Baraclude pills coated 0,5mg N30
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Active ingredients
Entecavir
Release form
Pills
Composition
Each tablet, film coated, contains the active substance: entecavira 0.5 mg or 1.0 mg. Adjuvants: lactose monohydrate 120.5 mg or 241.0 mg, microcrystalline cellulose 65.0 mg or 130.0 mg, crospovidone 8.0 mg or 16.0 mg, Povidone K 30 5.0 mg or 10.0 mg, magnesium stearate 1.0 mg or 2.0 mg, opadry white 6.0 mg - pills 0.5 mg or opadry pink 12.0 mg - 1.0 mg pills. Composition Opadry white: titanium dioxide (31.25%), hypromellose 3 cP (29.875%), hypromellose 6cP (29.875%), macrogol 400 (8%), polysorbate 80 (1 , 0%). Composition Opadry pink: titanium dioxide (31.04%), hygrome Llose 6 cp (62.5%), macrogol 400 (6.250%), iron dye red oxide (E172, CFR21)) (0.210%).
Pharmacological effect
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
Absorption. In healthy people, entecavir is rapidly absorbed, and the maximum plasma concentration is determined after 0.5-1.5 hours. When you take entecavir at a dose of 0.1 to 1 mg, an increase in the maximum concentration (Cmax) and the area under the concentration-time curve (AUC) is observed proportional to the dose. The equilibrium state is achieved after 6-10 days of ingestion once a day, while the concentration in plasma increases about 2 times. The maximum (C max) and minimum (C min) plasma concentrations in the equilibrium state were 4.2 and 0.3 ng / ml, respectively, while taking 0.5 mg, and 8.2 and 0.5 ng / ml, respectively, while taking 1 mg.When ingestion of 0.5 mg of entecavir with food with high fat content or with light food, 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), Cmax reduction by 44-46% and a decrease in AUC by 18-20%. Distribution. Estimated volume of distribution of entecavir exceeded the total amount of water in the body, which indicates a good penetration of the drug into the tissue. Entecavir is approximately 13% bound to human serum proteins in vitro. Metabolism and excretion. Entekavir is not a substrate, inhibitor or inducer of CYP450 system enzymes. After the administration of labeled 14C-entecavir, oxidized or acetylated metabolites were not detected in humans and rats, and the metabolites of phase II (glucuronides and sulfates) were determined in a small amount. After reaching the maximum level, plasma entecavir concentration decreased biexponentially, while the half-life was 128-149 hours. When taken once a day, the concentration (cumulation) of the drug increased by 2 times, that is, the effective half-life was about 24 hours. Entekavir is excreted mainly by the kidneys, and 62% -73% of the dose is determined in an unchanged state in the urine. Renal clearance does not depend on the dose and ranges from 360 to 471 ml / min, indicating a 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 the inflammatory process in the liver and / or fibrosis; - decompensated liver damage.
Contraindications
- Hypersensitivity to entecavir or any other component of the drug. - Children under 18 years of age (efficacy and safety have not been studied). - Rare hereditary intolerance to lactose, lactase deficiency or glucose-galactose malabsorption.
Precautionary measures
Patients should be informed that entecavir therapy does not reduce the risk of transmission of hepatitis B and, therefore, appropriate precautions should be taken.
Use during pregnancy and lactation
Adequate and well-controlled studies in pregnant women have not been conducted.BARACLUDUS should be taken during pregnancy only if the potential benefit of the use exceeds the potential risk to the fetus. There is no data on the penetration of entecavir into breast milk. It is not recommended to breastfeed when using the drug.
