Epivir
Lamivudine
CAS: 134678-17-4;131086-21-0
Molecular Formula: C8H11N3O3S
Epivir - Names and Identifiers
Epivir - Physico-chemical Properties
| Molecular Formula | C8H11N3O3S |
| Molar Mass | 229.26 |
| Density | 1.73±0.1 g/cm3(Predicted) |
| Melting Point | 177 °C |
| Boling Point | 475.4±55.0 °C(Predicted) |
| Specific Rotation(α) | D21 -135° (c = 0.38 in methanol) |
| Flash Point | 9℃ |
| Water Solubility | 70g/L(temperature not stated) |
| Solubility | water: soluble10mg/mL, clear |
| Vapor Presure | 4.91E-11mmHg at 25°C |
| Appearance | White crystalline powder |
| Color | white to beige |
| Merck | 14,5352 |
| pKa | 13.83±0.10(Predicted) |
| Storage Condition | 2-8°C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| Refractive Index | -142 ° (C=1, MeOH) |
| MDL | MFCD00869739 |
| Physical and Chemical Properties | A white solid was obtained from methanol-ethyl acetate. [Α] D21-132 °(C = 1.08, methanol). Or from the boiling ethanol crystallization, melting point of 160~162 deg C. [Α] D21-135 °(C = 0.38, methanol). |
| Use | Antivirals for the treatment of hepatobiliary disorders |
Epivir - Risk and Safety
| Risk Codes | R63 - Possible risk of harm to the unborn child R36/37/38 - Irritating to eyes, respiratory system and skin. |
| Safety Description | S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36 - Wear suitable protective clothing. |
| UN IDs | UN1230 - class 3 - PG 2 - Methanol, solution |
| WGK Germany | 3 |
| RTECS | UW7361333 |
| HS Code | 29349990 |
Epivir - Reference
| Reference Show more | 1. Gong Hongfei, Pang Fuhua, Rui Ying, et al. Three kinds of anti-HBV nucleoside (acid) are similar to anti-hepatitis B virus in vitro [J]. Experimental Technology and Management 2019 036(009):45-48 56. 2. An Qiong Yang Jianxia Zhao Xiuli et al. Response Surface Optimization Cloud Point Extraction Combined with HILIC Determination of Four Anti-AIDS Drugs in Rat Serum [J]. Journal of Sun Yat-sen University (Medical Edition) 2020 041(001): p.149 -160. 3. [IF = 7.963] Chenzhi Hou et al."Estimating the prevalence of hepatitis B by wastewater-based epidemiology in 19 cities in China." Sci Total Environ. 2020 Oct;740:139696 |
Epivir - Expand reading
at present, it is recognized that the most effective anti-HBV drugs are interferon and a new generation of nucleoside analogs represented by lamivudine. As the first approved oral anti-HBV drug, the advent of lamivudine has promoted the progress of chronic hepatitis B treatment, marking the entry of chronic hepatitis B treatment into nucleoside analog therapy.
recently the United States, Europe, Canada, Australia, Singapore, Hong Kong, China and other countries and regions have approved the adefovir (adefovir) listing, for the treatment of chronic hepatitis B added new hope. With the wide clinical application of lamivudine, but also encountered some similar problems with previous treatment, such as sustained response rate is not satisfied, some patients relapse after drug withdrawal, the need for long-term medication and drug resistance variation.
since 1999, China has developed or listed new "clinical application of lamivudine guidance" and "Lamivudine clinical application expert consensus" for clinicians reasonable, scientific, the correct use of lamivudine plays an important role. On this basis, according to the latest experience of using lamivudine in China, and referring to the consensus and guidelines of the Asia Pacific Liver Association, the European Liver Association and the American Liver Association, based on the latest literature at home and abroad, the 2003 expert consensus on clinical application of lamivudine was updated to provide further reference for Chinese clinicians.
Last Update：2023-08-16 23:52:17
Epivir - Nature
Open Data Verified Data
A white solid was obtained from methanol-ethyl acetate. [a]21 -1320(c -1.08. Methanol). Or from the boiling ethanol crystallization, melting point of 160~162 deg C. -135. (c = 0.38, methanol).
Last Update：2024-01-02 23:10:35
Epivir - Preparation Method
Open Data Verified Data
5-acetoxy-2-(diphenyl-tert-butylsiloxymethyl) -1.3 pentane and 4-acetamido-2-trimethylsiloxypyrimidine dissolved in dichloroethane, condensed under Lewis acid catalysis, and then hydrolyzed with ammonia-methanol to remove acetyl group, finally, in Tetrahydrofuran, the trimethylsilyl group is removed by hydrolysis with Tetra-N-butylammonium fluoride to obtain lamivudine.
