Product Overview
[Drug Name]
Generic Name: Entecavir Dispersible Tablets
Trade Name: Mu Chang
English Name: Entecavir Dispersible Tablets
Chinese Pinyin: EnTiKaWeiFenSanPian (Mu Chang)
[Ingredients]
The main ingredient of this product is entecavir. Chemical Name: 2-Amino-9-[(1S,3R,4S)-4-hydroxy-3-hydroxymethyl-2-methylenecyclopentyl]-1,9-dihydro-6H-purin-6-one monohydrate. Chemical Name: 2-Amino-9-[(1S,3S,4S)-4-hydroxy-3-hydroxymethyl-2-methylenecyclopentyl]-1,9-dihydro-6H-purin-6-one monohydrate. Molecular Weight: C12H15N5O3·H2O
[Properties]
This product is a white tablet.
[Indications]
This product is indicated for the treatment of chronic hepatitis B in adults with active viral replication, persistently elevated serum ALT, or active liver histological lesions.
[Dosage and Administration]
This product should be taken under the guidance of an experienced physician. Recommended Dose: Adults and adolescents aged 16 years and older should take 0.5 mg (one tablet) orally once daily. Patients who develop viremia or lamivudine-resistant mutations during lamivudine treatment should take 1 mg (two tablets) once daily. This product should be taken on an empty stomach (at least 2 hours before or after a meal). This product can be swallowed or dissolved in water for oral administration. Dispersible tablets can also be sucked orally. Renal Impairment: In patients with renal impairment, the oral clearance of entecavir decreases with decreasing creatinine clearance (see Pharmacokinetics, Special Populations). The dose should be adjusted for patients with creatinine clearance <50 mI/min (including those receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)). Hepatic Impairment: No dose adjustment is required for patients with hepatic impairment. Treatment Duration: The optimal duration of treatment with this product and its relationship to long-term treatment outcomes, such as cirrhosis and liver cancer, are currently unknown.
[Adverse Reactions]
The evaluation of adverse reactions was based on four global clinical trials: AI463014, AI463022, AI463026, and AI463027, as well as three clinical trials conducted in China (AI463012, AI463023, and AI463056). A total of 2,596 patients with chronic hepatitis B were enrolled in these seven studies. In studies comparing entecavir with lamivudine, adverse events and laboratory abnormalities were similar between entecavir and lamivudine. In studies conducted internationally, the most common adverse events for this product were headache, fatigue, dizziness, and nausea. Common adverse events in patients treated with lamivudine were headache, fatigue, and dizziness. In these four studies, 1% of entecavir-treated patients and 4% of lamivudine-treated patients withdrew from the study due to adverse events and laboratory abnormalities, respectively. Table 2 compares the differences between entecavir and lamivudine in the four clinical studies. Moderate adverse reactions and clinical adverse reactions that occurred during treatment and were at least potentially drug-related were selected as comparison indicators. a. Adverse events that were possibly, probably, related, or unclearly related to the treatment were included. b. Studies AI463022 and AI463027. cIncludes AI463026 and AI463014. AI463014 was a multinational, randomized, double-blind, phase II study conducted in patients with recurrent viremia after lamivudine treatment. These patients were either switched to three different doses of entecavir (0.1, 0.5, and 1.0 mg) once daily or continued to receive 100 mg of lamivudine once daily for 52 weeks. International Laboratory Test Abnormalities Table 3 lists the frequency of laboratory abnormalities observed in four clinical trials following treatment with entecavir and lamivudine. a During treatment, all parameters except albumin (<2.5 g/dL) deteriorated by Grade 3 or 4 compared to baseline, creatinine increased ≥0.5 mg/dL, and ALT >10 ULN and >2 times baseline levels. bStudies AI463022 and AI463027. c Includes AI463026 and AI463014. AI463014 was a multinational, randomized, double-blind, Phase II study conducted in patients with recurrent viremia after lamivudine treatment. These patients were either switched to three different doses of entecavir (0.1, 0.5, and 1.0 mg) once daily or continued on 100 mg of lamivudine once daily for 52 weeks. Grade 3 = 3+ (also 500, 1000, and 1000 g); Grade 4 = 4+, 5+ (marked, severe, and ++++, respectively; 4+ (also ++++++, and 4+ (many)). In these studies, patients receiving entecavir who experienced an ALT elevation to 10 times the upper limit of normal and twice the baseline value during treatment generally recovered after continued treatment; this elevation was preceded or accompanied by a 2-log decrease in viral load. Therefore, regular liver function testing is necessary during treatment. In clinical trials conducted in China, the most common adverse reactions to this drug were: elevated ALT, fatigue, dizziness, nausea, abdominal pain, abdominal discomfort, epigastric pain, liver discomfort, myalgia, insomnia, and urticaria. These adverse reactions were mostly mild to moderate. In studies comparing this drug to lamivudine, the incidence of adverse events was comparable to that of lamivudine. (See package insert for details.)
