Adefovir Dipivoxil Tablets

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. It is further phosphorylated to an active metabolite, adefovir diphosphate, under the action of cellular kinases. Adefovir diphosphate inhibits HBVDNA polymerase (reverse transcriptase) in the following two ways: one is to compete with the natural substrate deoxyadenosine triphosphate, and the other is to cause the termination of DNA chain extension after integration into viral DNA. The inhibition constant (KI) of adefovir diphosphate on HBVDNA 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 that inhibits 50% viral DNA replication is 0.2-2.5μM. Drug resistance: Long-term resistance analysis (96-144 weeks) was performed on patients who still had detectable serum HBV DNA after receiving adefovir dipivoxil treatment, and the RTN236T and RT181V mutations were identified as being associated with adefovir resistance. In vitro studies have found that the RTN236T mutation causes a 4- to 14-fold decrease in HBV sensitivity to adefovir, and 6/6 patients with this mutation had a rebound in serum HBV DNA. The RT181V mutation causes a 2.5- to 3-fold decrease in HBV sensitivity 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, RTL180RMRTM204V, 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.

Adefovir dipivoxil

This product is white to 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. The recommended dose for adults (18 to 65 years old) is 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.

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 type M3 after taking this product for 29 weeks. The researchers judged that it was not related to this product. The most important adverse reaction is that the use of adefovir dipivoxil has a strong potential for renal toxicity, and once the drug is stopped, the patient is likely to experience worsening of hepatitis.

Adefovir dipivoxil is contraindicated in patients who have 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: There is insufficient data on the use of adefovir dipivoxil in pregnant women. The use of adefovir dipivoxil during pregnancy can only be considered 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 standard recommended regimens to prevent neonatal infection with HBV. It is not yet known whether adefovir will be secreted into human milk, and women in the lactation period should avoid breastfeeding when using this product. Precautions for the elderly: The efficacy and safety of this product in elderly patients over 65 years old have not yet 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, the possibility of adefovir as an inhibitor or substrate, mediated by CYP450 and other drugs is very small. Adefovir is excreted through the kidneys by glomerular filtration and active tubular secretion. The combination 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 combined with 100 mg lamivudine, the pharmacokinetic properties 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.

Keep away from light, sealed, cool and dry.

10 mg

24 months.