Entecavir Sandoz
Entecavir Sandoz: 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 Sandoz
ATX code: J05AF10
Active ingredient: entecavir (Entecavir)
Manufacturer: Lek d.d. (LEK dd) (Slovenia)
Description and photo update: 2019-08-07
Prices in pharmacies: from 2810 rubles.
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Entecavir Sandoz is an antiviral drug.
Release form and composition
The drug is produced in the form of film-coated tablets: biconvex, round, white (0.5 mg) or pink (1 mg), engraved with "108" (0.5 mg) or "109" (1 mg) with one hand, and SZ - on the other (10 pcs. in a blister, in a cardboard box 3 blisters and instructions for the use of Entecavir Sandoz).
1 tablet contains:
- active substance: entecavir monohydrate - 0.5325 or 1.065 mg, which is equivalent to entecavir in an amount of 0.5 and 1 mg, respectively;
- additional components: crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose;
- film shell: macrogol 6000, hypromellose 2910, talc, titanium dioxide; additionally for 1 mg - iron dye oxide red (E172).
Pharmacological properties
Pharmacodynamics
Entecavir is an antiviral agent that is an analogue of guanosine nucleoside and exhibits pronounced and selective activity against hepatitis B virus polymerase (HBV polymerase). As a result of the phosphorylation reaction of the active substance, active triphosphate (TF) is formed, the intracellular half-life (T ½) which is 15 hours. The concentration of TF inside the cell is directly related to the extracellular content of entecavir, while no significant accumulation of the drug occurs after the initial plateau level. By competing with the natural substrate deoxyguanosine-TF, entecavir-TF inhibits all three types of functional activity of viral polymerase: I - priming of HBV polymerase, II - reverse transcription of a negative strand from pregenomic messenger RNA (mRNA), III - synthesis of a positive HBV DNA strand.
Entecavir-TF is characterized by a weak suppression of cellular DNA polymerases α, β, and δ with an inhibition constant Ki of 18–40 μM. Also, at a high level of entecavir and entecavir-TF, undesirable reactions with respect to γ-polymerase and DNA synthesis in the mitochondria of HepG2 cells were not recorded.
Pharmacokinetics
In healthy volunteers, rapid absorption of the active substance was noted, and its maximum plasma concentration (C max) was observed after 0.5–1.5 hours. After repeated administration of entecavir at a dose varying from 0.1 to 1 mg, a dose-proportional increase in C max and the area under the pharmacokinetic curve (AUC) was recorded. Stationary concentration of the agent (C ss) was achieved after 6–10 days of oral administration once a day, while the level in blood plasma increased by an average of 2 times. In the equilibrium state, C max and the minimum plasma concentration (C min) in the blood were 4.2 and 0.3 ng / ml, respectively, when entecavir was taken at a dose of 0.5 mg; 8.2 and 0.5 ng / ml - when taken at a dose of 1 mg.
On the background of oral administration of Sandoz Entecavir in combination with food with both high and low fat content, a minimal delay in the absorption of the drug was found (1-1.5 hours - when used with food and 0.75 hours - when taken on an empty stomach), as well as decrease in AUC by 18–20% and C max by 44–46%.
According to the results of the studies, it was found that the volume of distribution (V d) of entecavir exceeds the total volume of fluid in the body, which confirms the good penetration of the drug into the tissues. The active substance binds to plasma proteins in vitro by about 13%. Entecavir is not a member of the group of inducers, inhibitors or substrates of isoenzymes of the CYP450 system. In the course of studies, after administration of labeled 14 C-entecavir to humans and rats, no acetylated or oxidized metabolites were detected, and phase II biotransformation products (sulfates and glucuronides) were detected in insignificant amounts.
Plasma level of entecavir from the moment of reaching C max decreased biexponentially, while T ½ was equal to 128-149 hours. Against the background of the use of the agent once a day, an increase in its concentration (cumulation) was noted 2 times, and the effective T ½ in this case averaged 24 hours. Entecavir is excreted mostly by the kidneys; in an equilibrium state in the urine, unchanged form is determined by 62-73% of the administered dose. Renal clearance can range from 360 to 471 ml / min and is independent of dose, indicating tubular secretion and glomerular filtration of the antiviral agent.
Indications for use
Entecavir Sandoz is recommended for the treatment of chronic hepatitis B in adults if the following factors are present:
- compensated liver damage, the presence of a viral replication phase, histological confirmation of signs of an inflammatory process in the liver and / or liver fibrosis, an increase in the level of activity of serum transaminases [aspartate aminotransferase (AST) or alanine aminotransferase (ALT)];
- decompensated liver damage.
Contraindications
Absolute:
- age up to 18 years;
- glucose-galactose malabsorption, lactase deficiency, lactose intolerance;
- lactation period;
- hypersensitivity to any component of the product.
With caution and only if the benefits exceed the possible risks, the drug can be prescribed to pregnant women, since adequate and well-controlled studies on the use of Entecavir Sandoz in patients of this group have not been conducted.
