Product Overview
[Drug Name]
Adefovir Dipivoxil Tablets
[English Name]
Adefovir Dipivoxil Tablets
[Approval Number]
National Medicine Standard No. H20163410
[Manufacturer]
Anhui Anke Hengyi Pharmaceutical Co., Ltd.
[Indications]
Indicated for the treatment of adult patients with chronic hepatitis B who have active hepatitis B virus replication and persistently elevated serum aminotransferase levels and compensated liver function.
[Dosage and Administration]
This product must be used under the guidance of a physician experienced in treating chronic hepatitis B. For adults (18 to 65 years), the recommended dose is one 10 mg tablet once daily, taken orally before or after meals. The optimal duration of treatment has not been determined. Do not exceed the recommended dose. Patients should regularly monitor hepatitis B biochemical, virological, and serum markers at least every six months.
[Side effects/adverse reactions]
Common adverse reactions in foreign clinical studies are weakness, headache, abdominal pain, nausea, (gastrointestinal) flatulence, diarrhea and indigestion. Adverse reactions in domestic clinical studies are leukopenia (mild), diarrhea (mild) and alopecia (moderate). One serious adverse event occurred in the clinical study, which was a case of acute myeloid leukemia M3 type after 29 weeks of treatment with this product. The researchers judged that it was not related to this product.
[Contraindications]
This product is contraindicated for patients who have been confirmed to be allergic to any component of this product.
[Ingredients]
Adefovir dipivoxil
[Properties]
This product is a white tablet.
[Precautions]
(1) Patients who stop hepatitis B treatment will experience acute exacerbation of hepatitis, including stopping the use of adefovir dipivoxil. Therefore, patients who stop hepatitis B treatment should closely monitor liver function and, if necessary, resume anti-hepatitis B treatment.
(2) For patients with renal dysfunction or potential risk of renal dysfunction, chronic treatment with adefovir dipivoxil can cause nephrotoxicity. These patients should have their renal function closely monitored and their dose adjusted appropriately.
(3) All patients should be tested for human immunodeficiency virus (HIV) antibodies before treatment with adefovir dipivoxil. The use of anti-hepatitis B drugs, such as adefovir dipivoxil, can have an effect on unknown or untreated HIV carried by patients with chronic hepatitis B, and HIV resistance may develop.
(4) Nucleoside analogs used alone or in combination with other antiretroviral drugs can cause lactic acidosis and severe hepatomegaly with steatosis, including fatal events.
(5) Because the risk to developing human embryos is not yet clear, it is recommended that women of childbearing age treated with adefovir dipivoxil take effective contraceptive measures.
[Pharmacological Action]
Mechanism of Action: Adefovir is an acyclic nucleoside analog of adenosine monophosphate that is phosphorylated to its active metabolite, adefovir diphosphate, by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) through two mechanisms: competition with the natural substrate deoxyadenosine triphosphate (DATP) and termination of DNA chain elongation following integration into viral DNA. Adefovir diphosphate has an inhibition constant (KI) of 0.1 μM for HBV DNA polymerase, but its inhibitory activity against human DNA polymerases α and γ is weaker, with KI values of 1.18 μM and 0.97 μM, respectively. Antiviral activity: In human hepatoma cell lines transfected with HBV, the concentration of adefovir that inhibits viral DNA replication by 50% (IC50) ranges from 0.2 to 2.5 μM. Drug resistance: Long-term drug resistance analysis (96 to 144 weeks) in patients with detectable serum HBV DNA despite adefovir dipivoxil treatment identified the RTN236T and RTAL81V mutations as associated with adefovir resistance. In vitro studies have found that the RTN236T mutation reduces HBV susceptibility to adefovir by 4-14 fold, with serum HBV DNA rebound observed in 6/6 patients harboring this mutation. The RTA181V mutation reduces HBV susceptibility to adefovir by 2.5-3 fold, with rebound observed in 2/3 patients harboring this mutation. The incidence of mutations associated with adefovir resistance was 0% (0/629) from 0 to 48 weeks, 2% (6/293) from 49 to 96 weeks, and 1.8% (3/163) from 97 to 144 weeks, with a cumulative incidence of 3.9% over 3 years. Cross-resistance: Recombinant HBV variants harboring lamivudine-resistance-associated mutations in the HBV DNA polymerase gene (RTL180M, RTM204I, RTM204V, RTL180M+RTM204V, RTV173L) were susceptible to adefovir in vitro. Adefovir dipivoxil also demonstrated anti-HBV activity in patients harboring lamivudine-resistant HBV variants, with a median decrease in serum HBV DNA of 4.3 log10 copies/mL. HBV variants harboring DNA polymerase mutations (RTT128N and RTR153Q or RTW153Q, associated with hepatitis B immunoglobulin resistance) were sensitive to adefovir in vitro. In vitro studies demonstrated that HBV expressing the adefovir-resistant RTN236T mutation had a 2- to 3-fold reduced sensitivity to lamivudine, while HBV harboring the adefovir-resistant RTA181V mutation had a 3-fold reduced sensitivity to lamivudine. Toxicology Studies: Chronic Toxicity: In animal studies, tubular nephropathy, characterized by histological changes and/or elevated blood urea nitrogen and serum creatinine, was the primary dose-limiting toxicity of adefovir dipivoxil. The nephrotoxicity observed in animal studies occurred at exposures approximately 3 to 10 times that of the recommended human therapeutic dose (10 mg/day). Genotoxicity: In the in vitro mouse lymphocytoma test (with or without metabolic activation), adefovir dipivoxil was mutagenic. In the human peripheral blood lymphocyte test, adefovir dipivoxil induced chromosomal aberrations without metabolic activation. The mouse micronucleus test results for adefovir dipivoxil were negative, and the AMES test results for adefovir with or without metabolic activation were negative. Reproductive toxicity: No effects on rat fertility were observed at exposures approximately 19 times that of the human therapeutic dose. Oral administration of adefovir dipivoxil to rats and rabbits (exposures approximately 23 and 40 times that of the human therapeutic dose of 10 mg/day, respectively) did not result in embryotoxicity or teratogenicity. Intravenous administration of adefovir to pregnant rats resulted in an increased incidence of embryotoxicity and fetal malformations (systemic edema, sunken eyes, umbilical hernia, and tail kinking) at doses that produced significant maternal toxicity (equivalent to 38 times the human exposure). No adverse effects were observed at intravenous doses equivalent to 12 times the human exposure. Carcinogenicity: Oral administration of adefovir dipivoxil to mice and rats at doses equivalent to 10 times and 4 times the human therapeutic dose, respectively, did not result in carcinogenic effects.
[Storage Instructions]
Store in a cool, dry place (not exceeding 20°C) in a tightly sealed container.
Drug Instructions]
Please read the instructions carefully and use as directed, or purchase and use under the guidance of a pharmacist.
