotype and patient population *

Treatment

Duration

G enotype 1 or 4 without cirrhosis

Daklinza + sofosbuvir

12 weeks

An extension of the duration of treatment up to 24 weeks should be considered for patients who have been treated with an NS3 / 4A anti-protease (see sections Warnings and Precautions and Pharmacodynamic Properties )

Genotype 1 or 4 with compensated cirrhosis

Daklinza + sofosbuvir

24 weeks

A shorter treatment duration of 12 weeks may be considered in treatment-naive, cirrhotic patients with good-response predictors such as: IL28B CC and / or low viral load at initiation of treatment.

The addition of ribavirin should be considered in patients with very advanced liver disease or with predictors of poor response such as failure to previous treatment.

G enotype 3 with compensated cirrhosis and / or failure of a previous treatment

Daklinza + sofosbuvir + ribavirin

24 weeks

Genotype 4

Daklinza + peg-interferon alfa + ribavirin

24 weeks of Daklinza in combination with peg-interferon alfa and ribavirin for 24-48 weeks.

If the patient has an undetectable HCV RNA level at both weeks 4 and 12 of the treatment, the 3 treatment drugs should be continued for a duration of 24 weeks. If the patient has an undetectable viral load but HCV-RNA is detectable at weeks 4 or 12 of treatment, Daklinza should be discontinued at week 24 and peg-interferon alfa and ribavirin should be continued for a total duration of 48 weeks.

* For Daklinza + sofosbuvir treatment, data for a 12-week treatment duration are only available in treatment-naive patients infected with genotype 1. For Daklinza + sofosbuvir with or without ribavirin, data are available from patients with advanced liver disease (≥ F3) without cirrhosis (see Warnings and Precautions and Pharmacodynamic Properties sections). The recommended use of Daklinza + sofosbuvir in genotype 4 is based on an extrapolation from genotype 1. For treatment with Daklinza + peg-interferon alfa + ribavirin, the data are available in treatment-naive patients (see section Properties pharmacodynamics ).

The dose of ribavirin, when combined with Daklinza, is based on weight (1000 or 1200 mg respectively in patients <75 kg or ≥ 75 kg).

Dose modification, interruption of treatment and discontinuation

It is not recommended to change the dosage of Daklinza for the management of adverse effects. If discontinuation of co-administered drugs is necessary due to adverse effects, Daklinza should not be used as monotherapy.

There are no virological response-based treatment discontinuation rules that apply to the combination of Daklinza with sofosbuvir.

Discontinuation of therapy in patients with inadequate virologic response during treatment with Daklinza, peg-interferon alfa and ribavirin

Patients with inadequate virologic response during treatment are unlikely to achieve a sustained virological response (SVR); thus, discontinuation of treatment is recommended in these patients. Thresholds for HCV RNA levels that lead to treatment discontinuation (ie, cessation of treatment rules) are presented in Table 2.

Table 2: Treatment discontinuation rules in patients receiving Daklinza in combination with peg-interferon and ribavirin with inadequate virologic response on treatment

HCV RNA level

Action

Week 4 of treatment:

> 1000 IU / ml

Stop treatment with Daklinza, peg-interferon alfa and ribavirin

Week 12 of treatment:

> 25 IU / ml

Stop treatment with Daklinza, peg-interferon alfa and ribavirin

Week 24 of treatment:

≥ 25 IU / ml

Stop treatment with peg-interferon alfa and ribavirin (week 24 corresponds to the end of Daklinza treatment)

Dosage recommendations for concomitant medications

Potent Inhibitors of Cytochrome P450 Enzyme 3A4 (CYP3A4)

The dose of Daklinza should be reduced to 30 mg once daily when co-administered with strong CYP3A4 inhibitors.

Moderate CYP3A4 inducers

The dose of Daklinza should be increased to 90 mg once daily when co-administered with CYP3A4 moderated inducers. See section Interactions with other drugs and other forms of interaction .

Missed doses

Patients should be advised that if they miss a dose of Daklinza, the missed dose should be taken as soon as possible within 20 hours of the usual set time. However, if it is missed more than 20 hours after the usual set time, the dose should be omitted and the next dose taken at the scheduled time.

Special populations

Elderly

No dose adjustment of Daklinza is required in patients ≥ 65 years of age (see sections Warnings and Precautions and Pharmacokinetic Properties ).

