Generic drug of the therapeutic class: Gastro-Entero-Hepatology
Active ingredients: Daclatasvir
laboratory: Bristol Myers Squibb
Bottle of 33
Daclatasvir, used in a Cohort ATU, is indicated for the treatment of adult patients with chronic viral Infection C:
- presenting with advanced disease (with F3 / F4 liver fibrosis or with extrahepatic HCV manifestations) and for whom there are no suitable therapeutic alternatives
- Are on waiting list for liver or kidney transplant
Have undergone liver transplantation and have a recurrence of infection with hepatitis C virus.
For activity based on hepatitis C virus (HCV) genotype, see Warnings and Precautions and Pharmacodynamic Properties sections.
Dosage DACLATASVIR 60 mg Film-coated tablet Bottle of 33
Treatment with Daclatasvir should be initiated and monitored by a physician experienced in the management of patients with HCC.
The recommended dose of daclatasvir is 60 mg once daily, orally with or without food (see section 5.2 ). In some co-administrations, a dosage adjustment is necessary (see section Interactions with other medicinal products and other forms of interaction ).Daclatasvir should be used in combination with sofosbuvir 400 mg tablet (one tablet daily) for a duration of 24 weeks of treatment. Limited data from AI444040 does not support conclusion on the value of adding ribavirin to the regimen. The optimal pattern in advanced patients remains to be determined.
In patients for whom virologic rebound has been confirmed (> 1 log 10 increase in HCV viral load compared to nadir), treatment should be discontinued.
If sofosbuvir is permanently discontinued, other anti-HCV drugs should also be discontinued.
It is not recommended to change the dosage of daclatasvir for the management of adverse effects. To change the dosage of other drugs in the treatment, refer to the respective Product Characteristics Summaries.
Patients should be advised that if they miss a dose of daclatasvir, 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 time, the missed dose should not be taken and the next dose taken at the appropriate time.
No dose adjustment of daclatasvir is required in patients with end-stage renal disease (ESRD) on hemodialysis or with mild renal impairment (see section 5.2 ). A study is ongoing in patients with moderate or severe renal impairment.
No dosage adjustment of daclatasvir is required in patients with mild (Child-Pugh A, score 5-6), moderate (Child-Pugh B, score 7-9) or severe (Child-Pugh C, ≥ 10). Daclatasvir has not been studied in HCV-infected patients with decompensated cirrhosis (see section 5.2 ).
No dose adjustment of daclatasvir is required in elderly patients (see section 5.2 ).
The safety and effectiveness of daclatasvir in children and adolescents under 18 years of age have not yet been established. No data available.
Daclatasvir should be taken orally with or without food. The tablets should not be broken.
Hypersensitivity to the active substance (s) or to any of the excipients listed under Composition .
Daclatasvir is contraindicated in combination with drugs strongly inducing CYP3A4 or P - gp and therefore likely to decrease the exposure and effectiveness of aclatasvir. These active substances include phenytoin, carbamazepine, phenobarbital, rifampicin, dexamethasone, and herbal St. John's Wort (Hypericum perforatum).
Reference should be made to the respective Product Characteristics Summaries of other treatment drugs for details of their contraindications.
Daclatasvir side effects
Summary of adverse effects
The overall safety profile of daclatasvir is based on data from 716 patients with chronic HCV infection who received Daclatasvir 60 mg once daily in combination with sofosbuvir with or without ribavirin (n = 211) or with combined with peginterferon alfa and ribavirin (n = 505, pooled data) in a total of seven clinical studies.
Daclatasvir in combination with sofosbuvir
The most commonly reported adverse reactions (greater than or equal to 10%) were fatigue, headache, and nausea. The overwhelming majority of adverse events were grade 1 or 2 and two patients (<1%) discontinued treatment due to adverse events considered to be unrelated to treatment in both cases.
Daclatasvir in combination with peginterferon and ribavirin
The most commonly reported adverse reactions (greater than or equal to 10%) are listed in Table 2. Adverse reactions with at least Grade 3 severity most commonly reported (frequency ≥ 1%) were neutropenia, lymphopenia, anemia and leukopenia.
The frequency of adverse events in cirrhotic patients treated with daclatasvir / peginterferon alfa / ribavirin was similar to that observed in patients treated with pla cebo / peginterferon alfa / ribavirin (94% [50/53] vs 95% respectively [18 / 19]) and the frequency of Grade 3-4 liver abnormalities in these patients was low (less than 10% in any of the clavasavir groups).
Summary table of adverse effects
The following side effects have been reported as related to treatment with daclatasvir in combination with sofosbuvir (with or without ribavirin) or in combination with peginterferon alfa and ribavarin. In this context, no adverse effects specific to daclatasvir could be identified.