Last Update：2022-01-01 09:08:12
Epivir - Standard
Authoritative Data Verified Data
This product is (a)-1-[(2R,5S)-2-(hydroxymethyl)-l, 3-oxosulfur heterocyclic pentane -5-yl] cytosine. According to the calculation of water and solvent-free, containing lamivudine (C8H11N303S) should be 97.5% ~ 102.0%.
Last Update：2024-01-02 23:10:35
Epivir - Trait
Authoritative Data Verified Data
- This product is white or off-white crystalline powder.
- This product is dissolved in water, slightly soluble in methanol.
melting point
The melting point of this product (General 0612) is 174~179°C.
specific rotation
take this product, precision weighing, add water to dissolve and quantitatively dilute to make a solution containing about 5mg per lml, and determine according to law (General rule 0621), the specific rotation was from 97 ° to -99 °.
Last Update：2022-01-01 13:34:40
Epivir - Pharmacology, Toxicology and Pharmacokinetics
1. Pharmacology and toxicology
Lamivudine is a nucleoside anti-Virus drug, which has a strong inhibitory effect on hepatitis B Virus (HBV) in vitro and in experimental infected animals. Lamivudine can be metabolized in HBV infected cells and normal cells to produce lamivudine triphosphate, which is the active form of lamivudine. It is both an inhibitor of HBV polymerase and a substrate of this polymerase. Lamivudine triphosphate was incorporated into Virus of the DNA strands, blocking Virus of DNA synthesis.
Lamivudine triphosphate does not interfere with the metabolism of deoxynucleoside in normal cells. It has weak inhibitory effect on mammalian DNA polymerase α and β, and has little effect on the DNA content of mammalian cells. Lamivudine had no obvious toxicity on the structure, DNA content and function of mitochondria. The results of serum HBV DNA detection in most hepatitis B patients showed that lamivudine could rapidly inhibit HBV replication, and its inhibition continued throughout the treatment process. At the same time, the serum transaminase is reduced to normal. Long-term application can significantly improve the inflammatory changes of liver necrosis and reduce or prevent the progression of liver fibrosis.
2. Pharmacokinetics
After oral administration, lamivudine was well absorbed. About 1hr, the peak plasma concentration of lamivudine reached Cmax1.1-1.5 μg/mL, and the bioavailability was 80-85%. Lamivudine, when taken with food, delays Tmax by 0.25-2.5hr and decreases Cmax by 10-40%, but bioavailability does not change. The results of intravenous administration showed that the average distribution capacity of lamivudine was 1.3L/Kg, the average systemic clearance rate was 0.3L/h/kg, and lamivudine was mainly (>70%). Through the organic cation transport system through the renal clearance, the elimination half-life is 5-7hr. In the therapeutic dose range, the pharmacokinetics of lamivudine was linear, and the plasma protein binding rate was low. In vitro studies showed binding to serum albumin <16-36%.
Lamivudine can enter the cerebrospinal fluid through the blood-brain barrier. Lamivudine is mainly excreted by the kidney with the drug prototype, and the renal excretion accounts for about 70% of the total clearance, and only 5-10% is metabolized into derivatives of trans sulfur oxides. Patients with renal insufficiency will affect the excretion of lamivudine, creatinine clearance rate <30mL/min patients, it is not recommended to use this product. Liver damage does not affect the drug metabolism process of lamivudine. For elderly patients with decreased renal excretion function due to age, there is no significant change in lamivudine metabolism, has an impact.
Last Update：2023-08-16 23:52:17
Epivir - Use
Open Data Verified Data
listed in 1995. In recent years, it is a new anti-hepatitis B Virus drug. Lamivudine is widely accepted as a new nucleoside analog, and it is the most representative nucleoside analog with the best efficacy in clinical application. After marketing in China, the trade name is heptin.
Last Update：2022-01-01 09:08:13
Epivir - Differential diagnosis
Authoritative Data Verified Data
- The infrared absorption spectrum of this product should be consistent with the control spectrum (Spectrum set 975 figure). If not, the product and the lamivudine reference substance are respectively dissolved in methanol, and then volatilized. The infrared absorption spectrum of the product should be consistent with that of the lamivudine reference substance (General rule 0402).
- in the chromatogram recorded under the lamivudine enantiomer examination item, the retention time of the main peak of the test solution should be consistent with the retention time of the lamivudine peak in the system applicable solution.
