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Daklinza is a brand name for Daclatasvir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Daklinza is indicated in combination with other medicinal products for the treatment of chronic hepatitis C virus (HCV) infection in adults (see sections 4.2, 4.4 and 5.1). For HCV genotype specific activity, see sections 4.4 and 5.1.
Verbatim from this product's EMA label. Tap a section to expand.
Medicinal product no longer authorised 3 Posology The recommended dose of Daklinza is 60 mg once daily, to be taken orally with or without meals. Daklinza 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 Daklinza.
1) GT: Genotype; CP: Child Pugh * Includes patients co-infected with human immunodeficiency virus (HIV). 5. Daklinza + peginterferon alfa + ribavirin This regimen is an alternative recommended regimen for patients with genotype 4 infection, without cirrhosis or with compensated cirrhosis.
Daklinza is given for 24 weeks, in combination with 24-48 weeks of peginterferon alfa and ribavirin: - If HCV RNA is undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks.
Medicinal product no longer authorised 4 Ribavirin Dosing Guidelines The dose of ribavirin, when combined with Daklinza, is weight-based (1,000 or 1,200 mg in patients <75 kg or ≥75 kg, respectively). Refer to the Summary of Product Characteristics of ribavirin.
For patients with Child-Pugh A, B, or C cirrhosis or recurrence of HCV infection after liver transplantation, the recommended initial dose of ribavirin is 600 mg daily with food. If the starting dose is well-tolerated, the dose can be titrated up to a maximum of 1,000-1,200 mg daily (breakpoint 75 kg).
If the starting dose is not well-tolerated, the dose should be reduced as clinically indicated, based on haemoglobin and creatinine clearance measurements (see Table 2). 5 g/dL Discontinue ribavirin Creatinine Clearance >50 mL/min Follow guidelines above for haemoglobin >30 to ≤50 mL/min 200 mg every other day ≤30 mL/min or haemodialysis Discontinue ribavirin Dose modification, interruption and discontinuation Dose modification of Daklinza to manage adverse reactions is not recommended.
If treatment interruption of components in the regimen is necessary because of adverse reactions, Daklinza must not be given as monotherapy. There are no virologic treatment stopping rules that apply to the combination of Daklinza with sofosbuvir.
Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with Daklinza, peginterferon alfa and ribavirin It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR); therefore discontinuation of treatment is recommended in these patients.
Summary of the safety profile The overall safety profile of daclatasvir is based on data from 2215 patients with chronic HCV infection who received Daklinza once daily either in combination with sofosbuvir with or without ribavirin (n=679, pooled data) or in combination with peginterferon alfa and ribavirin (n=1536, pooled data) from a total of 14 clinical studies.
Daklinza in combination with sofosbuvir The most frequently reported adverse reactions were fatigue, headache, and nausea. Grade 3 adverse reactions were reported in less than 1% of patients, and no patients had a Grade 4 adverse reaction.
Four patients discontinued the Daklinza regimen for adverse events, only one of which was considered related to study therapy. Daklinza in combination with peginterferon alfa and ribavirin The most frequently reported adverse reactions were fatigue, headache, pruritus, anaemia, influenza- like illness, nausea, insomnia, neutropenia, asthenia, rash, decreased appetite, dry skin, alopecia, pyrexia, myalgia, irritability, cough, diarrhoea, dyspnoea and arthralgia.
The most frequently reported adverse reactions of at least Grade 3 severity (frequency of 1% or greater) were neutropenia, anaemia, lymphopenia and thrombocytopenia. The safety profile of daclatasvir in combination with peginterferon alfa and ribavirin was similar to that seen with peginterferon alfa and ribavirin alone, including among patients with cirrhosis.
Tabulated list of adverse reactions Adverse reactions are listed in Table 5 by regimen, system organ class and frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000)Medicinal product no longer authorised 18 and very rare (<1/10,000).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Daklinza must not be administered as monotherapy. 2). Severe bradycardia and heart block Cases of severe bradycardia and heart block have been observed when Daklinza is used in combination with sofosbuvir and concomitant amiodarone with or without other drugs that lower heart rate.
The mechanism is not established. The concomitant use of amiodarone was limited through the clinical development of sofosbuvir plus direct-acting antivirals (DAAs). Cases are potentially life threatening, therefore amiodarone shouldMedicinal product no longer authorised 6 only be used in patients on Daklinza and sofosbuvir when other alternative antiarrhythmic treatments are not tolerated or are contraindicated.
Should concomitant use of amiodarone be considered necessary it is recommended that patients are closely monitored when initiating Daklinza in combination with sofosbuvir. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for 48 hours in an appropriate clinical setting.
Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on Daklinza in combination with sofosbuvir.
All patients receiving Daklinza and sofosbuvir in combination with amiodarone with or without other drugs that lower heart rate should also be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.
2. 1. Data to support the treatment of genotype 2 infection with Daklinza and sofosbuvir are limited. Data from study ALLY-3 (AI444218) support a 12-week treatment duration of Daklinza + sofosbuvir for treatment-naïve and -experienced patients with genotype 3 infection without cirrhosis.
