Entecavir
Entecavir: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Entecavir
ATX code: J05AF10
Active ingredient: entecavir (Entecavir)
Producer: Pharmstandard-Tomskkhimfarm OJSC (Russia)
Description and photo update: 28.11.2018
Prices in pharmacies: from 2810 rubles.
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Entecavir is an antiviral agent.
Release form and composition
Dosage form - tablets: round, biconvex, white / almost white (0.5 mg each) or pink (1 mg) color; the cross section shows an almost white / white core (10 pcs. in blisters, 3 packs in a cardboard box and instructions for use of Entecavir).
Composition of 1 tablet:
- active substance: entecavir monohydrate - 0.5 or 1 mg (in terms of entecavir);
- auxiliary components: crospovidone type B, povidone K-30, microcrystalline cellulose, magnesium stearate, lactose monohydrate;
- the composition of the film shell: 0.5 mg tablets - macrogol, talc, polyvinyl alcohol, titanium dioxide; 1 mg tablets - macrogol, talc, polyvinyl alcohol, titanium dioxide, iron dye red oxide (E 172), iron dye yellow oxide (E 172), iron dye black oxide (E 172).
Pharmacological properties
Pharmacodynamics
The active ingredient of the drug is entecavir, an analogue of guanosine nucleoside, which has a pronounced and selective effect against HBV polymerase (hepatitis B virus polymerase). The substance undergoes a phosphorylation process, as a result of which active triphosphate (TF) is formed with an intracellular half-life (T 1/2) of 12 hours. The intracellular TF concentration is directly related to the extracellular concentration of entecavir, while after reaching the initial plateau level, the drug does not accumulate.
By competing with the natural substrate (deoxyguanosine-TF), entecavir-TF suppresses all three functional activities of viral polymerase: 1 - priming of HBV polymerase, 2 - reverse transcription of a negative strand from pregenomic messenger ribonucleic acid (mRNA), 3 - synthesis of a positive HBV DNA strand …
Entecavir-TF weakly inhibits cellular DNA polymerases α-, β-, δ- with an inhibition constant Ki of 18–40 μM. At high concentrations of the substance, no adverse reactions were observed in relation to γ-polymerase and DNA synthesis in the mitochondria of HepG2 cells.
The antiviral activity of entecavir on HBV DNA synthesis was evaluated in wild-type HBV HepG2 cells. The concentration of the drug required to suppress 50% of viruses (EC 50) was 0.004 μM. Median EC 50 entecavir against lamivudine-resistant strains of HBV (rtL180M and rtM204V) was 0.026.mu. M (.mu. M 0,010-0,059).
In a panel of laboratory and clinical HIV-1 isolates, analysis of entecavir antiviral activity showed an EC 50 range of 0.026 to> 10 μM.
In studies of combinations of entecavir with nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine, abacavir, zidovudine, stavudine or didanosine and NRTI tenofovir, carried out on cell cultures, no antagonistic effect was found with respect to the antiviral activity of the drug against HBV.
When studying the antiviral action of entecavir against HIV (human immunodeficiency virus) with the same six NRTIs, no antagonistic effect was also found.
Compared to wild-type HBV, lamivudine-resistant strains with the rtM204V and rtL180M mutations in reverse transcriptase are 8 times less sensitive to entecavir. The rtT 184, rtS202 and rtM250 mutations responsible for entecavir resistance do not significantly affect sensitivity to it, provided there are no mutations that cause lamivudine resistance.
Pharmacokinetics
In healthy volunteers, after oral administration, the drug is absorbed quickly. The maximum plasma concentration (Cmax) reaches within 0.5-1.5 hours.
With repeated use in the dose range of 0.1–1 mg, a proportional increase in Cmax and AUC (area under the concentration-time curve) was noted. Css (equilibrium concentration) is achieved within 6-10 days when taking Entecavir 1 time per day, while the plasma concentration increases by about 2 times. In the equilibrium state, when using the drug at a dose of 0.5 mg, the maximum and minimum concentrations are 4.2 and 0.3 ng / ml, respectively, for a dose of 1 mg these indicators are 8.2 and 0.5 ng / ml. With the simultaneous use of fatty foods, there is a slight delay in absorption (1-1.5 hours compared to 0.75 hours in the case of taking the drug on an empty stomach), a decrease in AUC by 18-20% and Cmax by 44-46%.
The estimated volume of distribution of entecavir in studies exceeded the total volume of water in the body. These data indicate good penetration of the substance into tissues. In vitro, the connection with blood plasma proteins is about 13%.
Entecavir is not an inducer, inhibitor, or substrate of CYP450 enzymes. With the introduction of labeled 14 C-entecavir, acetylated and oxidized metabolites are not detected, phase II metabolites (sulfates and glucuronides) are determined in small amounts.
After the moment Cmax is reached, the plasma level of entecavir decreases biexponentially, T1 / 2 in this case is 128-149 hours.
With a single dose of the drug once a day, entecavir accumulates (a 2-fold increase in concentration), the effective T 1/2 in this case reaches 24 hours.
