BARAKLYUD

Active material: Entecrair
When ATH: J05aa
CCF: Viricide
ICD-10 codes (testimony): B18.1
When CSF: 09.01.01
Manufacturer: BRISTOL-MYERS SQUIBB Company (United States)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white or nearly white, Triangular, labeled “BMS” on one side and “1611” on the other side.

Excipients: lactose monohydrate, microcrystalline cellulose, krospovydon, povidone, magnesium stearate, The dye is white.

10 PC. – blisters (3) – packs cardboard.

Pills, Film-coated Pink colour, Triangular, labeled “BMS” on one side and “1612” on the other side.

Excipients: lactose monohydrate, microcrystalline cellulose, krospovydon, povidone, magnesium stearate, The dye is pink.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Viricide, It is an analogue of Nucleoside Guanosin with powerful and selective activity regarding the polymerase of the hepatitis B virus (HBV). Entecavir phosphoriles with the formation of active triphosphate (TF), having an intracellular period of half -life 15 no. The intracellular concentration of TF is directly related to the extracellular level of the Entecavir, Moreover, there is no significant accumulation of the drug after the initial level “plateau”. By competition with a natural substrate, Deoxiguanosina-TF, Entkavira-TF inhibits everything 3 functional activity of viral polymerase: (1) priming HBV Polymera, (2) reverse transcription of a negative thread from the Permenomic IRNK and (3) Positive thread synthesis HBV DNA. Entkavira-TF is a weak inhibitor of cellular DNA polymeras α, b и с с ki 18-40 M. Besides, At high concentrations of Entkavir-TR and Entekavir, side effects were not noted against γ polymerase and DNA synthesis in HEPG2 cell mitochondria.

Pharmacokinetics

Absorption

In healthy people, the absorption of Entecavir fast, C_max In blood plasma is determined through 0.5-1.5 no. With repeated intake of Entecavir at the dose from 0.1 to 1 mg notes a proportional dose of increase c_max и AUC. The equilibrium state is achieved after 6-10 Days of admission inside 1 time / day, In this case, the concentration in plasma increases approximately in 2 times. C_max and C_min In plasma in equilibrium, they made up 4.2 and 0.3 ng/ml, respectively, when taking the drug at the dose 500 g, 8.2 and 0.5 ng / ml, respectively, upon receiving a dose 1 mg. When taking the entkiri in the dose 500 mcg like with a high fat content, and with low marked a minimum delay in absorption (1-1.5 h when intake with food and 0.75 h when taking on an empty stomach), decrease in C_max on 44-46% and a decline AUC of 18-20%.

Distribution

V_d Entecavir exceeded the total volume of water in the body, which indicates good penetration of the drug into tissue.

Binding by Entecavir to human plasma proteins in vitro is about 13%.

Metabolism

Entkavir is not a substrate, inhibitor or inducer of systems of the P450 system. After the introduction of the mentioned ¹⁴S-Entekavira did not determine oxidized or acetylated metabolites to man and rats, and phase II metabolites (glucuronide and sulfate) Determined in a small amount.

Deduction

After reaching C_max The concentration of the Entecavir in plasma decreased biexponces, wherein T_1/2 was 128-149 no. At reception 1 Once/day there was an increase in concentration (cumulation) drug in 2 times, That is, an effective t_1/2 Compiled approximately 24 no.

Entkavir is mainly displayed by the kidneys, Moreover, in equilibrium, in unchanged form in the urine is determined 62-73% dose. The renal clearance does not depend on the dose and fluctuates in the range from 360 to 471 ml / min, which indicates glomerular filtration and channel secretion of the drug.

Testimony

- chronic hepatitis B in adults with signs of viral replication and an increase in the level of activity of serum transaminases (ALT or ACT) or in the presence of histological signs of the inflammatory process in the liver.

Dosage regimen

The drug should be taken inside on an empty stomach (i.e, not less than 2 h after eating and no later, than 2 h until the next meal).

The recommended dose of the drug Baradlid is 500 g 1 time / day. In the presence of resistance to lamivudin (ie. when indicating a history of viremia hepatitis B virus, preserved against the background of therapy by lamivudine, or in the case of confirmed resistance to lamivudin) It is recommended to prescribe entkavir in the dose 1 mg 1 time / day.

In patients with renal insufficiency Entecavir clearance decreases with a decrease in KC. At CC <50 ml / min, incl. patients, on hemodialysis and prolonged outpatient peritoneal dialysis, Recommended by correction of correction Baraklyud as reporting in the table.

Recommended doses of entekavir in patients with renal insufficiency

*Entkavir should be taken after a hemodialysis session.

In Patients with liver failure dose correction of entekavir is not required.

Side effect

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

CNS: often (≥ 1/100, < 1/10) – headache, fatiguability; rarely (≥1/1000, < 1/100) – insomnia, dizziness, drowsiness.

Post-marketing data (The frequency cannot be determined)

Allergic reactions: anaphylactoid reactions.

Dermatological reactions: alopecia, rash.

Contraindications

- Up to 18 years;

- increased sensitivity to entkavir or any other component of the drug.

Pregnancy and lactation

Adequate and well -controlled clinical studies of the safety of the drug during pregnancy were not carried out. The use of the drug Baradlid during pregnancy is possible only in cases, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Unknown, whether the entkavir with breast milk in humans stands out. When using the drug, breastfeeding is not recommended.

Cautions

In the treatment of nucleosides in the form of monotherapy and in combination with antiretroviral drugs, cases of lactacidosis and pronounced hepatomegaly with steatosis are described, sometimes led to the death of the patient.

Cases of exacerbation of hepatitis after the abolition of antiviral therapy are described, incl. Entecavira. Most of these exacerbations took place without treatment. However, severe exacerbations may develop, incl. Fatal. The causal relationship of these exacerbations with the abolition of therapy has not been established. After the cessation of treatment, it is necessary to periodically monitor the liver function. If necessary, antiviral therapy can be renewed.

It should be taken into account, that when prescribing an entkavir to patients in the case of a combined HIV infection, previously not received highly active antiretroviral therapy, the risk of developing stable HIV strains is possible. Entkavir was not studied for the treatment of HIV infection and is not recommended for use in such cases.

Entecavir safety and efficiency in patients, Transferred liver transplantation, unknown. The kidney function should be carefully monitored before and during the treatment of Entecavir in patients, Transferred liver transplantation, and receiving immunosuppressants, which can affect the function of the kidneys, such as cyclosporin and takrolimus.

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

Overdose

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

Treatment: With an overdose, careful medical monitoring of the patient's condition is required. If necessary, standard supporting therapy is carried out.

Drug Interactions

Since Entecavir is excreted mainly by the kidneys, With the simultaneous administration of entekavir and drugs, causing impaired renal function or competing at the level of tubular secretion, it is possible to increase the concentration in the serum of the entecavir or these drugs.

With the simultaneous appointment of Entekavir with lamivudin, Adefovir or tenofovir did not reveal clinically significant drug interaction. Entecavir interaction with other drugs, which are excreted by the kidneys or affect the function of the kidneys, not known. With the simultaneous prescription of Entecavir with such drugs, the patient needs careful medical observation.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, at a temperature no higher than 25 ° C. Shelf life – 2 year.