Бараклюд®

General characteristics. Structure:

Active ingredient: 0,5 mg or 1 mg of an entekavir.

Excipients: lactoses monohydrate, cellulose microcrystallic, кросповидон, povidone, magnesium stearate, dye: opadr white (tablets of 0,5 mg) or opadra dye pink (tablets of 1,0 mg).

Composition of dye: Onadri white: titanium dioxide, gipromelloz 6 Wednesday, gipromelloza 3 Wednesday, macrogoal 400, polysorbate 80.

Composition of Onadri dye pink: gipromelloza 6 Wednesday, titanium dioxide, macrogoal 400, dye ferrous oxide red (EI72, CFR21).

Pharmacological properties:

Pharmacodynamics. Entekavir is a guanine riboside nucleoside analog with powerful and selection activity concerning HBV of a polymerase. Entekavir is phosphorylated with formation of the active triphosphate (TF) having the intracellular period of semi-life of 15 hours. Intracellular concentration of TF is directly connected with the extracellular level of an entekavir, and considerable accumulation of drug after the initial plateau level is not noted. By the competition to natural substrate, deoksiguanozina-TF, entekavira-TF inhibits all 3 functional activities of a virus polymerase: (1) priming of HBV of a polymerase, (2) reverse transcription of negative thread from pregenomny IRNK and (3) synthesis of the DNA positive HBV thread. Entekavira-TF is weak inhibitor of cellular DNA of polymerases of a, b and γ with Ki of 18-40 microns. Besides, at high concentration entekavira-TF and an entekavira side effects concerning a polymerase γ and synthesis of DNA in mitochondrions of cells of HepG2 are noted.

Pharmacokinetics. Absorption. At healthy people энтекавир it is quickly soaked up, and the maximum concentration in plasma is defined in 0,5–1,5 hours. At repeated reception of an entekavir in a dose from 0,1 to 1 mg increase in the maximum concentration (Cmax) proportional to a dose and the area under a curve "concentration – time" is noted (AUC). The equilibrium state is reached after 6-10 days of intake once a day, at the same time concentration increases in plasma approximately twice. Cmax and minimum (Cmin) of concentration in plasma in an equilibrium state made 4,2 and 0,3 ng/ml, respectively, at reception of 0,5 mg, and 8,2 and 0,5 ng/ml, respectively, at reception of 1 mg. At intake of 0,5 mg of an entekavir with food with the high content of fat or with easy food it was noted the minimum delay of absorption (1-1,5 hours at reception with food and 0,75 hours at reception on an empty stomach), decrease in Cmax by 44-46% and decrease in AUC by 18-20%.

Distribution. The estimated volume of distribution of an entekavir exceeded the total amount of water in an organism that demonstrates good penetration of drug into fabrics. Entekavir approximately for 13% contacts proteins of serum of the person of in vitro.

Metabolism and removal. Entekavir is not substrate, inhibitor or the inductor of enzymes of the CYP450 system. After introduction of a marked 14C-entekavir to people and rats the oxidized or acetylized metabolites, and phase II metabolites (glucuronides and sulfates) were not defined were defined in a small amount.

After achievement of the maximum level concentration of an entekavir in plasma decreased bieksponentsialno, at the same time the elimination half-life made 128-149 hours. At reception there was an increase in concentration (cumulation) in drug twice once a day, that is the effective elimination half-life made about 24 hours.

Entekavir is allocated mainly with kidneys, and in an equilibrium state in not changed look in urine 62% of-73% of a dose are defined. The renal clearance does not depend on a dose and fluctuates in the range from 360 to 471 ml/min. that demonstrates glomerular filtering and canalicular secretion of drug.

Indications to use:

Chronic hepatitis B at adults with:

- the compensated damage of a liver and existence of virus replication, increase in level of activity of serumal transaminases (alaninaminotranspherase, ALT; or aspartate aminotransferase, nuclear heating plant) and histologic signs of inflammatory process in a liver and/or fibrosis,

- dekompensirovanny damage of a liver.

Route of administration and doses:

Entekavir it is necessary to accept inside on an empty stomach (that is, not less than in 2 hours after food and not later than 2 hours before the following meal).

The recommended dose of an entekavir for patients with the compensated damage of a liver makes 0,5 mg once a day.

Patients, resistant to lamivudin (that is, to patients in the anamnesis with the viremiya a virus of hepatitis B remaining against the background of therapy lamivudiny or to patients with the confirmed resistance to a lamivudin) are recommended to appoint 1 mg of an entekavir once a day.

Patients with dekompensirovanny damage of a liver are recommended to appoint 1 mg of an entekavir once a day.

Patients with a renal failure. The clearance of an entekavir decreases at decrease in clearance of creatinine. Dose adjustment of an entekavir is recommended to patients with clearance of creatinine <50 ml/min., including being on a hemodialysis and long out-patient peritoneal dialysis, according to table 1.

Table 1: The recommended doses of an entekavir at patients with a renal failure.

Hemodialysis * or long out-patient peritoneal dialysis
* Entekavir it is necessary to accept after the hemodialysis session.
With a liver failure dose adjustment of an entekavir is not required from patients. Dose adjustment of an entekavir is not required from elderly patients.

Features of use:

Pregnancy and lactation. Adequate and well controlled researches at pregnant women were not conducted. BARAKLYuD has to be accepted during pregnancy, only if the potential advantage of use exceeds potential risk for a fruit.

There are no data on penetration of an entekavir into women's milk. It is not recommended to nurse at drug use.