The substance is excreted mainly by the kidneys. In an equilibrium state, 62–73% of unchanged entecavir is determined in urine. Renal clearance does not depend on the dose, fluctuates in the range of 360–471 ml / min, which indicates tubular secretion and glomerular filtration of the drug.
Indications for use
Entecavir is used to treat chronic hepatitis B in adults with the following co-factors:
- decompensated liver damage;
- compensated liver damage and the presence of viral replication, histological signs of inflammation in the liver, increased levels of serum transaminase [alanine aminotransferase (ALT) or aspartate aminotransferase (ACT)] activity and / or fibrosis.
Contraindications
- hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- age up to 18 years;
- hypersensitivity to any component of the drug.
Entecavir is prescribed with caution in case of impaired renal function.
Entecavir, instructions for use: method and dosage
Entecavir tablets should be taken orally, on an empty stomach (the interval between doses of the drug and food should be at least 2 hours).
With compensated liver damage, the dose of Entecavir is 0.5 mg once a day.
In the case of resistance to lamivudine (i.e., with anamnestic evidence of hepatitis B virus viremia persisting with lamivudine use, as well as with confirmed resistance to lamivudine), the recommended dose is 1 mg once a day.
With uncompensated liver damage, 1 mg is prescribed once a day.
Prescribing Entecavir to patients with renal insufficiency
With a reduced creatinine clearance (CC), the clearance of entecavir decreases, and therefore a dose adjustment of the drug is required, including during hemodialysis and long-term outpatient peritoneal dialysis.
Recommended dosage regimens depending on creatinine clearance for patients who have not previously received nucleoside drugs, as well as for lamivudine-resistant or patients with decompensated liver damage:
- CC ≥ 50 ml / min: 0.5 mg once a day; 1 mg once a day;
- CC 30–49 ml / min: 0.5 mg 1 time in 2 days; 1 mg once every 2 days;
- CC 10-29 ml / min: 0.5 mg 1 time in 3 days; 1 mg once every 3 days;
- hemodialysis * or outpatient peritoneal dialysis: 0.5 mg every 5–7 days; 1 mg every 5-7 days.
* Entecavir is taken after a hemodialysis session.
Side effects
- from the side of the immune system: rarely (from ≥ 1/10000 to <1/1000) - anaphylactoid reaction;
- on the part of the skin and subcutaneous tissue: infrequently (from ≥ 1/1000 to <1/100) - rash, alopecia;
- from the digestive system: often (from ≥ 1/100 to <1/10) - diarrhea, nausea, vomiting, dyspepsia;
- from the liver: often - increased activity of transaminases;
- general disorders: often - weakness;
- mental disorders: often - insomnia;
- from the central nervous system: often - drowsiness, headache, dizziness;
- from the metabolic side: lactic acidosis (abdominal pain, nausea, vomiting, sudden weight loss, rapid breathing, shortness of breath, general fatigue, muscle weakness), often associated with uncompensated liver damage, other serious diseases or concomitant use of any medications funds.
In patients with decompensated liver damage, in addition, the following disorders are possible: often - platelet concentration below 50,000 / mm 3, albumin concentration less than 2.5 g / dL, increase in ALT activity and bilirubin concentration by more than 2 times compared to the upper limit norms, an increase in lipase activity by more than 3 times compared with the norm, a decrease in the concentration of bicarbonate in the blood; rarely, renal failure.
With prolonged therapy (up to 96 weeks), no changes were noted in the safety profile of entecavir.
Overdose
There are isolated reports of overdose cases. In healthy volunteers who received doses up to 40 mg once or up to 20 mg / day for 14 days, no unexpected side effects were reported.
In case of overdose, careful monitoring of the patient's condition is required, if necessary, standard maintenance therapy is required.
special instructions
The physician should warn patients that taking Entecavir does not reduce the risk of hepatitis B transmission, so appropriate precautions should be taken.
Each 0.5 mg Entecavir tablet contains 69.97 mg of lactose monohydrate, 1 mg - 139.94 mg.
Lactic acidosis and severe hepatomegaly with steatosis
Nucleoside analogs can cause lactic acidosis associated with steatosis and severe hepatomegaly, sometimes resulting in patient death. When treating with the drug, this risk should be taken into account. Symptoms that may indicate the development of lactic acidosis: muscle weakness, general fatigue, rapid breathing, shortness of breath, sudden weight loss, abdominal pain, nausea, vomiting. In severe cases, a concomitant increase in serum lactate levels, the development of pancreatitis, liver failure / hepatic steatosis, and renal failure are possible. Additional risk factors: hepatomegaly, long-term use of nucleoside analogs, obesity, female sex.
Therapy with the drug should be urgently discontinued in case of a rapid increase in the level of aminotransferases, the development of progressive hepatomegaly, the appearance of symptoms of lactic acidosis described above.
When differential diagnosis of elevated aminotransferase levels in response to entecavir therapy or as a result of the potential development of lactic acidosis, the physician should ensure that an increase in ALT is associated with an improvement in other laboratory parameters of chronic hepatitis B virus activity.