Last Update：2022-01-01 13:34:41
Epivir - Side effects
hepatitis B patients treated with nucleoside (acid) analogs have to receive long-term treatment or even lifelong treatment. The adverse reactions caused by these drugs have also been widely concerned. The risk of causing solid tumors in animal experiments has plagued doctors and patients. The adverse reactions caused by the application of nucleoside (acid) analogs, such as myopathy, renal toxicity, peripheral neuropathy, lactic acidosis and so on, are the focus of attention. These side effects caused by the drug once appeared but did not take timely measures, is likely to be life-threatening. Therefore, attach great importance to the safety of oral antiviral drugs, regular detection of CK and other indicators, to adhere to long-term treatment plays a positive role. Comparison of 4 kinds of oral antiviral drugs, of which lamivudine has been listed for ten years, is used for the treatment of chronic hepatitis B oral antiviral drugs listed the earliest drug, the most widely applicable population, good safety.
Last Update：2023-08-16 23:52:17
Epivir - Exam
Authoritative Data Verified Data
color of solution
take this product, precision weighing, adding water to dissolve and quantitatively dilute to make a solution containing about 50mg per lml, according to UV-Vis spectrophotometry (General rule 0401), with 4cm quartz absorption cell, at a wavelength of 440nm, the absorbance should not exceed 0.3.
Related substances
take an appropriate amount of this product, accurately weigh, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 0.5mg per lml, as a test solution; Take 1ml for precision, set it in a 100ml measuring flask, dilute it to the scale with mobile phase, then take 5ml with precision, place it in a 50ml measuring flask, dilute it to the scale with mobile phase, and use it as a control solution. The appropriate amount of salicylic acid reference substance was accurately weighed, dissolved and quantitatively diluted with mobile phase to make a solution containing 0.5ug per 1 ml, which was used as the reference solution. According to the chromatographic conditions under the content determination item, 10ul of the test solution, the control solution and the reference solution are respectively injected into the liquid chromatograph, record the chromatogram to 3 times the retention time of the main peak of the test solution. If there are impurity peaks in the chromatogram of the test solution, the peak area of salicylic acid shall not exceed 0.1% based on the external standard method, and the peak areas of other impurities shall be multiplied by their respective correction factors to compare with the main peak area of the control solution, the corrected Peak area of impurity I shall not be more than 3 times (0.3%) the main peak area of the control solution; The corrected Peak area of impurity II shall not be more than 2 times (0.2%) the main peak area of the control solution, the corrected Peak area of other single impurities shall not be greater than the area of the main peak of the control solution (0.1%), and the total amount of impurities shall not exceed 0.6%.
lamivudine enantiomer
take an appropriate amount of this product, add water to dissolve and dilute to make a solution containing about 0.25mg per lml as a test solution; Take 1ml for precision measurement and put it in a 100ml measuring flask, dilute to the scale with water, shake well, then take 3ml accurately, put it in a 10ml measuring flask, dilute to the scale with water, shake well, and use as a control solution. As determined by high performance liquid chromatography (General rule 0512), with β-cyclodextrin bonded silica gel as filler; With 0. The mobile phase was 1 mol/ L ammonium acetate solution-methanol (95:5), and the detection wavelength was 270mn; The column temperature was 15-30 ° C., and the flow rate was 1.0 mL per minute. Take about 2.5mg of lamivudine resolution mixture A reference product (containing lamivudine and lamivudine enantiomers), put it in A 10ml measuring flask, add water to dissolve and dilute to the scale, shake well, and use it as A system applicable solution, lOul was injected into the liquid chromatograph and the chromatogram was recorded. The resolution between the lamivudine peak and the lamivudine enantiomer peak should be not less than 1.5. The sample solution and the control solution were respectively injected with human liquid chromatograph, record chromatogram D The Peak area of lamivudine enantiomer in the chromatogram of the test solution shall not be greater than the main peak area of the control solution (0.3%).
