Product Overview
[Drug Name]
Generic Name: Tenofovir Alafenamide Fumarate Tablets
Trade Name: Kunzhicheng Tenofovir Alafenamide Fumarate Tablets 25mg x 30 Tablets
[Main Ingredients]
Tenofovir Alafenamide Fumarate.
[Indications/Main Functions]
Indicated for the treatment of chronic hepatitis B in adults and adolescents (aged 12 years and older, weighing at least 35 kg).
Specifications]
25mg x 30 tablets
[Dosage and Administration]
Treatment should be initiated by a physician experienced in the management of chronic hepatitis B. Adults and adolescents (aged 12 years and older, weighing at least 35 kg): Take one tablet once daily, orally. To be taken with food. 1. Missed Dose: If a dose is missed, the patient will be discharged. If it is less than 18 hours past the usual time of taking the medication, the patient should take one dose as soon as possible and resume the normal dosing schedule. If it is more than 18 hours past the usual time of taking the medication, the patient should not take the missed dose and should only resume the normal dosing schedule. If the patient vomits within 1 hour after taking the medication, the patient should take another tablet. If the patient vomits more than 1 hour after taking the medication, the patient does not need to take another tablet. 2. Special populations: 1. Elderly: No dose adjustment is required for patients aged 65 years and over (see Pharmacology and Toxicology). 2. Renal impairment: For adults or adolescents (aged at least 12 years and weighing at least 35k) with an estimated creatinine clearance (CrC) ≥15mL/min No dose adjustment is required for patients with CrCl <15 mL/min or those undergoing hemodialysis. On the day of hemodialysis, the drug should be administered after completion of hemodialysis treatment (see [Pharmacology and Toxicology]). No dosage recommendation is available for patients with CrCl <15 mL/min who are not undergoing hemodialysis (see [Pharmacology and Toxicology]). 3. Hepatic Impairment: No dose adjustment is required for patients with hepatic impairment (see Precautions and [Pharmacology and Toxicology]). 4. Pediatric Population: The safety and efficacy of tenofofen alafenamide fumarate tablets have not been established in children under 12 years of age or weighing <35 kg. No data are available.
[Adverse Reactions]
Summary of Safety Characteristics in Overseas Patients: Adverse Reactions Review The estimate is based on pooled safety data from 2 controlled Phase 3 studies in which 866 HBV-infected patients received tenofovir alafenamide 25 mg once daily in a double-blind manner through week 96 (median duration of blinded study drug exposure was 104 weeks). The most commonly reported adverse reactions were headache (12%), nausea (6%), and fatigue (6%). After week 96, patients continued to receive their original blinded treatment or received open-label tenofovir. No other adverse reactions to tenofovir alafenamide were observed in the subgroup of subjects receiving open-label tenofovir during the double-blind period from week 96 to week 120 (see [Pharmacology and Toxicology]). Adverse Reactions Summary Table The following have been observed with the use of tenofovir alafenamide in patients with chronic hepatitis B. Adverse drug reactions (Table 1). The following is based on the 96th week analysis of overseas studies and is divided into body system organs and frequency. The frequency limits are as follows: common (10 to 10), rare (<1000 to 1/1000), or rare (<1/100). Table 1 Adverse reactions found in overseas subjects when using tenofovir alafenamide System organ classification Frequency Adverse reactions Gastrointestinal diseases Common: diarrhea, vomiting, nausea, abdominal pain, abdominal distension, flatulence Systemic diseases and medication site conditions Common: fatigue Neurological diseases Very Summary of safety characteristics of overseas patients Adverse reaction evaluation is based on the pooled safety data from two controlled Phase 3 studies in which 866 HBV-infected patients were enrolled in a double-blind manner. Patients received tenofovir alafenamide 25 mg once daily until week 96 (median duration of blinded study drug exposure was 104 weeks). The most commonly reported adverse reactions were headache (12%), nausea (6%), and fatigue (6%). After week 96, patients continued to receive their original blinded treatment or open-label tenofovir alafenamide. No other adverse reactions were observed in the subgroup of subjects receiving open-label tenofovir alafenamide during the double-blind period from week 96 to week 120 (see [Pharmacology and Toxicology]). Adverse Reactions Summary Table: The following adverse drug reactions have been observed with tenofovir alafenamide in patients with chronic hepatitis B (Table 1). The following is an analysis based on week 96 of an overseas study by body system. Adverse reactions are listed by organ class and frequency
(<110,0). Table 1: Frequency of adverse reactions by system organ class observed in overseas subjects using tenofovir alafenamide. Adverse reactions Gastrointestinal disorders Common: diarrhea, vomiting, nausea, abdominal pain, bloating, flatulence Systemic disorders and administration site conditions Common: fatigue Neurological disorders Very common: headache Common: dizziness Skin and subcutaneous tissue disorders Common: rash, pruritus Hepatobiliary disorders Common: increased alanine aminotransferase Musculoskeletal and connective tissue disorders Common: joint pain Safety profile in mainland China patients Summary of adverse reactions in mainland China patients The evaluation of adverse reactions in mainland China patients was based on two Phase 3 studies (in which 227 mainland China HBV-infected patients received 25 mg once daily tenofovir alafenamide). The safety profile of tenofovir alafenamide in HBV-infected patients in mainland China was generally consistent with the safety profile observed in two overseas Phase 3 studies. No patients in mainland China discontinued tenofovir alafenamide treatment due to adverse events. Reporting of suspected adverse reactions Post-approval reporting of suspected adverse reactions is important. This allows for continuous monitoring of the benefit/risk balance of the drug's use. In China, healthcare professionals are required to report any suspected adverse reactions through the national reporting system. Common: Headache Common: Dizziness Skin and subcutaneous tissue disorders Common: Rash, itching Hepatobiliary disorders Common: Increased alanine aminotransferase Muscle Summary of safety profile of common joint pain in bone and connective tissue diseases in mainland China Adverse reactions in mainland China patients were evaluated based on safety data analyzed up to week 96 in two Phase 3 studies in which 27 mainland China HBV-infected patients received 25 mg of tenofovir alafenamide once daily. The safety profile of tenofovir alafenamide in mainland China HBV-infected patients was generally consistent with the safety profile observed in two overseas Phase 3 studies. No mainland China patient discontinued tenofovir alafenamide treatment due to adverse events. Reporting of suspected adverse reactions Post-approval reporting of suspected adverse reactions is important. This allows for continuous monitoring of the benefit/risk balance of the drug. In China, it is required Healthcare professionals should report any suspected adverse reactions through the national reporting system.