1). Data from compassionate use programmes which included patients with genotype 3 infection and cirrhosis, support the use of Daklinza + sofosbuvir for 24 weeks in these patients. 1). The clinical data to support the use of Daklinza and sofosbuvir in patients infected with HCV genotypes 4 and 6 are limited.
1. Coadministration with medicinal products that strongly induce cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transporter (P-gp) and thus may lead to lower exposure and loss of efficacy of Daklinza. These active substances include but are not limited to phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St John’s wort (Hypericum perforatum).
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e. treatment stopping rules) are presented in Table 3.
Table 3:
Treatment stopping rules in patients receiving Daklinza in combination with peginterferon alfa and ribavirin with inadequate on-treatment virologic response HCV RNA Action Treatment week 4: >1000 IU/ml Discontinue Daklinza, peginterferon alfa and ribavirin Treatment week 12: ≥25 IU/ml Discontinue Daklinza, peginterferon alfa and ribavirin Treatment week 24: ≥25 IU/ml Discontinue peginterferon alfa and ribavirin (treatment with Daklinza is complete at week 24) Dose recommendation for concomitant medicines Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4)Medicinal product no longer authorised 5 The dose of Daklinza should be reduced to 30 mg once daily when coadministered with strong inhibitors of CYP3A4.
Moderate inducers of CYP3A4 The dose of Daklinza should be increased to 90 mg once daily when coadministered with moderate inducers of CYP3A4. 5. Missed doses Patients should be instructed that, if they miss a dose of Daklinza, 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. 2). 2). Hepatic impairment No dose adjustment of Daklinza is required for patients with mild (Child-Pugh A, score 5-6), moderate (Child-Pugh B, score 7-9) […]
Table 5:
Adverse reactions in clinical studies System Organ Class Adverse Reactions Frequency Daklinza +sofosbuvir + ribavirin N=203 Daklinza +sofosbuvir N=476 Blood and lymphatic system disorders very common anaemia Metabolism and nutrition disorders common decreased appetite Psychiatric disorders common insomnia, irritability insomnia Nervous system disorders very common headache headache common dizziness, migraine dizziness, migraine Vascular disorders common hot flush Respiratory, thoracic and mediastinal disorders common dyspnoea, dyspnoea exertional, cough, nasal congestion Gastrointestinal disorders very common nausea common diarrhoea, vomiting, abdominal pain, gastrooesophageal reflux disease, constipation, dry mouth, flatulence nausea, diarrhoea, abdominal pain Skin and subcutaneous tissue disorders common rash, alopecia, pruritus, dry skin Musculoskeletal and connective tissue disorders common arthralgia, myalgia arthralgia, myalgia General disorders and administration site conditions very common fatigue fatigue Laboratory abnormalities In clinical studies of Daklinza in combination with sofosbuvir with or without ribavirin, 2% of patients had Grade 3 haemoglobin decreases; all of these patients received Daklinza + sofosbuvir + ribavirin.
Grade 3/4 increases in total bilirubin were observed in 5% of patients (all in patients with HIV co- infection who were receiving concomitant atazanavir, with Child-Pugh A, B, or C cirrhosis, or who were post-liver transplant). 5). Paediatric population The safety and efficacy of Daklinza in children and adolescents aged <18 years have not yet been established.
Medicinal product no longer authorised 19 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
1). Patients with Child-Pugh C liver disease The safety and efficacy of Daklinza in the treatment of HCV infection in patients with Child-Pugh C liver disease have been established in the clinical study ALLY-1 (AI444215, Daklinza + sofosbuvir + ribavirin for 12 weeks); however, SVR rates were lower than in patients with Child-Pugh A and B.
1). Ribavirin may be added based on clinical assessment of an individual patient. HCV/HBV (hepatitis B virus) co-infection Cases of hepatitis B virus (HBV) reactivation, some of them fatal, have been reported during or after treatment with direct-acting antiviral agents.
HBV screening should be performed in all patients before initiation of treatment. HBV/HCV co-infected patients are at risk of HBV reactivation, and should therefore be monitored and managed according to current clinical guidelines. Retreatment with daclatasvir The efficacy of Daklinza as part of a retreatment regimen in patients with prior exposure to a NS5A inhibitor has not been established.
Pregnancy and contraception requirements Daklinza should not be used during pregnancy or in women of childbearing potential not using contraception. 6). When Daklinza is used in combination with ribavirin, the contraindications and warnings for that medicinal product are applicable.
Medicinal product no longer authorised 7 Interactions with medicinal products Coadministration of Daklinza can alter the concentration of other medicinal products and other medicinal products may alter the concentration of daclatasvir.
3 for a listing of medicinal products that are contraindicated for use with Daklinza due to potential loss of therapeutic effect. 5 for established and other potentially significant drug-drug interactions. Use in diabetic patients Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV DAA treatment.
Glucose levels of diabetic patients initiating DAA therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when DAA therapy is initiated.
Paediatric population Daklinza is not recommended for use in children and adolescents aged below 18 years because the safety and efficacy have not been established in this population. Important information about some of the ingredients in Daklinza Daklinza contains lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Patients on controlled sodium diet Daklinza contains less than 1 mmol sodium […]