residual solvent
methanol, ethanol, isopropanol, ethyl acetate, isopropyl acetate, dichloromethane, triethylamine, tetrahydrofuran and N, N-dimethylformamide take 0.2ml of 2-pentanone and place it in a measuring flask, dilute to the scale with dimethyl sulfoxide-water (1:1), shake well, as an internal standard stock solution, take 20ml, put it in a 200ml measuring flask, and use Dimethyl Sulfoxide-water (1:1) dilute to the scale, shake, as an internal standard solution; Precision weighing methanol 300mg, absolute ethanol 500mg, isopropanol 500mg, ethyl acetate 500mg, isopropyl acetate 500mg, dichloromethane 60mg, triethylamine lOOmg, tetrahydrofuran (72mg) and N, N-dimethylformamide (88mg) were placed in the same 200ml measuring flask, diluted to the mark with dimethyl sulfoxide-water (1:1), then shaken well, and used as a reference stock solution, take 5ml of precision measurement, put it in a 50ml measuring flask, add 5ml of internal standard stock solution, dilute it to the scale with dimethyl sulfoxide-water (1:1), shake well, and use it as a reference solution; take about 0.5g of this product, precision weighing, precision plus human internal standard solution 10ml, shake to dissolve, as a test solution. According to the determination method of residual solvent (General Principle 0861 third method> determination, using 6% cyanopropylphenyl-94% methyl polysiloxane as stationary liquid capillary column (HP -624,0.53mm X 105m,3um or similar polarity), the inlet temperature is 150°C, the split ratio is 10:1, the initial column temperature is 40°C, keep for 5 minutes, it was then raised to 100°C at a ramp rate of 5°C per minute and then to 200°C at a ramp rate of 10°C per minute for 5 minutes at a carrier gas flow rate of 5ml per minute and a detector temperature of 250°C. 1 u1 of the sample solution and the reference solution shall be accurately measured, respectively injected with human gas chromatograph, and the chromatogram shall be recorded. The peak area ratio shall be calculated according to the internal standard method, and triethylamine shall not exceed 0.032%, and the others shall be in accordance with the regulations.
diethyl ether, n-hexane and toluene precision weighing
take 500mg of diethyl ether, 29mg of N-hexane and 89mg of toluene in a 100ml measuring flask, dilute to the mark with N,N-dimethylacetamide, shake well, and use as a reference stock solution, take 5ml accurately, put it in a 50ml measuring flask, dilute it to the scale with N,N-dimethylacetamide, shake it well, take 5ml accurately, place it in the top empty bottle, and use it as a reference solution; take about 0.5g of this product, precision weighing, top empty bottle, Precision Add 5ml of N,N-dimethylacetamide, shake, as a test solution. According to the determination method of residual solvent (General Principle 0861 second method), the capillary column (HP-94%, 624 m mX 75m, 3um or similar polarity), the inlet temperature is 200°C, the split ratio is 3:1, the initial column temperature is 40°C, keep for 5 minutes, the temperature was then increased to 200°C at a ramp rate of 10°C per minute for 5 minutes, the carrier gas flow rate was 5ml per minute, the detector temperature was 250°C, the headspace bottle equilibrium temperature was 90°C, and the equilibrium time was 30 minutes. The test solution and the reference solution are respectively injected in the headspace, and the chromatogram is recorded. The peak area is calculated according to the external standard method, and shall be in accordance with the regulations.
moisture
take this product, according to the moisture determination method (General 0832 first method 1), the water content shall not exceed 0.2%.
ignition residue
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
Heavy metals
The residue left under the item of taking the ignition residue shall not contain more than 20 parts per million of heavy metal when examined by law (General rule 0821, Law II).
Last Update：2022-01-01 13:34:42
Epivir - Applicable population
suitable for treatment of chronic hepatitis B; According to the National Viral Hepatitis prevention program, diagnosed with chronic hepatitis B, gender is not limited, age 16 years or older, and meet the following criteria:
1, HBeAg positive, DNA HBV positive (DNA HBV positive refers to the dot hybridization method, not PCR positive, there are conditions can be used for quantitative determination of DNA HBV. There is no condition to detect HBV DNA where it can be subject to HBeAg positivity).
2, HBeAg negative, anti-HBe positive, HBV DNA positive, considering the former C region mutation is also suitable for treatment.
3, ALT is higher than normal, bilirubin is lower than 50 mol/L (3.0mg/dL).
