Product Overview
[Drug Name]
Generic Name: Adefovir Dipivoxil Tablets
Trade Name: Yilaifen
English Name: Adefovir Dipivoxil Tablets
Chinese Pinyin: Adefuweizhi Pian
[Ingredients]
The main ingredient of this product is adefovir dipivoxil. Excipients: Pregelatinized starch (gluten-free); cross-linked sodium carboxymethyl cellulose; lactose monohydrate; talc; magnesium stearate.
[Appearance]
This product is an off-white tablet.
[Indications]
This product is 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 the treatment of chronic hepatitis B.
Adults (18-65 years)
For patients with normal renal function, the recommended dose is 10 mg once daily. This indication is based primarily on the results of a 48-week clinical trial. The optimal duration of treatment has not been determined. Do not exceed the recommended dose. The relationship between treatment efficacy and long-term clinical outcomes (e.g., hepatocellular carcinoma or decompensated cirrhosis) has not been established.
Patients should regularly monitor hepatitis B biochemical, virological, and serum markers at least every 6 months.
Discontinuation of treatment may be considered in the following circumstances:
Based on experience with lamivudine, HBeAg-positive patients experiencing HBeAg seroconversion while receiving this drug may experience HBeAg seroconversion. After the switch, treatment should continue for 6 months. If testing confirms sustained efficacy, discontinuation of treatment may be considered. For HBeAg-negative patients, long-term treatment is recommended, at least until HBsAg seroconversion occurs or the drug is discontinued due to loss of efficacy. Discontinuation of treatment should be carefully weighed against the risks and benefits. Patients should be closely monitored by an experienced physician.
Discontinuation of treatment is not recommended for patients who develop decompensated liver disease or decompensated cirrhosis during treatment.
Patients with Renal Impairment
Adefovir is excreted renally, so the dosing interval may need to be adjusted in patients with renal impairment. Creatinine clearance >50 mL/min, no dosing interval adjustment is required. Detailed dosing interval adjustments for patients with creatinine clearance <50 mL/min are provided in the table below. Dosing frequency should not exceed the recommended frequency in the table (see [Precautions] - Renal Function). Although pharmacokinetic studies have included patients with renal impairment, these guidelines for dosing interval adjustment have not been clinically evaluated for safety and efficacy. Therefore, these patients should be closely monitored for clinical efficacy. Studies have not been conducted in patients with creatinine clearance below 10 mL/min. Therefore, no recommended dosing regimen is available.
For patients with creatinine clearance of 20-49 mL/min, the recommended dose is 10 mg, administered every 48 hours.
For patients with creatinine clearance of 10-19 mL/min, the recommended dose is 10 mg, administered every 72 hours.
For patients undergoing hemodialysis, 10 mg is administered after dialysis. mg once every 7 days (the recommended dosing regimen is based on results from studies with three high-flow dialysis sessions per week).
Patients with Impaired Liver Function
No dosage adjustment is required for patients with impaired liver function (see [Pharmacokinetics] - Patients with Impaired Liver Function).
[Adverse Reactions]
Common adverse reactions in international clinical studies were asthenia, headache, abdominal pain, nausea, flatulence, diarrhea, and dyspepsia. Adverse reactions in domestic clinical studies were leukopenia (mild), diarrhea (mild), and alopecia (moderate). One serious adverse event occurred in a clinical study: a case of acute myeloid leukemia M3 after 29 weeks of treatment with adefovir, which the investigators determined was not related to adefovir.
[Contraindications]
Adefovir dipivoxil is contraindicated in patients with confirmed hypersensitivity to any component of this product.
