Baraclud, 1 mg 30 pcs

Pharmgroup:

Antiviral drug.

Pharmic action:

Baraclud is an antiviral drug and is an analog of guanosine nucleoside with potent and selective activity against hepatitis B virus (HBV) polymerase.

Entecavir is phosphorylated to form active triphosphate (TF), which has an intracellular half-life of 15 h. The intracellular TF concentration 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 its natural substrate, deoxyguanosine-TF, entecavir-TF inhibits all 3 functional activities of viral polymerase: (1) HBV polymerase priming, (2) reverse transcription of negative strand from pregenomic iRNA and (3) synthesis of positive strand HBV DNA. Entecavir-TF is a weak inhibitor of cellular DNA polymerases α, β and δ with a Ki of 18-40 μM. In addition, at high concentrations of entecavir-TF and entecavir, no adverse effects were noted with respect to γ polymerase and DNA synthesis in mitochondria of HepG2 cells.

Pharmacokinetics:

Absorption

In healthy subjects, absorption of entecavir is rapid, with Cmax in plasma determined after 0.5-1.5 h. When entecavir is taken repeatedly at a dose of 0.1 to 1 mg, a dose-proportional increase in Cmax and AUC is noted. The equilibrium state is reached after 6-10 days of oral administration once daily, with a plasma concentration increase of about 2-fold. Cmax and Cmin in plasma at equilibrium were 4.2 and 0.3 ng/ml, respectively, when administered in 500 mcg dose, 8.2 and 0.5 ng/ml, respectively, when administered in 1 mg dose. In oral administration of entecavir at a dose of 500 mcg with both high and low fat foods, minimal delay in absorption (1-1.5 h when taken with food and 0.75 h when taken on an empty stomach), a decrease in Cmax by 44-46% and a decrease in AUC by 18-20% were observed.

Distribution

The Vd of entecavir exceeded total body water, indicating good tissue penetration of the drug.
The in vitro binding of entecavir to human plasma proteins is about 13%.

Metabolism

Entecavir is not a substrate, inhibitor or inducer of P450 isoenzymes. No oxidized or acetylated metabolites were detected after administration of labeled 14C-entecavir to humans and rats, and few phase II metabolites (glucuronides and sulfates) were detected.

Elimation

After reaching Cmax, the plasma concentration of entecavir decreased biexponentially, with a T1/2 of 128-149 h. When taken once daily. concentration (cumulation) of the drug increased twofold, i.e. effective T1/2 was approximately 24 h.
Entecavir is excreted primarily by the kidneys, with 62-73% of the dose in the urine unchanged in the equilibrium state. Renal clearance is independent of dose and ranges from 360 to 471 mL/min, indicating glomerular filtration and tubular secretion of the drug.

Indications

Chronic hepatitis B in adults with signs of viral replication and elevated serum transaminase activity (ALT or AST) or with histological signs of liver inflammation.

Active ingredient

Composition

1 tablet contains entecavir 1 mg.

How to take, the dosage

Baraclud should be taken orally on an empty stomach (that is, at least 2 hours after a meal and no later than 2 hours before the next meal).

The recommended dose of entecavir is 0.5 mg once daily.

Lamivudine-resistant patients (that is, patients with a history of hepatitis B virus viremia persisting on lamivudine therapy or patients with confirmed lamivudine resistance) are recommended to receive 1 mg of entecavir once daily.

Patients with renal impairment: the clearance of entecavir decreases as creatinine clearance decreases.

The dose adjustment of entecavir is recommended for patients with creatinine clearance < 50 ml/min, including those on hemodialysis and long-term ambulatory peritoneal dialysis. Entecavir should be taken after a hemodialysis session.

In patients with hepatic impairment, there is no need to adjust the dose of entecavir.

Interaction

Because entecavir is primarily excreted by the kidneys, concomitant administration of entecavir and drugs that reduce renal function or compete at the level of tubular secretion may increase serum concentrations of entecavir or these drugs.

No significant drug interactions have been identified when entecavir is concomitantly administered with lamivudine, adefovir dipivoxil or tenofovir disoproxil fumarate.

The interactions of entecavir with other drugs that are excreted by the kidneys or affect renal function have not been studied.

Patients should be closely monitored when entecavir is prescribed concomitantly with these drugs.

Special Instructions

In treatment with nucleoside analogues as monotherapy and in combination with antiretroviral drugs, cases of lactoacidosis and marked hepatomegaly with steatosis, sometimes leading to patient death, have been described.

Cases of exacerbation of hepatitis after discontinuation of antiviral therapy, including entecavir, have been described. Most of these cases have passed without treatment. However, severe exacerbations, including fatal ones, may develop. The causal relationship of these exacerbations to withdrawal of therapy is unknown.

After discontinuation of treatment, liver function should be monitored periodically. If necessary, antiviral therapy may be resumed. Note that when entecavir is prescribed to patients with HIV co-infection who have not previously received highly active antiretroviral therapy, there may be a risk of developing resistant strains of HIV.

Entecavir has not been studied for the treatment of HIV infection and is not recommended for such use,

Patients who have undergone liver transplantation. The safety and efficacy of entecavir in liver transplant patients is unknown. Renal function should be monitored carefully before and during treatment with entecavir in liver transplant patients receiving immunosuppressants that may affect renal function, such as cyclosporine and tacrolimus.

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

Contraindications

– age under 18 years;
– hypersensitivity to the components of the drug Baraclud.

Side effects

Gastrointestinal system disorders: rare (≥ 1/1000, < 1/100) – diarrhea, dyspepsia, nausea, vomiting.

CNS disorders: frequently (≥1/100, < 1/10) – headache, fatigue; rarely (≥1/1000, < 1/100) – insomnia, dizziness, somnolence.

Postmarketing data (frequency cannot be determined)

Allergic reactions: anaphylactoid reaction.

Dermatological reactions: alopecia, rash.

Overdose

There are limited data on cases of overdose of Baraclud in patients. No unexpected adverse reactions have occurred in healthy volunteers who received the drug in doses of up to 20 mg/day for up to 14 days or in single doses of up to 40 mg.

Treatment: In case of overdose, close medical monitoring of the patient is required.

If necessary, standard supportive therapy is given.

Pregnancy use

There have been no adequate and well-controlled studies in pregnant women.

Baraclud may be taken during pregnancy if the potential benefit from use exceeds the potential risk to the fetus.

There are no data on the penetration of entecavir into women’s milk.

Breast-feeding when using the drug is not recommended.