Last Update：2023-08-16 23:52:17
Epivir - Content determination
Authoritative Data Verified Data
measured by high performance liquid chromatography (General 0512).
chromatographic conditions and system suitability test
silica gel bonded with eighteen alkyl silane as filler (Zorbax XDB-C18,4.6mm X mm,5um or equivalent column); 0.O25mol/L ammonium acetate solution (take 1.9g of ammonium acetate, add water 900ml to dissolve, adjust pH to 3.8 with glacial acetic acid, dilute to 1000ml with water)-methanol (95:5) as mobile phase; the detection wavelength was 277nm; The column temperature was 35°C. The appropriate amounts of the cytosine control and the uracil control were taken, dissolved and diluted with a mobile phase to prepare a solution containing 10ug per 1 ml, respectively, as a solution (1). Take 5mg of lamivudine resolution mixture B (including lamivudine and impurity II), put it in a 10ml measuring flask, add 2ml of mobile phase, shake to dissolve, then add 1 ml of human solution (l), dilute to scale with mobile phase, shake well, as the system applicable solution, take 10ul injection liquid chromatograph, record chromatogram. The resolution between the peaks of cytosine, uracil, impurity II and lamivudine should meet the requirements.
assay
take an appropriate amount of this product, precision weigh, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 0.25mg per lml, as a test solution, take 10 u1 for precision measurement, injection of human liquid chromatography, record chromatogram; Another precision weighing lamivudine reference substance, the same method for determination. According to the external standard method to calculate the peak area, the result minus the content of lamivudine enantiomer, that is.
Last Update：2022-01-01 13:34:43
Epivir - Usage and dosage
oral, adults each 0.1g, once daily. The optimal dose for children with chronic hepatitis B is 3 mg/kg once a day. After age 12, an adult dose of 100mg once daily is required.
Course of treatment, the new version of the guide in 2011 pointed out: the total course of treatment of hepatitis B should reach at least 2 years. In addition, even if the duration of consolidation therapy reached the indication of withdrawal, the recurrence rate of the patient was lower, which was completely consistent with the opinion of the new edition of Chinese hepatitis B prevention and treatment guidelines in 2010 on the treatment time of patients with chronic hepatitis B. A study on the time of treatment and the recurrence rate of patients showed that: consolidation therapy for less than 1 year, the recurrence rate of patients can reach 61.9%, and the other hand, consolidation therapy for more than 1 year, the recurrence rate was only 8.7%.
Taking Time
Lamivudine can be used for a long time. Lamivudine is the longest time to market, the most clinical experience of antiviral drugs. Long-term standard treatment can effectively reduce and delay disease progression. The guideline states that the ultimate goal of hepatitis B treatment is to "reduce the development of cirrhosis and liver cancer". A landmark 3-year study of 4006 in the field of hepatitis B treatment found that after 32 months of nucleoside drugs (lamivudine), the disease progression can be reduced by 55%, the incidence of liver cancer was reduced by 51%. Lamivudine 10 years follow-up results are found: adhere to long-term oral antiviral therapy can not only make liver fibrosis improved significantly, and even make some patients with early cirrhosis has been reversed.
Last Update：2023-08-16 23:52:17
Epivir - Category
Authoritative Data Verified Data
antiviral drugs.
Last Update：2022-01-01 13:34:43
Epivir - Side effects of long-term use
10% of patients had transient increases in amylase and lipase levels after lamivudine.
2. After long-term use, usually more than 6 months of treatment in patients with HBV Virus DNA polymerase mutation (commonly known as YMDD mutation). However, the study also believes that the continued use of lamivudine in this case still has clinical efficacy.
Lamivudine was well tolerated in all patient populations studied. In Phase II and Phase III clinical trials, there was no increase in the incidence of related adverse reactions due to the increase in the total dose and the extension of the course of treatment. Entecavir is recommended.
Long-term treatment with lamivudine significantly delayed disease progression in patients with HBeAg-positive chronic hepatitis B (P<0.005) and reduced the incidence of liver cirrhosis. Some scholars have studied the long-term efficacy of lamivudine in the treatment of HBeAg positive chronic hepatitis B patients for 5 years. The results showed that lamivudine could inhibit Virus of replication and maintain ALT normalization. The rate of HBeAg seroconversion increased with the prolongation of treatment time, and the proportion of patients with HBeAg seroconversion was 80%.
Although the effect of lamivudine treatment of hepatitis B is obvious, but the use of lamivudine treatment of more than 6 months of hepatitis B can occur Virus mutation. After 1 year of treatment, the incidence of hepatitis B Virus mutation was 10% ~ 20%, and with the extension of treatment time, the mutation rate increased.
