Adefovir Dipivoxil Tablets

Chronic toxicity: In animal experiments, tubular nephropathy characterized by histological changes and/or increased urea nitrogen and serum creatinine is the main dose-limiting toxic reaction of adefovir dipivoxil. The exposure of nephrotoxicity observed in animal experiments is at least 3-10 times the exposure at the recommended human therapeutic dose (10 mg/day). Genotoxicity: In in vitro mouse lymphocytoma cell experiments (with or without metabolic activation), adefovir has a mutagenic effect. Adefovir can induce chromosomal aberrations in in vitro experiments of human peripheral blood lymphocytes without metabolic activation. In the in vivo mouse micronucleus experiment, adefovir has no chromosomal clastogen effect; in the Ames bacterial reverse mutation experiment using Salmonella typhimurium and Escherichia coli strains (with or without metabolic activation), adefovir has no mutagenicity. Reproductive toxicity: No effect on rat fertility was observed at an exposure of approximately 19 times the exposure at the human therapeutic dose. Oral administration of adefovir dipivoxil to rats and rabbits (exposures were approximately 23 times and 40 times the human therapeutic dose of 10 mg/day, respectively) did not result in embryotoxicity or teratogenicity. Adefovir was administered intravenously to pregnant rats, and at doses that could produce significant maternal toxicity (equivalent to 38 times the exposure at the recommended therapeutic dose for humans), the incidence of embryotoxicity and fetal malformations (systemic edema, sunken eyelids, umbilical hernia, and tail kinking) increased. No adverse effects were observed at intravenous doses equivalent to 12 times the human exposure. Carcinogenicity: In long-term carcinogenicity studies in mice and rats, mice and rats were orally administered adefovir dipivoxil at doses equivalent to 10 times and 4 times the exposure of the human therapeutic dose (10 mg/day), respectively, and no carcinogenic effects were observed. Pharmacological action: Mechanism of action Adefovir is an acyclic phosphorylated nucleoside analog of adenosine monophosphate. It is phosphorylated to an active metabolite, adefovir diphosphate, under the action of cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) in the following two ways: one is to compete with the natural substrate deoxyadenosine triphosphate, and the other is to cause DNA chain extension termination after integration into viral DNA. The inhibition constant (Ki) of adefovir diphosphate on HBV DNA polymerase is 0.1mu;M. However, the inhibitory effect on human DNA polymerase alpha; and gamma; is weaker, with Ki values of 1.18mu;M and 0.97mu;M, respectively. Antiviral activity: The concentration of adefovir that inhibits 50% viral DNA replication in vitro (IC50) determined by human hepatoma cell lines transfected with HBV is 0.2~2.5mu;M. Adefovir combined with lamivudine exhibits additional anti-HBV activity in vitro. Drug resistance: Long-term (96-144 weeks) drug resistance genotype analysis was performed on patients who still had detectable serum HBV DNA after receiving adefovir treatment, and it was determined that rtN236T and rtA181V mutations were associated with adefovir resistance. In vitro studies found that the rtN236T mutation caused HBV to be 4-14 times less sensitive to adefovir, and the serum HBVDNA levels of the six patients with this mutation rebounded. The rtA181V mutation caused its in vitro sensitivity to adefovir to be reduced by 2.5-3 times. Among the three patients with this mutation, the serum HBVDNA levels of two patients rebounded. The incidence of mutations associated with adefovir resistance was 0% (0/629) in 0-48 weeks, 2% (6/293) in 49-96 weeks, and 1.8% (3/163) in 97-144 weeks, with a cumulative probability of 3.9% in 3 years. Cross-resistance: Recombinant HBV variants containing lamivudine resistance-related mutations (rtL_180M, rtM204l, rtM204V, rtL180MrtM204V, rtV173L) on the HBV DNA polymerase gene are sensitive to adefovir in vitro. In patients with lamivudine-resistant null HBV, adefovir also showed anti-HBV effects, with a median decrease of 4.3log10 copies/ml in serum HBV DNA. HBV variants containing DNA polymerase mutations (rtT128N and rtR153Q or rtW153Q, which are associated with hepatitis B immunoglobulin resistance) are sensitive to adefovir in vitro. The HBV strain expressing the rtN236T variant associated with adefovir resistance is 2-3 times less sensitive to lamivudine in vitro, but is still sensitive to lamivudine in vivo. The HBV strain expressing the adefovir resistance-associated rtA181V variant was 3-fold less sensitive to lamivudine in vitro.