[Contraindications]
Hypersensitivity to the active ingredient or any of the following excipients: alpha-lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide.
[Precautions]
1. Hepatitis exacerbation warning after discontinuation of treatment: Acute exacerbations of hepatitis (usually associated with elevated plasma HBV DNA levels) have been reported in patients who discontinue hepatitis B treatment. Some cases are self-limited, but severe exacerbations (including fatal outcomes) may occur after discontinuation of hepatitis B treatment. Hepatitis B treatment should be discontinued for at least 6 months. Liver function should be monitored regularly with clinical and laboratory follow-up over the next month, and if appropriate, hepatitis B treatment may need to be resumed. In patients with advanced liver disease or cirrhosis, discontinuation of treatment is not recommended because worsening of hepatitis after treatment may lead to decompensation of liver function. In patients with decompensated liver disease, liver flares are particularly severe and sometimes fatal, and spontaneous exacerbations of chronic hepatitis B are relatively common during treatment, characterized by a transient increase in serum alanine aminotransferase (ALT). After initiating antiviral treatment, some patients may experience an increase in serum ALT. In patients with compensated liver disease, such increases in serum ALT are usually not accompanied by an increase in serum bilirubin concentration or decompensation of liver function. Patients with cirrhosis are at increased risk of hepatitis B. The risk of liver decompensation after deterioration may be higher, so it should be closely monitored during treatment. 2. HBV transmission Patients must be informed that tenofovir alafenamide fumarate tablets cannot prevent the risk of HBV transmission through sexual contact or blood contamination. Appropriate preventive measures must continue to be taken. 3. Patients with decompensated liver disease There is no data on the safety and efficacy of this product for patients with decompensated liver disease and HBV infection with a ChidPughturoteCP score >9 (i.e., grade C). These patients may be at higher risk of severe liver or kidney adverse reactions. Therefore, the various hepatobiliary and kidney indicators and parameters of this patient population should be closely monitored (see [Pharmacology and Toxicology]). 4 Lactic acidosis/severe hepatomegaly: Lactic acidosis and severe hepatomegaly, including fatal cases, have been reported with nucleoside analogs (including tenofovir disoproxil fumarate or other tenofovir prodrugs) used alone or in combination with other antiretroviral drugs. Treatment with this drug should be withheld in any patient with clinical or laboratory findings suggestive of lactic acidosis or significant hepatotoxicity (which may include hepatomegaly and steatosis, even in the absence of significant transaminase elevations). 5. Renal impairment: Patients with creatinine clearance <30 mL/min should be treated with creatinine clearance <30 mL/min. Patients with CrCl ≥15 mL/min but <30 mL/min should be treated with creatinine clearance <15 mL/min. n and in patients who are receiving hemodialysis, the use of this product once daily is based on extremely limited pharmacokinetic data and modeling and simulation. There are no safety data on the use of this product to treat HBV-infected patients with CrCl <30mL/min. This product is not recommended for patients with CrC <15mLmin who are not receiving hemodialysis (see [Dosage and Administration]). 6. Nephrotoxicity The potential risk of nephrotoxicity caused by long-term exposure to low levels of tenofovir due to the administration of tenofovir alafenamide cannot be ruled out (see [Pharmacology and Toxicology]). 7. Patients co-infected with HBV and hepatitis C or hepatitis D virus There is no information on the safety of this product in patients co-infected with hepatitis C or hepatitis D virus. The data on the efficacy and safety of this product have not been established. Before starting treatment with this product, all HBV-infected patients should undergo HIV antibody testing. If the test result is positive, the corresponding antiretroviral combination regimen recommended for patients co-infected with HV-1 should be used. 9. Combination with other drugs This product should not be used in combination with products containing tenofovir disoproxil fumarate, tenofovir disoproxil fumarate, or tenofovir disoproxil fumarate. 10. Intolerance: This product contains lactose. Therefore, patients with galactose intolerance, Lap lactase deficiency, or the rare transfusion problem of glucose-galactose malabsorption should not take this product. 11. Effects on Ability to Drive and Use Machinery: This product has no or negligible effect on the ability to drive and use machinery. Patients should be informed that dizziness has been reported during treatment with this product.
[Pediatric Use]
The safety and efficacy of tenofovir alafenamide fumarate tablets have not been established in children under 12 years of age or weighing <35 kg. No data are available.
[Elderly Use]
No dosage adjustment is required for tenofovir alafenamide fumarate tablets in patients aged 65 years and older (see [Pharmacology and Toxicology]).