Adverse effects of long-term use
Lamivudine is a nucleoside anti-Virus drug, mainly suitable for the treatment of adult patients with chronic hepatitis B, can effectively inhibit the replication of Virus, while promoting the repair and regeneration of damaged liver cells. This drug has a certain therapeutic effect, but should not be taken for a long time, mainly because:
Lamivudine is usually taken for a long period of time, and the course of treatment is long. However, many patients respond to it, and there will be many adverse problems in the long-term use of lamivudine, such as some adverse symptoms, such as dizziness, Head Pain, Fatigue, Nausea, Vomit, indigestion, etc., in fact, these adverse symptoms are not the patients most concerned about, because in addition, long-term use of this drug will lead to drug resistance, and not easy to stop, because once the improper withdrawal, it is likely to cause the disease to rebound again, seriously affect the early treatment, so many patients think that this drug should not be taken for a long time.
2. After long-term use, usually more than 6 months of treatment in patients with HBV Virus DNA polymerase mutation (commonly known as YMDD mutation). However, the study also believes that the continued use of lamivudine in this case still has clinical efficacy.
Lamivudine was well tolerated in all patient populations studied. In Phase II and Phase III clinical trials, there was no increase in the incidence of related adverse reactions due to the increase in the total dose and the extension of the course of treatment. Entecavir is recommended.
Long-term treatment with lamivudine significantly delayed disease progression in patients with HBeAg-positive chronic hepatitis B (P<0.005) and reduced the incidence of liver cirrhosis. Some scholars have studied the long-term efficacy of lamivudine in the treatment of HBeAg positive chronic hepatitis B patients for 5 years. The results showed that lamivudine could inhibit Virus of replication and maintain ALT normalization. The rate of HBeAg seroconversion increased with the prolongation of treatment time, and the proportion of patients with HBeAg seroconversion was 80%.
Although the effect of lamivudine treatment of hepatitis B is obvious, but the use of lamivudine treatment of more than 6 months of hepatitis B can occur Virus mutation. After 1 year of treatment, the incidence of hepatitis B Virus mutation was 10% ~ 20%, and with the extension of treatment time, the mutation rate increased.
Adverse effects of long-term use
Lamivudine is a nucleoside anti-Virus drug, mainly suitable for the treatment of adult patients with chronic hepatitis B, can effectively inhibit the replication of Virus, while promoting the repair and regeneration of damaged liver cells. This drug has a certain therapeutic effect, but should not be taken for a long time, mainly because:
Lamivudine is usually taken for a long period of time, and the course of treatment is long. However, many patients respond to it, and there will be many adverse problems in the long-term use of lamivudine, such as some adverse symptoms, such as dizziness, Head Pain, Fatigue, Nausea, Vomit, indigestion, etc., in fact, these adverse symptoms are not the patients most concerned about, because in addition, long-term use of this drug will lead to drug resistance, and not easy to stop, because once the improper withdrawal, it is likely to cause the disease to rebound again, seriously affect the early treatment, so many patients think that this drug should not be taken for a long time.
Last Update：2023-08-16 23:52:17
Epivir - Storage
Authoritative Data Verified Data
light shielding, sealed storage.
Last Update：2022-01-01 13:34:43
Epivir - Withdrawal criteria
long-term treatment with lamivudine can cause multiple mutation of HBV polymerase gene and drug resistance. After sudden withdrawal, Virus of the mutant strains and the remaining wild strains may become active again, accelerate replication, so some patients will appear after the withdrawal of the "rebound" phenomenon, HBV-DNA, HBeAg back to positive, elevated transaminase, individual patients will even appear jaundice and liver decompensation, illness, thus taking lamivudine should not be stopped suddenly.
The withdrawal of lamivudine is indeed very fastidious and cannot be stopped at will. Experts on the withdrawal of lamivudine is this understanding: 1, lamivudine medication cycle is longer, at least in more than 18 months.
⒉ patients with chronic hepatitis B after 1 year of lamivudine, HBeAg conversion to anti-HBe? On HBV-DNA, the patient turned to negative with normal liver function, and the symptoms disappeared.
⒊ patients with chronic hepatitis B before treatment HBeAg negative, however, HBV-DNA positive, lamivudine must be taken for 2 years, HBV DNA negative can be considered after discontinuation.
⒋ chronic hepatitis B patients in the course of treatment with lamivudine, if the transaminase (ALT) significantly increased to more than 500 units, or even found jaundice, at this time can not be easily discontinued, should be combined with other antiviral drugs (Counseling online doctor), at the same time, combined with high-dose Thymosin and hepatoprotective drugs, symptomatic treatment, until stable condition after half a year to consider drug withdrawal.
The patient received lamivudine for 6 months, with ALT <500 units, and HBV DNA level higher than before treatment, which will not decrease continuously, or switch to other anti-hepatitis B drugs (such as borteli) treatment.
