Medicinal Products

BARACLUDE 005 mg / ml

Generic drug of the therapeutic class: Gastro-Entero-Hepatology
active ingredients: Entecavir, Entecavir
laboratory: Bristol Myers Squibb

Drinkable solution
box of 1 bottle of 210 ml
All forms

Indication

Baraclude is indicated for the treatment of adult patients with chronic infection with the hepatitis B virus (HBV) (see section 5.1 ).

■ compensated liver disease with evidence of active viral replication, persistent elevation of serum alanine aminotransferase (ALT) levels, histologically proven active liver inflammation and / or fibrosis.

■ Decompensated liver disease (see Warnings and Precautions section ).


For compensated and decompensated liver diseases, the indication is based on data from clinical studies in HBeAg-positive nucleoside-naive patients and HBeAg-negative HBeAg patients. For patients with lamivudine-resistant HBV, see section 4.2 Posology and method of administration, Warnings and precautions for use, and Pharmacodynamic properties.


Baraclude is also indicated for the treatment of chronic HBV infection in naïve nucleoside-treated pediatric patients aged 2 years to less than 18 years with compensated liver disease with evidence of active viral replication. persistent elevation of serum ALT levels or moderate to severe hepatic inflammation and / or histologically proven fibrosis. To initiate the treatment of pediatric patients, see sections Posology and method of administration, Warnings and precautions for use and Pharmacodynamic properties .

Dosage BARACLUDE 005 mg / ml oral solution box of 1 bottle of 210 ml

Baraclude is indicated for the treatment of adult patients with chronic infection with the hepatitis B virus (HBV) (see section 5.1 ).

■ compensated liver disease with evidence of active viral replication, persistent elevation of serum alanine aminotransferase (ALT) levels, histologically proven active liver inflammation and / or fibrosis.

■ Decompensated liver disease (see Warnings and Precautions section ).


For compensated and decompensated liver diseases, the indication is based on data from clinical studies in HBeAg-positive nucleoside-naive patients and HBeAg-negative HBeAg patients. For patients with lamivudine-resistant HBV, see section 4.2 Posology and method of administration, Warnings and precautions for use, and Pharmacodynamic properties.


Baraclude is also indicated for the treatment of chronic HBV infection in naïve nucleoside-treated pediatric patients aged 2 years to less than 18 years with compensated liver disease with evidence of active viral replication. persistent elevation of serum ALT levels or moderate to severe hepatic inflammation and / or histologically proven fibrosis. To initiate the treatment of pediatric patients, see sections Posology and method of administration, Warnings and precautions for use and Pharmacodynamic properties .

Against indications

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

Baraclude side effects

at. Summary of the job security profile

In clinical studies in patients with compensated liver disease, the most common adverse effects, regardless of severity, with at least one causal relationship to entecavir, are headache (9%), fatigue (6%), dizziness (4%) and nausea (3%). Exacerbations of hepatitis during and after stopping treatment with entecavir have also been reported (see Warnings and Precautions and (c) Description of Specific Adverse Reactions).

b. Table summarizing the adverse effects

The adverse reaction assessment is based on the experience gained since the drug's launch and four clinical trials in which 1, 720 patients with chronic hepatitis B infection and compensated liver disease received double-blind treatment with entecavir (n = 862) or lamivudine (n = 858) for up to 107 weeks (see section 5.1 ). In these studies, safety profiles, including laboratory abnormalities, were comparable for entecavir 0.5 mg once daily (679 HBeAg positive or negative patients who had never received treatment with a nucleoside analogue, treated with average duration of 53 weeks), entecavir 1 mg once daily (183 lamivudine-resistant patients treated for an average of 69 weeks) and lamivudine.

Adverse reactions considered to be attributable to treatment with entecavir are listed below by organ class. Frequency is defined as: very common (≥ 1/10); frequent (≥ 1/100 to <1/10); uncommon (≥ 1 / 1, 000 to <1/100); rare (≥ 1 / 10, 000 to <1 / 1, 000). Within each group frequency, adverse effects should be presented in order of decreasing severity.
























Immune system disorders:

rare: anaphylactoid reaction

Psychiatric disorders:

frequent: insomnia

Nervous system disorders:

frequent: headache, dizziness, drowsiness

Gastrointestinal disorders:

frequent: vomiting, diarrhea, nausea, dyspepsia

Hepatobiliary disorders

frequent: increased transaminases

Skin and subcutaneous tissue disorders

uncommon: rash, alopecia

General disorders and administration site defects:

frequent: tiredness

Cases of lactic acidosis have been reported, often in combination with hepatic decompensation, other serious medical conditions or drug exposures (see Warnings and Precautions for Use section ).