The following adverse reactions are presented in Table 2 by system organ class (SOC) and frequency: very common (≥ 1/10), common (≥ 1/100 to <1/10), infrequent (≥ 1/1000 to <1/100). In each frequency group, adverse effects are presented in order of decreasing severity.
Table 2: Adverse Reactions in Clinical Studies
Class of organ systems
Daclatasvir in combination with sofosbuvir ± ribavirin *
N = 211
Daclatasvir in combination with peginterferon alfa and ribavirin
N = 505
Infections and infestations
flu, oral herpes §, sinusitis, otitis externa, nasopharyngitis
§ pneumonia, anthrax §, furuncle §
Blood and lymphatic system disorders
anemia §, neutropenia
Leukopenia, lymphopenia, thrombocytopenia
aplastic anemia §, autoimmune haemolytic anemia §, febrile neutropenia §
Metabolism and nutrition disorders
Depression §, insomnia
depression, anxiety, insomnia
anxiety, depressed mood, altered mood, sleep disorder, mood disorders, decreased libido
schizophrenia, paranoid type §
Nervous system disorders
dizziness, disturbances of attention, memory problems, tremor, hypoesthesia, lethargy, dysgeusia, poor sleep, restless legs syndrome
O Phthalmological conditions
eye pruritus, blurred vision, dry eye, eye irritation, eye pain, decreased visual acuity
retinal hemorrhage §
Affections of the ear and labyrinth
Respiratory, thoracic and mediastinal disorders
cough, dyspnea, exertional dyspnea, nasal congestion
exercise dyspnea, nasal congestion, oropharyngeal pain, epistaxis, productive cough
diarrhea e, upper abdominal pain, constipation, flatulence, gastroesophageal reflux, dry mouth, vomiting
abdominal pain, constipation, flatulence, gastroesophageal reflux, dry mouth, vomiting, abdominal discomfort, dyspepsia, stomatitis, abdominal discomfort, abdominal pain, oral ulcer, stomatitis, cheilitis
anal fissure §, gastrointestinal inflammation §
A ffections of the skin and subcutaneous tissue
pruritus, dry skin, alopecia, rash
pruritus, dry skin, alopecia, rash
erythema, hyperhidrosis, generalized pruritus, dermatitis, eczema, night sweats, maculopapular rash, skin fissures, skin lesion
Musculoskeletal and systemic disorders
back pain, muscle contractures, painful extremities
General disorders and administration site conditions **
fatigue, flu-like pathology §, irritability, asthenia, pyrexia
irritability, abnormal taste of the product
chills, pain, sensation of abnormal state, malaise, dryness of the mucosa
Streptococcus positive test §
* Ninety (43%) of the 211 patients received ribavirin in addition to daclatasvir and sofosbuvir. In this study, there were no cases of anemia in treatment groups without ribavirin.
§ Includes adverse events assessed as serious by the investigator in subjects in clinical studies.
** Injection site reactions are not included since daclatasvir is administered orally.
Table 4 presents the selected laboratory abnormalities under treatment (Grade 3-4 toxicity according to WHO criteria) that were observed in HCV-infected patients treated with daclatasvir combination therapy, depending on the treatment. associated.
Table 4: Biological abnormalities developed during treatment (Grade 3-4 toxicity according to WHO criteria) ‡ observed in patients infected with HCV
|Daclatasvir in combination with sofosbuvir ± ribavirin *||Daclatasvir in combination with peginterferon alfa and ribavirin|
|N = 211||N = 505|
|Biological parameters||Percentage presenting the anomaly||Percentage presenting the anomaly|
Hepatoglobin Reduction, Grade 3-4
Thrombocytopenia Grade 3-4
Neutropenia Grade 3-4
ALT increase, Grade 3-4
Increase ASAT Grade 3-4
Increased Bilirubin, Grade 3-4
* Ninety (43%) of the 211 patients received ribavirin in addition to daclatasvir and sofosbuvir. In this study, there were no cases of Grade 3-4 hemoglobin decline in treatment groups without ribavirin.
‡ The severity grades of the biological results were evaluated using the Adverse Reaction Severity Score Chart in adult and pediatric patients from the "AIDS Division" ("DAIDS Adverse Event Evaluation Table"). ), Version 1.0.
Declaration of adverse effects
It is necessary to pay particular attention to any adverse effects that may occur in the context of the cohort ATU. In this context, the reporting of adverse effects is important given the limited decline in clinical data at this stage of development of the drug. It allows continuous monitoring of the benefit / risk ratio of the drug. Healthcare professionals must report any suspected adverse reactions using the corresponding sheet (see Annex D) of the Therapeutic Use and Information Collection Protocol (TUP).