⒍ during the treatment, the patient was found to have Virus YMDD mutation of hepatitis B, with mildly elevated ALT. At this time, the patient continued to take the medicine while observing the disease.
Whether lamivudine will recur after discontinuation depends on the situation in Virus of the body after treatment.
1. Hepatitis B was not completely cleared Virus, which was easy to relapse after drug withdrawal. In order to prevent recurrence after drug withdrawal, it is believed that prolonging the course of treatment or reducing recurrence, so the course of treatment should be 1 to 2 years or longer. Such as recurrence, and then lamivudine treatment, often still effective. It is generally accepted that drug withdrawal should be continued for 3 to 6 months after the e antigen/E antibody serum is turned negative, and the total course of treatment is not less than 1 year.
If Hepatitis B Virus mutation, drug resistance. The variation of the performance of hepatitis B Virus DNA from negative to positive, serum ALT and increased, the mutation occurred in the time of early medication half a year later, a few years later. It is reported that the incidence of drug resistance is 10% ~ 25% in 1 year, with the extension of medication time, drug resistance also increased. If taking lamivudine for more than 6 months, ALT increased, hepatitis B Virus DNA positive or titer increased, should consider the possibility of variation of hepatitis B Virus. However, if ALT is more than 5 times higher than normal and liver function deteriorates, lamivudine should be discontinued and other causes of liver disease should be sought, such as alcohol abuse, drug abuse and other drugs, also be careful if there are other hepatitis virus infections, or complicated with hepatocellular carcinoma, etc. If it is indeed caused by hepatitis B Virus variation, can be replaced by other anti Virus drugs (such as famciclovir), and strengthen the liver treatment.
If recurrence, the treatment is:
(1) the characteristics and precautions of the drug are introduced in detail before administration, and lamivudine is applied on the premise that the patient is committed to following the doctor's advice.
(2) regular reexamination of liver function and Virus replication index during medication, reexamination of liver function 15 days after starting medication, reexamination of liver function 1 time in about 2-4 months after normal liver function. HBV-DNA, the patient was examined once in 1-2 months. HBv-DNA, the patient could be reexamined once in 3 months. 4 months after treatment, HBeAg was reexamined. In general, HBV-DNA and HBeAg negative after consolidation for 3 months before stopping about.
(3) after the patient's condition improves, the patient is often urged to take the drug on time, and the confusion of the so-called "New Drug" and "specific drug" is eliminated in time, so as to prevent the patient from stopping lamivudine and switching to other drugs by himself, causing the recurrence of the disease.
(4) at the end of the course of treatment, the application of interferon and other drugs sequential therapy, or with the combination of antiviral drugs such as oxymatrine. Also can use Lamivudine at the same time with other antiviral drugs, or with traditional Chinese medicine syndrome differentiation and treatment, help to prevent or reduce the recurrence.
(5) after long-term use of lamivudine in a small number of patients with HBv mutation, can be considered to switch to the book or adefovir, it is reported that the mutation of drug resistance has been Virus, the two still have a good effect.
Last Update：2023-08-16 23:52:17
Epivir - EPIVIR（Lamivudine Tablets）
Authoritative Data Verified Data
This product contains lamivudine (C8H11N303S) should be labeled the amount of 90.0% ~ 110.0%.
trait
This product is a film-coated tablet, white or off-white after removal of the coating.
identification
- take an appropriate amount of fine powder of this product (about 0.3g of lamivudine), add 5ml of methanol, shake for 15 minutes to dissolve lamivudine, filter, and evaporate the filtrate to dryness under the condition of slowly flowing nitrogen, the infrared absorption spectrum of the residual Tong should be consistent with the spectrum of the control (Spectrum set 975). If not, take the same method for the determination of lamivudine reference product, the infrared absorption spectrum of this product should be consistent with the lamivudine reference product (General 0402).
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be the same as the retention time of the main peak of the control solution.