At treatment analogs of nucleosides, including entekaviry, in the form of monotherapy and in a combination with an anti-retro - virus drugs described the cases of lactoacidosis and the expressed hepatomegalia with a steatosis sometimes leading to the death of the patient.

Symptoms which can indicate development of lactoacidosis: general fatigue, nausea, vomiting, abdominal cavity pain, sudden decrease in body weight, asthma, hurried breathing, muscular weakness. Risk factors are the female, obesity, long use of nukleozidny analogs, a hepatomegalia. At emergence of the specified symptoms or receiving a laboratory podtvezhdeniye of lactoacidosis it is necessary to stop treatment by drug.

Cases of an exacerbation of hepatitis after cancellation of antiviral therapy, including an entekavir are described. The majority of such cases passed without treatment. However heavy aggravations, including fatal can develop.

The causal relationship of these aggravations with cancellation of therapy is unknown. After the termination of treatment it is necessary to control function of a liver periodically. If necessary antiviral therapy can be resumed.

Patients with the combined hepatitis B/HIV infection. It is necessary to consider that at purpose of an entekavir to the patients with the combined infection of HIV who are not receiving anti-retrovirus therapy the risk of development of resistant strains of HIV is possible. Entekavir was not studied for treatment of HIV infection and is not recommended for similar use.

Patients with combined hepatitis B/hepatitis C/hepatitis D an infection. Patients from combined hepatitis B/hepatitis C/hepatitis D infections have no data on efficiency of an entekavir.

Patients with dekompensirovanny damage of a liver. The high risk of development of serious side effects from a liver is noted, in particular at patients with dekompensirovanny damage of a liver of a class C on classification of Chayld-Pyyu.

Also these patients are more subject to risk of development of lactoacidosis and such specific side effects from kidneys as a gepatorenalny syndrome. In this regard it is necessary to carry out careful observation of patients regarding identification of clinical signs of lactoacidosis and a renal failure, and also to carry out the corresponding laboratory analyses at this group of patients (activity of "hepatic" enzymes, concentration of lactic acid to blood, concentration of creatinine in blood serum).

Lamivudin-rezistentnye patients. Existence of mutations of stability at a hepatitis B virus to a lamivudin increases risk of development of resistance to an entekavir. In this regard carrying out frequent monitoring of virus loading and if necessary the corresponding inspection on identification of mutations of stability is required from lamivudin-resistant patients.

Patients with a renal failure. For patients with renal failures correction of the mode of dosing is recommended.

The patients who transferred transplantation of a liver. Safety and efficiency of an entekavir at the patients who transferred transplantation of a liver are unknown. It is necessary to control carefully function of kidneys before and during treatment entekaviry at the patients who transferred transplantation of a liver, and receiving immunodepressants which can influence function of kidneys, such as cyclosporine and такролимус.

General information for patients. It is necessary to inform patients that therapy entekaviry does not reduce risk of transfer of hepatitis B and therefore, the appropriate measures of precaution have to be taken.

Each tablet of drug contains 120,5 mg (a tablet of 0,5 mg) or 241 mg (a tablet of 1 mg) of lactose. In this regard administration of drug is not recommended to patients with a rare hereditary lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

Side effects:

From the alimentary system: Seldom (≥ 1/1000, <1/100): diarrhea, dyspepsia, nausea, vomiting.

From the central nervous system: Often (≥1/100, <1/10): headache, fatigue; seldom (≥ 1/1000, <1/100): sleeplessness, dizziness, drowsiness.

Post-marketing data (frequency cannot be determined):

From immune system: anaphylactoid reaction.

From skin and hypodermic cellulose: alopecia, rash.

From a liver: increase in activity of transaminases.

From a metabolism: lactoacidosis (the general fatigue, nausea, vomiting, an abdominal cavity pain, sudden decrease in body weight, an asthma, hurried breathing, muscular weakness), especially at patients with dekompensirovanny damage of a liver.

Besides, at patients with dekompensirovanny damage of a liver in addition following side effects were noted: often: decrease in concentration of bicarbonate in blood, increase in activity of ALT and concentration of bilirubin more than twice in comparison with the upper bound of norm, concentration of albumine less than 2,5 g/dl, increase of activity of a lipase more than by 3 times in comparison with norm, concentration of thrombocytes is lower than 50000/mm3; seldom: renal failure.

Interaction with other medicines:

As энтекавир it is removed preferential by kidneys, at the simultaneous introduction of an entekavir and drugs reducing function of kidneys or competing at the level of canalicular secretion, increase in concentration in serum of an entekavir or these drugs is possible.

At co-administration of an entekavir with lamivudiny, adefoviry or tenofoviry significant medicinal interactions are not revealed.

Interactions of an entekavir with other drugs, the removed kidneys or influencing function of kidneys are not studied. For patients careful medical observation at co-administration of an entekavir with such drugs has to be made.

Contraindications:

- Hypersensitivity to an entekavir or any other component of drug.

- Children's age up to 18 years.

- Rare hereditary lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

Overdose:

Patients have limited data on cases of overdose of drug. The healthy volunteers receiving up to 20 mg of drug a day during up to 14 days or single doses to 40 mg had no unexpected by-effects.

In case of overdose for the patient careful medical observation and if necessary a standard maintenance therapy has to be made.

Storage conditions:

To store at a temperature of 15-25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use drug, after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the Al/Al blister. On 3 blisters together with the application instruction in a pack cardboard.