Dosage and administration
The drug should be taken orally on an empty stomach (that is, no less than 2 hours after a meal and no later than 2 hours before the next meal). The recommended dose of Baraclude with compensated liver damage is 500 mcg 1 time / day. resistance to lamivudine (i.e. when a history of viremia is indicated by the hepatitis B virus, persisting during lamivudine therapy, or in the case of confirmed resistance to lamivudine), entecavir is recommended in a dose of 1 mg 1 time / day. Mate is prescribed in a dose of 1 mg 1 time / day. In patients with renal insufficiency, entecavir clearance decreases with decreasing CC. With CC <50 ml / min, incl. For patients on hemodialysis and long-term ambulatory peritoneal dialysis, dose adjustment of Baraclude is recommended as indicated in the table. Creatin creatinine (ml / min) - Patients not previously treated with nucleoside drugs - Patients resistant to lamivudine, and patients with decompensated liver lesions≥ 50 500 mcg 1 time / day 1 mg 1 time / day 30- <50 500 mcg every 48 h 1 mg every 48 h10- <30 500 mcg every 72 h 1 mg every 72 h <10 hemodialysis * or prolonged outpatient peritoneal dialysis 500 mcg every 5-7 days 1 mg every 5-7 days * drug cl is taking after a hemodialysis session.
Side effects
On the part of the digestive systemRedko (≥ 1/1000, <1/100): diarrhea, dyspepsia, nausea, vomiting. From the side of the central nervous system Frequently (≥ 1/100, <1/10): headache, fatigue; rarely (≥ 1/1000, <1/100): insomnia, dizziness, drowsiness.Postmarketing data (frequency cannot be determined): Immune system: anaphylactoid reactionFrom the skin and subcutaneous tissue: alopecia, rash.In the 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 deck ensirovannym liver lesions were observed in addition the following side effects: Common: decrease in blood bicarbonate concentration,the increase in ALT activity and bilirubin concentration is more than 2 times compared with the upper limit of normal, the concentration of albumin is less than 2.5 g / dl, the increase in lipase activity is more than 3 times as compared to the norm, the concentration of platelets is below 50,000 / mm3; rarely: renal failure.
Overdose
There are limited data on cases of drug overdose in patients. In healthy volunteers who received up to 20 mg of the drug per day for up to 14 days or single doses of up to 40 mg, there were no unexpected side effects. In the event of an overdose, a patient should be carefully monitored and, if necessary, standard supportive therapy.
Interaction with other drugs
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 canalicular secretion, an increase in serum concentration of entecavir or these drugs is possible. 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.
special instructions
In the treatment of nucleoside analogues, incl. cases of lactic acidosis and severe hepatomegaly with steatosis, sometimes resulting in the death of the patient. Symptoms that may indicate development of lactic acidosis: general fatigue, nausea, vomiting, abdominal pain, sudden weight loss body, shortness of breath, rapid breathing, muscle weakness. Risk factors are female gender, obesity, prolonged 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 cancellation of antiviral therapy, including, have been described. 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 combined hepatitis B / HIV infection It should be noted that the risk of developing resistant strains of HIV is possible when prescribing entecavir to patients with co-infection with HIV who are not receiving antiretroviral therapy. Entecavir has not been studied for the treatment of HIV infection and is not recommended for such use. Patients with combined hepatitis B / 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 Marked high risk of serious side effects from the liver, in particular, in patients with decompensated lesion of the liver of class C 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, careful monitoring of patients should be carried out to identify the clinical signs of lactic acidosis and renal dysfunction, as well as to conduct appropriate laboratory tests in this group of patients (liver enzyme activity, lactic acid concentration in the blood, serum creatinine concentration). Lamivududine -resistant patients The presence of resistance mutations in the hepatitis B virus to lamivudine increases the risk of developing entecavir resistance. In this regard, lamivudine-resistant patients require frequent monitoring of viral load and, if necessary, an appropriate examination to identify resistance mutations. Patients with impaired renal function For patients with impaired renal function, a dosage regimen is recommended. Patients undergoing liver transplantation. 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, which may affect kidney function,such as cyclosporine and tacrolimus. General information for patients Patients should be informed that entecavir therapy does not reduce the risk of transmission of hepatitis B and, therefore, appropriate precautions should be taken.