The main ingredient of this product is adefovir dipivoxil. Chemical name: 9-[2-[di(pivaloyloxy)methyl]phosphinyl]methoxy]ethyl]adenine Molecular weight: C20H32N5O8P

This product is white or off-white tablets.

This product is suitable for the treatment of adult patients with chronic hepatitis B with active replication of hepatitis B virus and compensated liver function with persistent elevation of serum amino acid transferase.

Patients must use this product under the guidance of a physician who has experience in treating chronic hepatitis B. Dosage: For adults (18-65 years old), the recommended dose is 1 tablet once a day, orally before or after meals. Patients should regularly monitor hepatitis B biochemical indicators, virological indicators and serum markers, at least once every 6 months. (For other details, see the instructions)

Common adverse reactions in foreign clinical studies include weakness, headache, abdominal pain, nausea, (gastrointestinal) flatulence, diarrhea and indigestion. In domestic clinical studies, the adverse reactions observed include: chest tightness, headache, dry eyes, nausea, vomiting, abdominal distension, upper abdominal pain, conscious hair loss, liver nodules, irregular menstruation, leukopenia, thrombocytopenia, increased blood urea nitrogen, increased blood creatinine, increased blood sodium concentration, abnormal liver function, abnormal blood amylase, increased SB, increased ALP, increased CPK, increased TBil, prolonged PT, abnormal transpeptidase, and abnormal blood sugar. Post-marketing data: In addition to the adverse reactions reported in clinical trials, the following possible adverse reactions have been reported after Adefovir dipivoxil was launched. Since such adverse events are voluntarily reported and come from an unknown number of people, their frequency of occurrence has not been evaluated. Metabolic and nutritional abnormalities: hypophosphatemia Muscle and connective tissue abnormalities: myopathy, osteomalacia (both related to proximal renal tubule disease) Digestive system abnormalities: pancreatitis Kidney and urinary system abnormalities: renal failure, proximal renal tubule disease, Fanconi syndrome.

It is contraindicated in patients with known hypersensitivity to adefovir, adefovir dipivoxil, or the human and excipients in adefovir dipivoxil tablets.

Precautions for children: The efficacy and safety of adefovir dipivoxil in patients under 18 years of age have not been determined. This product should not be used in children and adolescents. Precautions for pregnancy and lactation: There is insufficient data on the use of adefovir dipivoxil in pregnant women. Adefovir dipivoxil can only be considered for use during pregnancy when the potential benefits are definitely greater than the risks to the fetus. Because the risk to the developing human embryo is not yet clear, it is recommended that women of childbearing age treated with adefovir dipivoxil take effective contraceptive measures. The effects of this product on pregnant women and mother-to-child transmission of HBV have not been studied. Therefore, infants should be immunized according to the standard recommended regimen to prevent neonatal HBV infection. Because the potential risk to the developing human embryo is not yet clear, it is recommended that women of childbearing age treated with adefovir dipivoxil take effective contraceptive measures. It is not yet known whether adefovir dipivoxil will be secreted into human milk, and lactating women should avoid breastfeeding when using this product. Precautions for the elderly: The efficacy and safety of adefovir dipivoxil in elderly patients over 65 years old have not yet been determined.

Adefovir dipivoxil is rapidly converted to adefovir in the body. At concentrations significantly higher than those observed in vivo (>4000 times), adefovir has no inhibitory effect on any of the following common human CYP450 enzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Adefovir is not a substrate for these enzymes. However, it is not clear whether adefovir induces CYP450 enzymes. Based on the results of in vitro experiments and the renal elimination pathway of adefovir, the possibility of adefovir as an inhibitor or substrate, mediated by CYP450, and interacting with other drugs is very small. Adefovir is excreted through the kidneys by glomerular filtration and active tubular secretion. 10mg adefovir dipivoxil and other drugs secreted by the renal tubules

Store in a cool, dry place.

10mg

18 months

Lesheng Pharmaceutical Shijiazhuang Co., Ltd.

• Founded in:

  2002-12-10

• Address:

  No. 198, Xiangjiang Road, Shijiazhuang High-tech Zone

• Tax NO.:

  9113010180441898XY

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  830,000 yuan

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