Entecavir

Pharmacodynamics

Pharmacokinetics

Indications

With caution

Contraindications

Method of application and doses

Side effect

 

Pharmacodynamics – Antiviral agent, nucleoside analogue of guanosine with potent and selective activity against the polymerase of hepatitis B virus (HBV).

Entecavir tablet is phosphorylated to form an active triphosphate having 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 entry level of the “plateau”. By competition with the natural substrate deoxyguanosine a triphosphate, entecavir triphosphate inhibits all 3 functional activity of the viral polymerase: 1) the priming of HBV polymerase, 2) reverse transcription of the negative strands of pregenome mRNA and 3) the synthesis of positive strands of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases α, β, and δ with Ki 18-40 microns. In addition, at high concentrations, entecavir triphosphate and entecavir 0.5mg are not noted side effects on the polymerase γ and DNA synthesis in the mitochondria of HepG2 cells.

Pharmacokinetics:

In healthy people the absorption of entecavir rapid, the maximum concentration in plasma is determined through 0.5-1.5 h With repeated dose of entecavir at a dose of from 0.1 to 1 mg notes dose proportional increase in maximum concentration and AUC. The equilibrium state is achieved after 6-10 days intake 1 time per day, the plasma concentration increases approximately 2 times. The maximum concentration and the minimum plasma concentration at steady-state were 4.2 and 0.3 ng/ml, respectively while taking the drug at a dose of 500 mg, and 8.2 and 0.5 ng/ml, respectively, when taken at a dose of 1 mg. When administered entecavir at a dose of 500 mcg as a food with high fat and low, it was noted minimum delay in absorption (1-1. 5 hours when taken with food and 0.75 hours when taken on an empty stomach), reduced the maximum concentration to 44 to 46 % and decrease AUC by 18-20 %.

The equilibrium volume of entecavir dose  exceeded the total volume of water in the body, which indicates a good penetration of the drug into the tissue. Binding of entecavir with human plasma protein in vitro is approximately 13 %.

Baraclude (entecavir) is not a substrate, inhibitor or inducer of P450 isoenzyme system. After administration of labeled 14C-entekavir, oxidized or acetylated metabolites were not determined for humans and rats, and phase II metabolites (glucuronides and sulfates) were determined in small quantities.

After reaching the maximum concentration of entecavir in plasma decreased bieksponencialno, while the half-life was 128-149 h. When taking 1 every day was the increase in the concentration (accumulation) of the drug in 2 times, i.e., the effective half-life was approximately 24 h.

buy entecavir from India , Entecavir is excreted mainly by the kidneys, and in equilibrium unchanged in the urine is 62-73 % of the dose. Renal clearance does not depend on the dose and ranges from 360 to 471 ml/min, indicating glomerular filtration and canal secretion of entecavir. baraclude generic price is very low in India.

Indications:

 

Chronic hepatitis b In adults with compensated liver disease and viral replication, increase the level of activity of serum transaminases (ALT or ACT) and histological signs of inflammation in the liver and/or fibrosis; decompensated liver disease.

ICD-10

Contraindications:

 

Hypersensitivity to baraclude generic entecavir or any component of the drug; children up to age 18 years, pregnancy, lactation; liver failure.

With caution:

 

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

 

The safety and efficacy of entecavir in patients undergoing liver transplantation is unknown. You should carefully monitor renal function before and during treatment with entecavir in patients undergoing liver transplantation and receiving immunosuppressant that may affect renal function, such as cyclosporine and tacrolimus.

Pregnancy and lactation:

 

Recommendations in FDA category C. no Adequate and well-controlled studies in pregnant women have not been conducted. Application during pregnancy is possible only in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

 

Data on the excretion of generic entecavir in breast milk does not. During treatment, breast-feeding is not recommended.

Method of application and doses:

 

Take inside. The dose is 500-1000 mcg 1 time per day. The frequency of administration depends on the degree of renal dysfunction, referring to a history nucleoside therapy drugs, liver. can baraclude cure hepatitis b ? yes sure.

Side effect:

 

From the digestive system: rarely-diarrhea, dyspepsia, nausea, vomiting; possibly – increased activity of transaminases.

 

From the Central nervous system: often – headache, fatigue; rarely – insomnia, dizziness, drowsiness.

 

From the immune system: possibly – anaphylactoid reaction.

 

From the skin and subcutaneous tissue: perhaps-alopecia, rash.

 

From the metabolic: possible – lactic acidosis (General fatigue, nausea, vomiting, abdominal pain, sudden weight loss, shortness of breath, rapid breathing, muscle weakness), particularly in patients with decompensated liver disease.

 

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

Overdose:

 

Anxiety, dizziness, headache, drowsiness, lethargy, convulsions, nausea, vomiting and other manifestations of side effects.

 

In case of overdose, the patient should be carefully monitored and, if necessary, standard maintenance therapy.

Interaction:

 

Because entecavir is excreted primarily by the kidneys, with the introduction of entecavir and drugs causing impairment of renal function or compete on the level of tubular secretion may increase serum entecavir or these drugs.

 

The interaction of entecavir with other drugs that are excreted renally or affect renal function have not been studied. While the use of entecavir with such drugs should carefully monitor the patient’s condition.

Special instruction:

 

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

 

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, prolonged use of nucleoside analogues, hepatomegaly. When these symptoms or receive laboratory confirmation of lactic acidosis, discontinue treatment with the drug.

 

Described cases of acute hepatitis after the abolition of antiviral therapy, including entecavir. Most of these cases were untreated. However, severe exacerbations, including fatal ones, can develop. The causation of these exacerbations with the abolition of therapy is unknown. After the termination of treatment, it is necessary to periodically monitor the liver function. If necessary, antiviral therapy can be resumed.

 

Note that when using entecavir in patients co-infected with HIV not receiving antiretroviral therapy, the risk for the development of resistant strains of HIV. Entecavir has not been studied for the treatment of HIV infection and is not recommended for such applications.

 

There is a high risk of serious side effects from the liver, in particular, in patients with decompensated liver damage of class C according to child-Pugh classification. Also, these patients are more at risk of lactic acidosis and these specific side effects in the kidneys as hepatorenal syndrome. In this regard, you should closely monitor patients to identify the clinical features of lactic acidosis and renal dysfunction, and conduct appropriate laboratory tests in this group of patients (activity of the hepatic enzymes, the concentration of lactic acid in the blood, the creatinine concentration in the serum).

The presence of mutations stability of hepatitis b virus to lamivudine increases risk of resistance to entecavir. In this regard, lamivudine resistant patients require frequent monitoring of viral load and, if necessary, appropriate examination to detect stability mutations.

 

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