Product Overview
Generic name: Entecavir tablets
Chinese Pinyin: Entikawei Pian
Product name: Boludin
Ingredients: Entecavir
Properties: The film-coated tablets of this product appear white after removing the coating.
Indications: This product is suitable for the treatment of chronic hepatitis B in adults with active virus replication, continuous increase in serum transaminase ALT, or liver histology showing active lesions.
It is also suitable for the treatment of nucleoside-naive children with chronic HBV infection and compensatory liver disease from 2 years old to <18 years old, with evidence of active viral replication and continuous increase in serum ALT levels or moderate to severe inflammation and/or fibrosis Histological evidence. For specific usage, please refer to [Usage and Dosage].
Specification: 0.5mg*7 tablets/box
Usage and dosage: Patients should take this product under the guidance of an experienced doctor.
Recommended dosage:
Adults: take this product orally, 0.5 mg once a day. Lamivudine treatment for patients with viremia or lamivudine resistance mutations is 1.0 mg (0.5 mg two tablets) once a day.
Children: Suitable for children aged 2 to <18 years old, you can choose Entecavir oral solution or Entecavir tablets. The daily dose for patients weighing 32.6 kg or more should be 0.5 mg tablets or 10 ml (0.5 mg) oral solution. Patients weighing less than 32.6 kg should use oral solutions.
Adverse reactions: The evaluation of adverse reactions is based on 4 global clinical trials: AI463014, AI463022, AI463026, AI463027 and 3 clinical trials conducted in China (AI463012, AI463023, AI463056). In these 7 studies, a total of 2596 patients with chronic hepatitis B were enrolled. In a comparative study with lamivudine, the adverse reactions and laboratory abnormalities of entecavir and lamivudine were similar. In studies conducted abroad, the most common adverse reactions of this product are headache, fatigue, dizziness, and nausea. Common adverse reactions in patients treated with lamivudine include headache, fatigue, and dizziness. In these 4 studies, 1% of entecavir-treated patients and 4% of lamivudine-treated patients withdrew from the study due to adverse reactions and abnormal laboratory test indicators.
Contraindications: People who are allergic to entecavir or any ingredient in the preparation should be prohibited.
Note: Patients should take Entecavir under the guidance of a doctor, and inform the doctor of any new symptoms and concomitant medications. Patients should be informed that if the drug is discontinued, liver disease sometimes worsens, so the treatment should be changed under the guidance of a doctor. Entecavir treatment does not reduce the risk of HBV transmission through sexual contact or contaminated blood sources. Therefore, appropriate protective measures need to be taken.
Drug interactions: 1. In vivo and in vitro tests have evaluated the metabolism of Entecavir. Entecavir is not a substrate, inhibitor or inducer of the cytochrome P450 (CYP450) enzyme system. Entecavir does not inhibit any major human CYP450 enzymes: 1A2, 2C9, 2C19, 2D6, 3A4, 2B6 and 2E1 when the concentration reaches about 10,000 times the human body concentration. Entecavir does not induce human CYP450 enzymes: 1A2, 2C9, 2C19, 3A4, 3A5, and 2B6 when the concentration reaches about 340 times the human concentration. At the same time, taking drugs that are metabolized by inhibiting or inducing the CYP450 system has no effect on the pharmacokinetics of entecavir. Moreover, taking Entecavir at the same time has no effect on the pharmacokinetics of known CYP substrates. 2. When studying the interaction of entecavir with lamivudine, adefovir and tenofovir, it was found that the steady-state pharmacokinetics of entecavir and its interacting drugs did not change. 3. Since entecavir is mainly eliminated by the kidneys, taking entecavir may increase the blood concentration of these two drugs while taking drugs that reduce renal function or competitively secrete through active glomeruli. Taking entecavir with lamivudine, adefovir and tenofovir at the same time will not cause obvious drug interactions. The interaction of entecavir and other drugs that are cleared by the kidneys or that are known to affect kidney function have not been studied. Patients should closely monitor the occurrence of adverse reactions when taking entecavir and such drugs at the same time.