Considering the above information, Entecavir should be used with caution in hepatitis, hepatomegaly and other known risk factors for liver disease. During the treatment period, more careful monitoring of the patient's condition is required.
Decompensated liver damage
With decompensated liver disease (Child-Pugh class C), there is a high risk of serious liver side effects, regardless of whether entecavir is used or not. In such patients, however, there is a risk of developing lactic acidosis and hepatorenal syndrome.
In this connection, careful monitoring of the patient's condition is required for the appearance of clinical signs of impaired renal function and the development of lactic acidosis. It is recommended to carry out appropriate laboratory tests, including the determination of the concentration of creatinine in the blood serum, the concentration of lactic acid in the blood and the activity of liver enzymes.
Exacerbation of hepatitis
After the end of antiviral therapy, an exacerbation of hepatitis is possible. In general, additional treatment is not required, however, the risk of developing severe exacerbations, up to and including death, should be considered. A causal relationship with discontinuation of entecavir has not been established.
With compensated liver disease, ALT activity may increase. When decompensated, there is a high risk of exacerbation of hepatitis.
In patients, it is necessary to regularly monitor hepatic function for at least 6 months after discontinuation of antiviral therapy. If necessary, treatment should be resumed.
Conditions after liver transplantation
In patients after liver transplantation, the efficacy and safety of entecavir have not been established. Such patients need to ensure careful monitoring of renal function before and during the appointment of Entecavir. This monitoring is especially important in the case of concomitant use of immunosuppressive drugs (for example, tacrolimus or cyclosporine), which can affect renal function.
Lamivudine resistance
Patients with hepatitis B virus resistance mutations to lamivudine are at increased risk of developing entecavir resistance. For this reason, viral load monitoring should be carried out frequently in lamivudine resistance, and if necessary, appropriate testing should be done to identify resistance mutations. In patients with suboptimal virological response, after 24 weeks of using Entecavir, a change in the therapeutic regimen is possible.
For patients with known resistance to lamivudine at the beginning of therapy, it is considered more preferable to prescribe entecavir in combination with another antiviral drug to which there is no cross-resistance.
Combined hepatitis B / hepatitis C / hepatitis D infection
There is no information on the effectiveness of using the drug in this category of patients.
Combined hepatitis B / HIV infection
Patients with HIV co-infection who are not receiving antiretroviral therapy are at increased risk of developing resistant strains of HIV.
The effectiveness of entecavir has not been studied. It is not recommended to use this antiviral drug in such cases.
Influence on the ability to drive vehicles and complex mechanisms
Special studies on the effect of entecavir on the psychomotor and physical abilities of a person have not been conducted.
Application during pregnancy and lactation
Controlled studies on the use of entecavir in pregnant women have not been conducted. Animal studies have shown that the drug has a toxic effect on reproductive function in the case of high doses. During pregnancy, Entecavir should only be used if there is a clear benefit in relation to the risks.
There is no clinical data on the penetration of the substance into breast milk, excretion was noted in the course of studies. In this regard, you should not breastfeed during therapy, including to avoid postnatal transmission of HBV.
Women of childbearing age are advised to use reliable methods of contraception during treatment.
Pediatric use
Entecavir is not used to treat patients under the age of 18.
With impaired renal function
In renal failure, a dose reduction of Entecavir is required depending on creatinine clearance. Treatment is carried out under the control of the virological response.
For violations of liver function
In liver failure, the dose of the drug is not adjusted.
Use in the elderly
There is no need to adjust the dose of Entecavir in elderly patients.
Drug interactions
There were no significant drug interactions with the simultaneous use of adefovir, lamivudine, tenofovir with Entecavir.
When combined with drugs that reduce renal function or compete at the level of tubular secretion, it is possible to increase the concentration of entecavir in serum or these drugs.
Reactions of entecavir with other drugs that affect renal function or are excreted by the kidneys have not been studied. Therefore, the patient must be under close medical supervision when using such combinations.
Analogs
Entecavir analogs are Baraklud, Elgravir, Entecavir Sandoz, etc.
Terms and conditions of storage
Store in its original packaging at temperatures up to 25 ° C out of reach of children, protected from light.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Entecavir
Reviews of Entecavir are positive: patients note the high efficacy of the antiviral agent for hepatitis B and its good tolerance. Some reports indicate the development of side effects.
The price of Entecavir in pharmacies
The price of Entecavir is currently unknown.
The approximate cost of its popular analogue Baraklyud for 30 tablets per pack is: 0.5 mg tablets - 7066 rubles, 1 mg tablets - 10,069 rubles.
Entecavir: prices in online pharmacies
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Drug name Price Pharmacy |
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Entecavir Sandoz 0.5 mg film-coated tablets 30 pcs. 2810 RUB Buy |
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Entecavir shtada tablets p.p. 0.5 mg 30pcs RUB 5360 Buy |
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Entecavir Sandoz 1 mg film-coated tablets 30 pcs. RUB 6159 Buy |
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Entecavir shtada tablets p.p. 1mg 30pcs 7584 RUB Buy |
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Entecavir Sandoz tablets p.o. 1,0mg 30 pcs. RUB 8617 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