Entecavir Sandoz, instructions for use: method and dosage
Entecavir Sandoz is taken orally. Capsules should be taken on an empty stomach - the break between their intake and food intake should be at least 2 hours.
In the presence of compensated liver damage, 1 tablet of Entecavir Sandoz 0.5 mg is prescribed once a day. In the case of resistance to lamivudine, that is, with a history of hepatitis B virus viremia that does not pass during treatment with lamivudine, or with established resistance to lamivudine, entecavir is recommended to be taken once a day at a dose of 1 mg.
In the presence of uncompensated liver damage, Entecavir Sandoz is prescribed 1 time per day at a dose of 1 mg.
Since with a decrease in creatinine clearance (CC), the clearance of the drug decreases, it is necessary to adjust the doses of entecavir in patients with renal insufficiency and CC <50 ml / min, including in patients undergoing hemodialysis treatment and during long-term outpatient peritoneal dialysis. …
The recommended dosage regimen of Entecavir Sandoz, depending on the CC (doses are indicated for the following groups of patients - who have not previously taken nucleoside preparations / are resistant to lamivudine or with decompensated liver damage):
- CC ≥ 50 ml / min: once a day, 0.5 / 1 mg;
- CC - 30–49 ml / min: every 48 hours, 0.5 / 1 mg;
- CC - 10-29 ml / min: every 72 hours, 0.5 / 1 mg;
- CC <10, hemodialysis * or outpatient peritoneal dialysis: every 5-7 days, 0.5 / 1 mg.
* It is recommended to take Entecavir Sandoz after the end of the hemodialysis session.
Side effects
- immune system: rarely (from ≥ 1/10 000 to <1/1000) - anaphylactoid reactions;
- nervous system: often (from ≥ 1/100 to <1/10) - drowsiness, dizziness, headache;
- mental disorders: often - insomnia;
- skin and subcutaneous tissues: infrequently (from ≥ 1/1000 to <1/100) - rash, alopecia;
- liver and biliary tract: often - increased activity of hepatic transaminases;
- digestive system: often - nausea, diarrhea, vomiting, dyspepsia;
- general disorders: often - fatigue.
Cases of lactic acidosis were also recorded, mainly associated with severe liver failure or other serious diseases, or associated with the use of other drugs.
With a long course of treatment (up to 96 weeks), no significant changes were found in the safety profile of entecavir.
Additionally, against the background of decompensated liver damage, the following adverse reactions were observed:
- often: platelet count less than 50,000 / mm³; albumin concentration below 2.5 g / dl; a decrease in the level of bicarbonate in the blood, an increase in the activity of ALT and an increase in the level of bilirubin by more than 2 times compared with the upper limit of the norm (UHN), an increase in the activity of lipase by more than 3 times when compared with the norm;
- rarely: renal failure.
Overdose
There are very few reports of entecavir overdose. When healthy volunteers received the drug in daily doses up to 20 mg in a course of up to 14 days and when taking single doses not exceeding 40 mg, no unforeseen undesirable effects were recorded.
If an overdose is suspected, the patient should be monitored to identify possible signs of toxicity and, if necessary, carry out standard supportive treatment.
special instructions
With the use of entecavir and other nucleoside analogs in monotherapy or in combination with antiretroviral drugs, cases of lactic acidosis (without hypoxemia) have been reported, usually associated with hepatic steatosis and severe hepatomegaly, sometimes leading to death. Symptoms of this complication may include the following disorders: sudden weight loss, vomiting, nausea, general fatigue, abdominal pain, muscle weakness, rapid breathing, shortness of breath. In severe cases, sometimes fatal, liver failure / hepatic steatosis, pancreatitis, renal failure, and increased serum lactate may occur.
Treatment with Entecavir Sandoz should be abandoned if progressive hepatomegaly, symptoms of metabolic acidosis / lactic acidosis, or a sudden increase in aminotransferase activity occur. Risk factors for the development of lactic acidosis include obesity, female sex, hepatomegaly, and prolonged therapy with nucleoside analogues. When making a differential diagnosis of an increase in the content of aminotransferases, possible as a result of a response to the use of the drug or due to the likelihood of lactic acidosis, the doctor should make sure that changes in ALT levels are associated with an improvement in other laboratory markers of the course of chronic hepatitis B.
During the treatment period, spontaneous exacerbations of chronic hepatitis B, characterized by a temporary increase in serum ALT activity, are relatively common. In some patients, after the initial period of therapy, an increase in serum ALT levels and a simultaneous decrease in HBV DNA indicators is possible. Such an increase in ALT activity against the background of compensated liver damage in the overwhelming majority did not lead to an increase in the concentration of bilirubin or decompensation of liver function. In patients with cirrhosis of the liver, after an exacerbation of hepatitis, the threat of decompensation of liver function may be aggravated, as a result of which they should be carefully monitored during the period of therapy.