Pharmacology and Toxicology: 1. Microbiology Mechanism of action: This product is a guanosine analogue, which has an inhibitory effect on hepatitis B virus (HBV) polymerase. It can be phosphorylated into active triphosphate, the half-life of triphosphate in the cell is 15 hours. By competing with deoxyguanosine triphosphate, the natural substrate of HBV polymerase, entecavir triphosphate can inhibit all three activities of viral polymerase (reverse transcriptase): (1) HBV polymerase initiation; (2) pregenomic mRNA The formation of the negative strand of reverse transcription; (3) The synthesis of the positive strand of HBV DNA. The inhibitory constant (Ki) of entecavir triphosphate on HBV DNA polymerase is 0.0012μM. Entecavir triphosphate has a weaker inhibitory effect on cells' α, β, δ DNA polymerase and mitochondria γ DNA polymerase, with Ki values ranging from 18 to 160μM. 2. Antiviral activity In human HepG2 cells transfected with wild-type hepatitis B virus, the concentration (EC50) required for entecavir to inhibit 50% of viral DNA synthesis is 0.004μM. The median EC50 of Entecavir against lamivudine-resistant virus strains (rtL180M, rtM204V) is 0.026μ M (range 0.01 to 0.059μ M), while Entecavir is immune to type I humans grown in cell culture medium Defective virus (HIV) has no clinically relevant activity (EC50>; 10μ M). Using this product once a day or once a week can reduce the level of hepatitis virus DNA (4 to 8 log10) in North American woodchucks and ducks. A long-term study of 5 North American woodchucks showed that oral administration of 0.5 mg/kg entecavir (equivalent to a human dose of 1.0 mg) per week can keep the viral DNA of 3 of them at undetectable levels (viral DNA levels). <; 200 copies/mL, PCR method) up to 3 years away. In any animal treated with the drug for up to 3 years, no changes in HBV polymerase related to entecavir resistance were found. 3. Drug resistance In vitro studies: In cell tests, it was found that the phenotypic sensitivity of lamivudine-resistant virus strains to entecavir was reduced by 8 to 30 times. If the hepatitis B virus polymerase inherently has amino acid substitutions that are resistant to lamivudine (rtL180M and/or rtM204V/I), plus the substitution mutations at rtT184, rtS202 or rtM250, or the two mutations above On the basis of this, regardless of whether there is substitution mutation of rtI169, the phenotypic sensitivity to entecavir will decrease more (>; 70 times). 4. Clinical study: Nucleoside drug-naive patients: 81% of nucleoside-naive patients after oral entecavir 0.5mg/day for 48 weeks, the viral load reached <; 300 copies/mL.
Medications for pregnant women and lactating women: Research on the effects of entecavir on pregnant women is insufficient. This product can be used only after fully weighing the potential risks and benefits of the fetus. There is no data suggesting that this product can affect the mother-to-child transmission of HBV. Therefore, appropriate intervention measures should be taken to prevent newborns from being infected with HBV. Entecavir can be secreted from rat milk. However, it is still unclear whether there is secretion in human milk, so breastfeeding is not recommended for mothers taking this product.
Children's medication: The safety and effectiveness data of this product for children under 16 years of age have not been established.
Medication for elderly patients: As there are not enough elderly patients aged 65 and over to participate in clinical studies of this product, it is not clear what is the difference between the responses of elderly patients and young patients to this product. Other clinical trial reports also found no difference between elderly patients and young patients. Entecavir is mainly excreted by the kidneys. In patients with impaired renal function, the risk of toxicity may be higher. Because the renal function of most elderly patients has decreased, attention should be paid to the choice of drug dosage and renal function should be monitored.
Overdose: There are no reports of overdose of this product. In healthy people, after a single dose of 40 mg or multiple doses of 20 mg/day for 14 consecutive days, no increase in adverse events was observed. If an overdose occurs, the patient's toxicity indicators must be monitored, and standard supportive therapy should be performed if necessary. After a single administration of 1.0 mg of entecavir, 4 hours of hemodialysis can clear about 13% of entecavir.
Storage: sealed, stored in a dry place at 15-30℃.
Packing: aluminum foil packaging, 7 pieces/box
Validity period: 36 months
Approval number: National Medicine Zhunzi H20052237
Company Name: Sino-American Shanghai Squibb Pharmaceutical Co., Ltd.