Insufficient enal

No dose adjustment of Daklinza is required in patients with renal impairment at any stage (see section 5.2 ).

Epic insufficiency

No dose adjustment of Daklinza is required in patients with mild (Child-Pugh A, score 5-6), moderate (Child-Pugh B, score 7-9) or severe (Child-Pugh C, score ≥ 10). Daklinza has not been studied in patients with decompensated cirrhosis (see sections Warnings and Precautions and Pharmacokinetic Properties ).

Eradiatric population

The safety and efficacy of Daklinza in children and adolescents under 18 years of age have not yet been established. No data available.

Administration mode

Daklinza should be taken orally with or without food.

Patients should be informed that they will need to swallow the tablet whole. The film-coated tablet should not be crunched or crushed because of the unpleasant taste of the active substance.

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under Composition .

Co-administration with potent inducing medications of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transporter (P-gp) that are likely to result in decreased exposure and decreased efficacy of Daklinza. These active substances include phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, dexamethasone for systemic use and St. John's wort (Hypericum perforatum).

Daklinza side effects

Summary of the security profile

The overall safety profile of daclatasvir is based on data from 798 patients with chronic HCV who received Daklinza 60 mg once daily in combination with sofosbuvir with or without ribavirin (n = 211) or combined with peg-interferon alfa and ribavirin (n = 587, pooled data), from a total of eight clinical studies.

Daklinza in combination with sofosbuvir

The most commonly reported adverse effects were fatigue, headache, and nausea. No grade 3 or 4 adverse events were reported. Two patients discontinued treatment due to adverse events, which were considered unrelated to the study.

Daklinza in combination with peg- interferon alfa and ribavirin

The most commonly reported adverse effects were: fatigue, headache, pruritus, insomnia, flu-like symptoms, dry skin, nausea, decreased appetite, alopecia, rash, asthenia, irritability, myalgia, anemia, fever, cough, dyspnoea, neutropenia, diarrhea and arthralgia. The most commonly reported adverse reactions with a grade 3 severity (greater than or equal to 1%) were neutropenia, anemia and lymphopenia. The safety profile of daclatasvir in combination with peg-interferon alfa and ribavirin was similar to that seen with peg-interferon alfa and ribavirin alone, including for patients with cirrhosis.

Summary table of adverse effects

The adverse effects presented in Table 4 are classified by organ system and frequency: very common (≥1 / 10), frequent (≥1 / 100 to <1/10), uncommon (≥1 / 1000 to <1/100), rare (≥1 / 10, 000 to <1/1000) and very rare (<1 / 10, 000). In each frequency group, adverse effects are presented in order of decreasing severity.

Table 4: Undesirable effects in clinical studies

Class of organ systems

Side effects

Fr equence

Daklinza in association with

sofosbuvir ± ribavirin *

Hematological and lymphatic system disorders

fr

an emie *

Metabolism and nutrition disorders

fr

app is decreased

Psychiatric disorders

fr

depression, anxiety, insomnia

Nervous system disorders

very common

c ephalea

fr

dizziness, migraine

Vascular disorders

fr

hot flush

Respiratory, thoracic and ediastinal disorders

fr

cough, dyspnea, exertional dyspnea, nasal congestion

Gastrointestinal disorders

very common

nausea

fr

diarrhea, high abdominal pain, constipation, flatulence, gastroesophageal reflux, dry mouth, vomiting

Skin and subcutaneous tissue disorders

fr

pruritus, dryness, alopecia, rash

Musculoskeletal and systemic disorders

fr

arthralgia, myalgia

General disorders and administration site abnormalities

very common

tired

fr

irritability

* Ninety (43%) of 211 patients received ribavirin in addition to Daklinza and sofosbuvir. In this study, there were no cases of anemia in treatment groups without ribavirin.

Biological abnormalities

In the clinical trial combining Daklinza with sofosbuvir with or without ribavirin, one patient experienced a Grade 3 hemoglobin decrease; this patient was in the ribavirin treatment group. The biological abnormalities among Daklinza-treated patients, peg-interferon alfa and ribavirin were similar to those in placebo-treated patients, peg-interferon and ribavirin.

Eradiatric population

The safety and efficacy of Daklinza in children and adolescents under 18 years of age have not yet been established. No data available.

Disclaimer of suspected adverse reactions

The statement of suspected side effects after approval of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.

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