BARACLUDE PILLS COATED 0,5MG

Latin name

BARACLUDE

Active substance

entecavir

Release form

film coated tablets

International Classification of Diseases (ICD-10)

Chronic viral hepatitis b without a delta agent

Pharmacological group

Antiviral drug

Mechanism of action

Antiviral drug, is an analogue of the nucleoside guanosine with a powerful and selective activity against the polymerase of the hepatitis B virus (HBV). Entecavir is phosphorylated to form active triphosphate with an intracellular half-life of 15 hours. The intracellular concentration of entecavir triphosphate is directly related to the extracellular level of entecavir, and there is no significant accumulation of the drug after the initial plateau level. By competing with the natural substrate, deoxyguanosine triphosphate, entecavira triphosphate inhibits all 3 functional activities of the viral polymerase: 1) HBV priming polymerase, 2) negative transcription of the pregenomic mRNA and 3) synthesis of the positive HBV DNA strand. Entecavira triphosphate is a weak inhibitor of cellular DNA polymerases α, β and δ with Ki 18-40 μM. In addition, at high concentrations of entecavir triphosphate and entecavir, no side effects were noted with respect to γ ​​polymerase and DNA synthesis in the mitochondria of HepG2 cells.

Pharmacokinetics

Suction

In healthy people, entecavir absorption is fast, Cmax in plasma is determined after 0.5-1.5 hours. When you take entecavir again in a dose of 0.1 to 1 mg, an increase in C is proportional to the dose.max and AUC. The equilibrium state is achieved after 6-10 days of ingestion 1 time / day, while the concentration in plasma increases about 2 times. Cmax and Cmin plasma equilibrium was 4.2 and 0.3 ng / ml, respectively, when taking the drug at a dose of 500 μg, 8.2 and 0.5 ng / ml, respectively, when taken at a dose of 1 mg. When ingestion of entecavir in a dose of 500 mcg, both with food with a high fat content and with low, there was a minimal delay in absorption (1-1.5 hours when taken with food and 0.75 hours when taken on an empty stomach), a decrease in Cmax by 44-46% and a decrease in AUC by 18-20%.

Distribution

Vd Entecavir exceeded the total amount of water in the body, which indicates a good penetration of the drug into the tissue.

The binding of entecavir to human plasma proteins in vitro is about 13%.

Metabolism

Entecavir is not a substrate, inhibitor or inducer of P450 isoenzymes. After the introduction of the labeled 14S-entecavir man and rats were not determined oxidized or acetylated metabolites, and the metabolites of phase II (glucuronides and sulfates) were determined in a small amount.

Removal

After reaching Cmax entecavir plasma concentrations decreased biexponentially, with T1/2 was 128-149 hours. When taken 1 time / day, there was an increase in the concentration (cumulation) of the drug by 2 times, that is, effective T1/2 was about 24 hours

Entecavir is excreted mainly by the kidneys, with 62-73% of the dose being determined in an unchanged form in the urine in the urine. Renal clearance does not depend on the dose and ranges from 360 to 471 ml / min, which indicates glomerular filtration and tubular secretion of the drug.

Indications

Chronic hepatitis B in adults with:

- compensated liver damage and the presence of viral replication, increased levels of serum transaminase activity (ALT or ACT) and histological signs of inflammation in the liver and / or fibrosis;

- decompensated liver damage.

Contraindications

- age up to 18 years;

- rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- hypersensitivity to the drug.

Side effects

From the digestive system: rarely (≥1 / 1000, <1/100) - diarrhea, dyspepsia, nausea, vomiting.

From the side of the central nervous system: often (≥1 / 100, <1/10) - headache, fatigue; rarely (≥1 / 1000, <1/100) - insomnia, dizziness, drowsiness.

Post-marketing data (frequency cannot be determined)

Immune system: anaphylactoid reaction

From the skin and subcutaneous tissue: alopecia, rash.

Liver: increased transaminase activity.

Metabolism: lactic acidosis (general fatigue, nausea, vomiting, abdominal pain, sudden weight loss, shortness of breath, rapid breathing, muscle weakness), especially in patients with decompensated liver damage.

In addition, in patients with decompensated liver damage, the following additional side effects were noted: often - a decrease in the concentration of bicarbonate in the blood, an increase in ALT activity and a concentration of bilirubin by more than 2 times compared to VGN, an albumin concentration less than 2.5 g / dl, an increase in lipase activity more than 3 times compared to the norm, platelet concentration below 50,000 / mm3; rarely - renal failure.

Overdosage

There are limited data on cases of drug overdose in patients. In healthy volunteers who received the drug in doses up to 20 mg / day for up to 14 days or in single doses up to 40 mg, there were no unexpected adverse reactions.

Treatment: overdose requires careful medical monitoring of the patient's condition. If necessary, a standard maintenance therapy.