[Contraindications]
This drug is contraindicated in patients with hypersensitivity to entecavir or any of the ingredients in the formulation.
[Precautions]
For patients with renal insufficiency and creatinine clearance, please read the package insert carefully and use as directed by your healthcare provider.
[Use in Special Populations]
Precautions for use in children:
Safety and efficacy data for this drug in children under 16 years of age have not been established.
Precautions for Pregnancy and Lactation:
The effects of entecavir on pregnant women have not been adequately studied. This drug should only be used after a thorough balance of potential risks and benefits to the fetus. Currently, there is no data suggesting that this drug can affect mother-to-child transmission of HBV. Therefore, appropriate interventions should be implemented to prevent neonatal HBV infection. Entecavir is secreted in rat milk. However, its secretion in human milk remains unclear, so breastfeeding is not recommended for mothers taking this drug.
Precautions for Elderly Patients:
Due to insufficient clinical studies with patients aged 65 years and older, it is unclear whether elderly patients respond differently to this drug compared to younger patients. Other clinical trial reports have also failed to identify differences between elderly and younger patients. Entecavir is primarily excreted by the kidneys, and the risk of toxic reactions may be higher in patients with renal impairment. Because elderly patients often have decreased renal function, careful consideration should be given to drug dosage selection and renal function monitoring.
[Drug Interactions] Entecavir metabolism has been evaluated in vitro and in vivo. Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system. At concentrations approximately 10,000 times the human concentration, entecavir does not inhibit any of the major human CYP450 enzymes: 1A2, 2C9, 2C19, 2D6, 3A4, 2B6, and 2E1. At concentrations approximately 340 times the human concentration, entecavir does not induce the following human CYP450 enzymes: 1A2, 2C9, 2C19, 3A4, 3A5, and 2B6. Concomitant administration of drugs that inhibit or induce CYP450 metabolism has no effect on the pharmacokinetics of entecavir. Furthermore, concomitant administration of entecavir has no effect on the pharmacokinetics of known CYP substrates.
[Pharmacological Action]
Pharmacological Action: Microbiological Mechanism of Action: This product is a guanine nucleoside analog that inhibits hepatitis B virus (HBV) polymerase. It is phosphorylated to its active triphosphate, which has an intracellular half-life of 15 hours. By competing with deoxyguanosine triphosphate, the natural substrate of HBV polymerase, entecavir triphosphate inhibits all three activities of the viral polymerase (reverse transcriptase): (1) initiation of HBV polymerase; (2) formation of the reverse transcriptase negative strand of pregenomic mRNA; and (3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate has weak inhibitory effects on cellular alpha, beta, and delta DNA polymerases and mitochondrial gamma DNA polymerase, with Ki values ranging from 18 to greater than 160 muM. Antiviral activity: In human HepG2 cells transfected with wild-type HBV, the concentration required for 50% inhibition of viral DNA synthesis (EC50) of entecavir was 0.004 muM. The median EC50 of entecavir against lamivudine-resistant viral strains (rtL180M, rtM204V) was 0.026 muM (range 0.01 to 0.059 muM). Coadministration of entecavir with HIV nucleoside reverse transcriptase inhibitors (NRTIs) is unlikely to reduce the anti-HBV efficacy of entecavir or the anti-HIV efficacy of any of the other drugs in the NRTI class.
Storage: Store in a sealed container.
Specifications: 0.5 mg, calculated as C₁₂H₁₅N₅O₃
Packaging: 0.5 mg x 7 s/box
Expiry Life: 36 months
Approval Number: National Medicine Standard H20130061
Manufacturer: Shandong Lukang Pharmaceutical Co., Ltd.
