Adefovir Dipivoxil Tablets

Pharmacological action Mechanism of action: Adefovir is an acyclic nucleoside analog of adenosine monophosphate, which 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 elongation termination after integration into viral DNA. The inhibition constant (Ki) of adefovir diphosphate on HBV DNA polymerase is 0.1mu;M, but the inhibitory effect on human DNA polymerase alpha; and gamma; is weak, with Ki values of 1.18mu;M and 0.97mu;M, respectively. Antiviral activity: In human hepatoma cell lines transfected with HBV, the concentration (IC50) of adefovir to inhibit 50% viral DNA replication is 0.2-2.5uM. 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 rtA181V 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 resistance-related mutations (rtL_180M, rtm204I, rtm204V, rtL180Mrtm204V, rtV173L) on the HBV DNA polymerase gene are sensitive to adefovir in vitro. In patients with lamivudine resistance-related 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 (rtT128N and rtR153Q or rtW153Q, 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 rtA181V mutation associated with adefovir resistance has a 3-fold reduced sensitivity to lamivudine.

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

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. Adults (18-65 years old): The recommended dose of this product 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 fatigue, leukopenia (mild), diarrhea (mild), alopecia (moderate), abnormal urine protein, increased creatinine and reversible increase in liver transaminases.

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, 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. The combination of 10 mg of 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. The pharmacokinetic properties of both drugs are not changed when 10 mg of adefovir dipivoxil is combined with 100 mg of lamivudine. 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.

Store in a cool, sealed place.

10mg

Tentatively 18 months.

Tipr Pharmaceutical Co., Ltd.

• Founded in:

  1994-08-18

• Address:

  No. 29, Huixin Road, Binhai Science and Technology Park, Binhai Hi-tech Zone, Tianjin

• Tax NO.:

  91120116238991799D

• Registered Funds:

  50 million yuan

• Website:

  Log in to view

• Email:

  Log in to view