There are descriptions of cases of exacerbation of hepatitis after the cessation of antiviral therapy, mainly associated with an increase in HBV DNA and passing on their own. However, there were also cases of severe exacerbations, including fatal ones. With the cancellation of entecavir, the causal relationship of these complications has not been established. It is necessary to carry out regular monitoring of liver activity, clinical symptoms and laboratory parameters for at least six months after the termination of antiviral therapy. If necessary, hepatitis treatment can be resumed.
It is required to take into account that the use of entecavir by patients with co-infection of the human immunodeficiency virus (HIV) who do not receive antiretroviral therapy increases the threat of emergence of resistant strains of HIV. The use of Entecavir Sandoz for the treatment of HIV infection has not been studied, therefore it is not recommended to use the drug in such cases.
There is no information on the effectiveness of drug therapy in patients with combined hepatitis B / hepatitis C / hepatitis D infections.
An increase in the risk of severe adverse reactions from the liver was noted in decompensated liver damage (regardless of the cause), especially class C according to the Child-Pugh classification. In addition, in patients with this pathology, the risk of lactic acidosis and such a phenomenon as hepatorenal syndrome may be aggravated. In this regard, in patients of this group, it is necessary to carefully monitor the results of the corresponding laboratory tests (lactic acid content, serum creatinine level, liver enzyme activity), clinical signs of lactic acidosis and impaired renal function.
Patients with lamivudine-resistant HBV have a higher risk of subsequent entecavir resistance than those who do not have lamivudine resistance. Therefore, if patients are resistant to lamivudine, the virologic response should be monitored more frequently and the necessary tests performed to establish entecavir resistance. After 24 weeks of taking the latter, the therapy regimen may be changed in patients with a suboptimal virological response. At the beginning of the course of treatment in patients with documented resistance to lamivudine, combination therapy of Entecavir Sandoz with another antiviral agent (to which there is no cross-resistance) is preferable to drug monotherapy.
It should be borne in mind that treatment with Sandoz with Entecavir does not reduce the risk of hepatitis B transmission, so that appropriate precautions should not be neglected.
Influence on the ability to drive vehicles and complex mechanisms
The effect of Entecavir Sandoz on the ability to control complex moving mechanisms has not been studied. However, the possible appearance of fatigue, drowsiness and dizziness during the period of therapy can negatively affect the ability to drive a car and other equipment.
Application during pregnancy and lactation
Well-controlled and adequate studies have not been conducted for the treatment of pregnant women with entecavir. Entecavir Sandoz should be used during pregnancy only if the expected benefit of therapy to the mother significantly outweighs the potential threat to the health of the fetus. There is no data on the effect of the drug on mother-to-child transmission of HBV, and therefore it is necessary to take the necessary measures to prevent possible neonatal HBV infection.
When using an antiviral agent during lactation, the child should be transferred to artificial feeding, since there is no reliable information about the possible excretion of entecavir in breast milk.
Women of childbearing age should use reliable methods of contraception during therapy due to the possible risk to the developing fetus.
Pediatric use
Entecavir Sandoz is not indicated for patients under 18 years of age.
With impaired renal function
In the presence of functional disorders of the kidneys, it is necessary to adjust the dosage regimen taking into account the CC values. During the period of therapy, it is necessary to monitor the virological response.
For violations of liver function
If you have hepatic impairment, you do not need to change the dose of Entecavir Sandoz.
The efficacy and safety of using the drug in patients who underwent liver transplantation have not been studied. Patients in this risk group before and during therapy require careful monitoring of renal activity. Such monitoring is also necessary when patients receive immunosuppressive drugs (including tacrolimus and cyclosporine), which may affect renal function.
Use in the elderly
Elderly patients do not require individual selection of entecavir doses.
Drug interactions
- drugs that reduce renal function or compete with entecavir at the level of tubular secretion: there may be an increase in serum concentration in the blood of these agents or entecavir, since the latter is excreted mainly by the kidneys;
- adefovir, lamivudine, tenofovir: no significant pharmacokinetic interactions were observed;
- other drugs that are eliminated by the kidneys or that affect renal function: interaction with entecavir has not been studied, therefore, medical monitoring of the patient's condition should be established against the background of such combination therapy.
Analogs
The analogues of Entecavir Sandoz are: Elgravir, Baraklud, Entecavir, etc.
Terms and conditions of storage
Store out of the reach of children at a temperature not exceeding 30 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Entecavir Sandoz
On medical websites, reviews of Entecavir Sandoz are very rare, since the drug was registered in the Russian Federation only at the beginning of 2018. Basically, the drug, as well as its analogues, received a positive assessment - patients note the effectiveness of the drug in combating the consequences of hepatitis B and its relatively good tolerance. The disadvantages of an antiviral agent include the possible occurrence of adverse reactions.
The price of Entecavir Sandoz in pharmacies
The average price for Entecavir Sandoz 0.5 mg is 3300 rubles. for a pack of 30 tablets, for Entecavir Sandoz 1 mg - 6200 rubles. per pack of 30 tablets.
Entecavir Sandoz: 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 Sandoz tab. cover p / o 0.5 mg No. 30 3856 RUB Buy |
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Entecavir Sandoz 1 mg film-coated tablets 30 pcs. RUB 6159 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!