[Precautions]
1. Acute exacerbation of hepatitis B may occur if patients discontinue hepatitis B treatment, including discontinuation of adefovir dipivoxil. Therefore, patients who discontinue hepatitis B treatment should closely monitor their liver function and, if necessary, resume anti-hepatitis B treatment. Chronic treatment with adefovir dipivoxil can cause nephrotoxicity in patients with renal impairment or at risk for renal impairment. Renal function should be closely monitored and the dose adjusted appropriately in these patients. Before treatment with adefovir dipivoxil, all patients should be tested for human immunodeficiency virus (HIV) antibodies. Use of anti-hepatitis B drugs, such as adefovir dipivoxil, can affect unknown or untreated HIV in patients with chronic hepatitis B, potentially leading to HIV resistance. Nucleoside analogs, used alone or in combination with other antiretroviral drugs, can cause lactic acidosis and severe hepatomegaly with steatosis, including fatal events. Because the risk to the developing human embryo is unknown, women of childbearing age treated with adefovir dipivoxil are advised to use effective contraception.
[Use in Special Populations]
Precautions for Children:
The efficacy and safety of Hevivir in patients under 18 years of age have not been established (see [Precautions] - Other). Adefovir dipivoxil should not be used in children and adolescents.
Precautions for Pregnancy and Lactation:
Pregnancy: There is insufficient data on the use of adefovir dipivoxil in pregnant women. Animal studies of intravenous adefovir have shown reproductive toxicity (see [Pharmacology and Toxicology] - Clinical Safety Data). Pregnant women should avoid using adefovir dipivoxil as much as possible. If it is necessary to use it, the pros and cons should be weighed. The use of adefovir dipivoxil during pregnancy can only be considered when the potential benefits definitely outweigh the risks to the fetus. There is currently no data on the effect of adefovir dipivoxil on mother-to-child transmission of HBV. Therefore, infants should be immunized according to standard recommendations to prevent neonatal HBV infection. Because the potential risk to the developing human embryo is not clear, it is recommended that women of childbearing age treated with adefovir dipivoxil take effective contraceptive measures. Lactation: It is not known whether adefovir is excreted in human breast milk. Therefore, mothers taking adefovir dipivoxil should be advised not to breastfeed their infants.
Precautions for Elderly Patients:
The efficacy and safety of Hevivir in patients over 65 years of age have not been established (see [Precautions] - Other).
[Drug Interactions]
Adefovir dipivoxil is rapidly converted to adefovir in vivo. At concentrations significantly higher than those observed in vivo (>4000-fold), adefovir does not inhibit 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 unknown whether adefovir induces CYP450 enzymes. Based on in vitro results and the renal elimination pathway of adefovir, the potential for CYP450-mediated drug interactions with other drugs, either as an inhibitor or substrate, is low. Adefovir is excreted through the kidneys via glomerular filtration and active tubular secretion. Coadministration of 10 mg of adefovir dipivoxil with other drugs secreted through the renal tubules or drugs that alter renal tubular secretion may increase the serum concentration of adefovir dipivoxil or the coadministered drug. Coadministration of 10 mg of adefovir dipivoxil with 100 mg of lamivudine did not alter the pharmacokinetic properties of either drug. Caution should be exercised when coadministering 10 mg of adefovir dipivoxil with drugs secreted through the renal tubules, as the two drugs compete for the same elimination pathway, potentially increasing the serum concentration of adefovir or the coadministered drug.
[Pharmacological Action]
Mechanism of Action: Adefovir is an acyclic nucleoside analog of adenosine monophosphate that is phosphorylated by cellular kinases to its active metabolite, adefovir diphosphate. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) through two mechanisms: competition with the natural substrate deoxyadenosine triphosphate and incorporation into the viral DNA. Adefovir diphosphate causes DNA chain elongation termination after HBV DNA polymerase A. The inhibition constant (Ki) of adefovir diphosphate against HBV DNA polymerase is 0.1 μM, 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.
Storage: Store tightly in a dry place below 25°C.
Specifications: 10 mg
Packaging: 10 mg x 30 seconds per box
Expiry Life: 48 months.
Approval Number: National Medicine Standard H20080032
Manufacturer: Qilu Pharmaceutical Co., Ltd.