Special notes

In the treatment of nucleoside analogues, incl. cases of lactic acidosis and severe hepatomegaly with steatosis, sometimes leading to the death of the patient, are described as entecavir, as monotherapy and in combination with antiretroviral drugs.

Symptoms that may indicate the development of lactic acidosis: general fatigue, nausea, vomiting, abdominal pain, sudden weight loss, shortness of breath, rapid breathing, muscle weakness.

Risk factors are female gender, obesity, long-term use of nucleoside analogues, hepatomegaly.If these symptoms appear or laboratory confirmation of lactic acidosis is obtained, treatment with the drug should be discontinued.

Cases of exacerbation of hepatitis after the abolition of antiviral therapy, including entecavir. Most of these cases were without treatment. However, severe exacerbations may develop, incl. fatal. The causal relationship of these exacerbations with the abolition of therapy is unknown. After cessation of treatment, it is necessary to periodically monitor the function of the liver. If necessary, antiviral therapy can be resumed.

Patients with co-hepatitis B / HIV infection

It should be borne in mind that when prescribing entecavir to patients with co-infection of HIV who are not receiving antiretroviral therapy, there is a risk of developing resistant strains of HIV. Entecavir has not been studied for the treatment of HIV infection and is not recommended for this use.

Patients with Hepatitis B Concomitant / Hepatitis C / Hepatitis D Infection

There are no data on the effectiveness of entecavir in patients with combined hepatitis B / hepatitis C / hepatitis D infections.

Patients with decompensated liver damage

There was a high risk of serious side effects from the liver, in particular, in patients with decompensated lesion of class C liver according to the Child-Pugh classification. Also, these patients are more at risk of developing lactic acidosis and such specific kidney side effects as hepatorenal syndrome.In this regard, it is necessary to carefully monitor patients for the identification of clinical signs of lactic acidosis and renal dysfunction, as well as to conduct appropriate laboratory tests in this group of patients (liver enzyme activity, blood lactic acid concentration, serum creatinine concentration).

Lamivudine-resistant patients

The presence of resistance mutations in hepatitis B virus to lamivudine increases the risk of developing resistance to entecavir. In this regard, lamivudine-resistant patients require frequent monitoring of viral load and, if necessary, an appropriate examination for the detection of resistance mutations.

Patients with impaired renal function

For patients with impaired renal function is recommended correction dosing regimen.

Patients undergoing liver transplantation.

The safety and efficacy of entecavir in patients undergoing liver transplantation are unknown. Renal function should be carefully monitored before and during entecavir treatment in patients undergoing liver transplantation and receiving immunosuppressants that may affect kidney function, such as cyclosporine and tacrolimus.

General Patient Information

Patients should be informed that entecavir therapy does not reduce the risk of transmission of hepatitis B and, therefore, appropriate precautions should be taken.

With renal failure

Have patients with renal failure Entecavir clearance decreases with decreasing QC. At QC <50 ml / min, incl. patients on hemodialysis and long-term ambulatory peritoneal dialysis, recommended dose adjustment Baraclude.

In violation of the functions of the liver

In patients with hepatic insufficiency, dose adjustment of entecavir is not required.

The elderly

Have elderly patients dose adjustment is not required.

Use during pregnancy and lactation

Adequate and well-controlled studies in pregnant women have not been conducted. Use of the drug Baraclude® during pregnancy is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Data on the removal of entecavir with breast milk is not. When using the drug, breastfeeding is not recommended.

Drug interaction

Since entecavir is excreted primarily by the kidneys, with the simultaneous administration of entecavir and drugs that cause impaired renal function or competing at the level of tubular secretion, an increase in serum concentrations of entecavir or these drugs is possible.

With the simultaneous appointment of entecavir with lamivudine, adefovir or tenofovir, no clinically significant drug interactions were detected.

The interaction of entecavir with other drugs that are excreted by the kidneys or affect kidney function has not been studied.With the simultaneous appointment of entecavir with such drugs, the patient requires careful medical supervision.

Mode of application

The drug should be taken orally on an empty stomach (ie, no less than 2 hours after a meal and no later than 2 hours before the next meal).

The recommended dose of Baracud® with compensated liver damage makes 500 mkg 1 time / days.

If you have resistance to lamivudine (i.e., if you indicate a history of viremia with the hepatitis B virus that persists during lamivudine therapy, or if you have confirmed resistance to lamivudine), it is recommended to administer entecavir at a dose of 1 mg 1 time / day.

Patients with decompensated liver damage the drug is prescribed in a dose of 1 mg 1 time / day.

Have patients with renal failure Entecavir clearance decreases with decreasing QC. At QC <50 ml / min, incl. patients on hemodialysis and long-term ambulatory peritoneal dialysis, recommended dose adjustment of the drug Baraclude® as indicated in the table.