Treatment beyond 48 weeks: continuous treatment with entecavir for an average of 96 weeks did not show any changes in the safety profile of entecavir.

c. Description of some specific adverse effects


Biological abnormalities: In clinical trials in patients who have never received treatment with a nucleoside analogue, 5% of patients had ALT elevations> 3 times the baseline, and 2 times the baseline with total bilirubin> 2 times the upper limit of normal (ULN) and> 2 times the baseline. Albumin levels <2.5 g / dl occurred at 3 times baseline, 11% lipase> 3 times baseline, and <1% of patients had platelet counts <50, 000 / mm 3 .

In clinical trials in lamivudine-resistant patients, 4% of patients had an elevation of ALT> 3 times the baseline, and twice the baseline with total bilirubin> 2 times ULN and> 2 times the baseline. initial level. 2% of patients had amylasemia> 3 times baseline, 18% had lipase> 3 times baseline, and <1% had platelet counts <50, 000 / mm3.

Exacerbations during treatment: in studies in patients who have never received treatment with a nucleoside analogue, an increase in ALT under treatment> 10 times ULN and

> 2 times the initial level was observed in 2% of patients treated with entecavir versus 4% of patients treated with lamivudine. In studies with lamivudine-resistant patients, an elevation of> 10 times ULN and> 2 times the baseline was observed in 2% of patients treated with entecavir versus 11% of patients treated with lamivudine . Among the patients treated with entecavir, an elevation of ALT under treatment was observed after a mean time of 4-5 weeks and generally gave way with the continuation of treatment, and in most cases this elevation has been associated with a reduction in viral load ≥ 2 log 10 / ml, before or at the same time as the increase in ALAT. Periodic control of liver function is recommended during treatment.


Exacerbations after discontinuation of treatment: Acute exacerbations of hepatitis have been reported in patients who discontinued anti-hepatitis B therapy, including treatment with entecavir (see Warnings and Precautions section ) . In studies in nucleoside-naive patients, 6% of entecavir-treated patients and 10% of lamivudine-treated patients experienced elevations of ALT (> 10-fold ULN and> 2-fold baseline [minimum value between the initial value and the value of the latest biological analyzes]) during post-treatment follow-up. Among the nucleoside-naive patients treated with entecavir, an ALT elevation occurred on average 23 to 24 weeks after stopping treatment, and 86% (24/28) of these elevations of ALAT occurred in negative HBeAg patients. In studies in lamivudine-resistant patients, with a limited number of patients being followed, 11% of patients treated with entecavir and none of the patients treated with lamivudine developed an ALT increase during post-treatment follow-up. .

In clinical studies, treatment with entecavir has been discontinued in patients achieving a predefined response. If treatment is discontinued for any reason other than a response to treatment, the frequency of ALT increases after treatment may be higher.

d. Pediatric population

The safety of entecavir in pediatric patients aged 2 years to less than 18 years old is based on two ongoing clinical studies in subjects with chronic HBV infection: a Phase 2 pharmacokinetic study (Study 028). ) and a Phase 3 study (Study 189). These studies provide data from 195 Ag-HBe positive, nucleoside-treatment-naive subjects treated with entecavir over a median of 99 weeks. Adverse events observed in pediatric patients treated with entecavir are consistent with those observed in adult entecavir clinical studies (see Safety Summary Summary and Pharmacodynamic Properties section). ).

e. Other special populations


Data in patients with decompensated liver disease: The safety profile in patients with decompensated liver disease was evaluated in a randomized, open-label comparative study in patients receiving entecavir 1 mg / day (n = 102) or adefovir dipivoxil 10 mg / day (n = 89) (study 048). Regarding the side effects listed in section b. Summary table of adverse events, an additional adverse effect [decreased blood bicarbonate levels (2%)] was observed in patients treated with entecavir for 48 weeks. The cumulative mortality rate in the study was 23% (23/102) and the causes of death were generally related to liver function, as expected in this patient population. The cumulative rate of hepatocellular carcinoma (HCC) in the study was 12% (12/102). Serious adverse events were generally related to the liver with a cumulative frequency during the study of 69%. Patients with a high CPT score at the start of the study were at a higher risk of developing serious side effects

(see section Warnings and precautions for use ).

Biological abnormalities: At 48 weeks, among patients treated with entecavir and with decompensated liver disease, none had elevations of ALT both> 10 times ULN and> 2 times baseline and 1% of patients had Elevations of ALT> 2 times baseline with total bilirubin> 2 times ULN and> 2 times baseline. Albumin levels 3 times the initial level in 10% and platelets <50, 000 / mm 3 in 20%.


Data in patients co-infected with HIV: the safety profile of entecavir in a limited number of patients co-infected with HIV and HBV under HAART (Highly Active Antiretroviral Therapy) containing lamivudine was similar to Tolerance profile of HBV mono-infected patients (see Warnings and Precautions section ).


Age / sex: No difference in entecavir safety profile was observed according to sex (~ 25% of women in clinical trials) or age (~ 5% of patients were> 65 years old ).


Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorization 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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