Adefovir Dipivoxil Capsules

This product, adefovir dipivoxil, is an oral antiviral drug. Adefovir dipivoxil is metabolized in the body to adefovir, which is an acyclic nucleoside analog of adenosine monophosphate. Under the action of cellular kinases, it is further phosphorylated to an active metabolite, adefovir diphosphate. 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 0.1μM, but the inhibitory effect on human DNA polymerase α and γ is weak, with Ki values of 1.18μM and 0.97μM, respectively. Antiviral activity: In human hepatoma cell lines transfected with HBV, the concentration (IC50) of adefovir to inhibit 50% viral DNA replication is 0.2-2.5μM. Drug resistance: Long-term drug resistance analysis (96-144 weeks) was conducted on patients who still had detectable serum HBV DNA after receiving adefovir dipivoxil treatment, and rtN236T and rtA181V mutations were identified as being associated with adefovir resistance. In vitro studies have found that the rtN236T mutation causes HBV to be 4-14 times less sensitive to adefovir, and 6/6 patients with this mutation had a rebound in serum HBV DNA. The rtAl81V mutation causes HBV to be 2.5-3 times less sensitive to adefovir, and 2/3 patients with this mutation had a rebound. 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 containing lamivudine-resistant mutations (rtL180M, rtM204I, rtM204V, rtL180MrtM204V, rtVl73L) on the HBV DNA polymerase gene are sensitive to adefovir in vitro. In patients with lamivudine-resistant variant HBV, adefovir dipivoxil also showed anti-HBV effects, with a median decrease in serum HBV DNA of 4.3 log10 copies/ml. HBV variants containing DNA polymerase mutations (rtTl28N and rtRl53Q or rtWl53Q, associated with hepatitis B immunoglobulin resistance) are sensitive to adefovir in vitro. In vitro studies have shown that HBV expressing the rtN236T mutation associated with adefovir resistance has a 2- to 3-fold reduced sensitivity to lamivudine, while HBV expressing the rtAl81V mutation associated with adefovir resistance has a 3-fold reduced sensitivity to lamivudine.

The main ingredient is adefovir dipivoxil, whose chemical name is: 9-[2-[di(pivaloyloxy)methoxy]phosphinyl]methoxy}ethyl]adenine Molecular formula: C20H32N5O8P Molecular weight: 501.48

This product is a hard capsule, and the contents are white or off-white granules or powder.

This product is suitable for the treatment of adult patients with chronic hepatitis B who have evidence of active replication of hepatitis B virus and compensated liver function with persistent elevation of serum amino acid transferase (ALT or AST) or active liver histological lesions.

Patients must use this product under the guidance of a physician who has experience in treating chronic hepatitis B. For adults (18 to 65 years old), the recommended dose of this product is 1 tablet (10 mg) once a day, orally before or after meals. The optimal course of treatment has not yet been determined. Do not exceed the recommended dose. Patients should regularly monitor hepatitis B biochemical indicators, virological indicators and serum markers, at least once every 6 months.

Literature reports show that common adverse reactions in foreign clinical studies are weakness, headache, abdominal pain, nausea, (gastrointestinal) flatulence, diarrhea, and indigestion. In domestic clinical studies, the adverse events that may be related to the drug as judged by the researchers are as follows: hair loss, rash, dizziness, headache, liver pain, rib distension, stomach discomfort, fatigue, nausea, and abnormal laboratory tests (elevated ALT and CPK, leukopenia). The overall incidence of any single adverse event is ≤2%. No serious adverse events related to the drug were observed.

Adefovir dipivoxil is contraindicated in patients with confirmed hypersensitivity to any component of this product.

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: The effects of pregnant women and adefovir dipivoxil on mother-to-child transmission of HBV have not been studied. Therefore, infants should be immunized to prevent them from being infected with hepatitis B virus. It is not known whether adefovir is secreted into human breast milk. 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 of age have not been determined.

Adefovir dipivoxil is rapidly converted to adefovir in vivo. 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, adefovir is unlikely to interact with other drugs mediated by CYP450 as an inhibitor or substrate. Adefovir is excreted by the kidneys through glomerular filtration and active tubular secretion. The combined use of 10 mg adefovir dipivoxil with other drugs secreted by the renal tubules or drugs that change the secretion function of the renal tubules can increase the serum concentration of adefovir dipivoxil or the combined drug. When 10 mg adefovir dipivoxil is used in combination with 100 mg lamivudine, the pharmacokinetic characteristics of both drugs are not changed. Caution should be exercised when 10 mg of adefovir dipivoxil is used in combination with drugs that are actively secreted by the renal tubules, because the two drugs compete for the same elimination pathway, which may cause an increase in the serum concentration of adefovir or the co-administered drug.

Seal and store in a dry place at 2-20℃. The validity period is tentatively 24 months.

10mg

24 months

Zhuhai United Pharmaceutical Co., Ltd. Zhongshan Branch

• Founded in:

  1997-07-28

• Address:

  No. 12, Jialian Road, Tanzhou Town, Zhongshan City, Guangdong Province

• Tax NO.:

  91442000X180811958

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