examination
- for related substances, take the test solution under the content determination item as the test solution; Take 1ml for precision measurement, put it in a 500ml measuring flask, and dilute it to the scale with mobile phase, shake, as a control solution; Precision weigh the appropriate amount of salicylic acid control, add mobile phase dissolution and quantitative dilution to make a solution containing 0.2ug per 1mL (0.lg specifications) or 0.18ug of solution (0.15g and 0.3g specifications), as a reference solution. According to the chromatographic conditions under the content determination item, the sample solution, the control solution and the reference solution were accurately measured, and the human liquid chromatograph was injected respectively, record the chromatogram of the test solution to 3 times the retention time of the lamivudine peak. If there are impurity peaks in the chromatogram of the test solution, salicylic acid shall not exceed 0.1% of the labeled amount of lamivudine based on the peak area calculated by external standard method, compare the peak area of other known impurities with the main peak area of the control solution after multiplying the respective correction factor, the corrected Peak area of impurity I shall not be greater than 1.5 times (0.3%) of the main peak area of the control solution; the corrected Peak area of impurity II shall not be greater than the main peak area of the control solution (0.2%), and the corrected Peak area of other individual impurities shall not be greater than 0.5 times (0.1%) of the main peak area of the control solution, the total amount of impurities should not exceed 0.6% (see table below for relative retention time and correction factor of each impurity peak). The peaks in the chromatogram of the test solution which were 0.05 times smaller than the main peak area of the control solution were ignored.
- dissolution of this product, according to the dissolution and release determination method (General 0931 second method), with 0.900ml of 1 mol/L hydrochloric acid solution is the dissolution medium, and the rotation speed is 50 revolutions per minute, which is operated according to law. After 30 minutes, 10ml of the solution is taken, filtered, and the filtrate is taken, A solution containing about 6ug of lamivudine per 1 ml was prepared as a test solution by quantitative dilution with a dissolution medium. Measure absorbance at the wavelength of 280mn according to UV-Vis spectrophotometry (General rule 0401); Take appropriate amount of lamivudine reference substance, the dissolution medium was added and dissolved and quantitatively diluted to prepare a solution containing about 1 ml per 1 ml, which was used as a reference solution and measured by the same method, and the dissolution amount of each tablet was calculated. The limit is 85% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler (Zorbax XDB-C18,4.6mm X 250mm, 5um or equivalent performance column); 0.025mol/L ammonium acetate solution (take 1.9g of ammonium acetate, add ml of water to dissolve, adjust pH to 3.8 with glacial acetic acid, dilute to ML with water)-methanol (95:5) as mobile phase; the column temperature was 35°C, and the detection wavelength was 277nm. Appropriate amounts of the cytosine control and the uracil control were taken, dissolved and diluted with a mobile phase to prepare a solution containing 10ug per 1 ml, respectively, as a solution (1). Take 5mg of lamivudine resolution mixture B (containing lamivudine and impurity II), put it in a 10ml measuring flask, add 2ml of mobile phase, shake to dissolve, and then add 1 ml of solution, dilute to the scale with mobile phase, shake, as the system applicable solution, take 10u1 injection liquid chromatograph, record chromatogram. The resolution of each peak between cytosine, uracil, impurity n and lamivudine should meet the requirements.
- determination Method: Take 5 tablets of this product, put them in a 500ml measuring flask, add appropriate amount of water, shake for about 15 minutes to dissolve lamivudine, dilute them to the scale with water, shake and filter, the appropriate amount of continuous filtrate was accurately measured, and quantitatively diluted with mobile phase to make a solution containing about 0.2mg of lamivudine per 1 ml, which was used as a sample solution. The precise amount of 20u1 was injected into the liquid chromatograph, and the chromatogram was recorded; in addition, the appropriate amount of lamivudine reference substance was accurately weighed, and the mobile phase was added for dissolution and quantitative dilution to make a solution containing about 0.2mg per 1 ml, which was determined by the same method. According to the external standard method to calculate the peak area, that is.
category
Same as lamivudine.
specification
(1)0.lg (2)0.15g (3)0.3g
storage
light shielding, sealed storage.
Last Update：2022-01-01 13:34:44
Epivir - Unsuitable object
autoimmune liver disease.
Hereditary liver diseases: such as hepatolenticular degeneration, Wilson's disease, hemochromatosis, Alpha antitrypsin deficiency, etc.
Myelosuppression: Hemoglobin <10g/L, white blood cell <4x 109/L, platelet <80x 109/L.
Last Update：2023-08-16 23:52:17
Epivir - Adverse reactions
1. A number of serious adverse events (Lactic acidosis and severe hepatomegaly with steatosis, post-treatment exacerbation of hepatitis B, pancreatitis, the appearance of Virus variants associated with decreased drug sensitivity and reduced treatment response). Clinical studies in patients with chronic hepatitis B have shown that lamivudine is well tolerated in most patients.
2. The incidence of most adverse events was similar in the lamivudine and placebo groups (see table below for details). The most common adverse events were malaise and Fatigue, respiratory tract infections, Head Pain, abdominal malaise and Abdominal Pain, Nausea, Vomit and Diarrhea.3. The following adverse reactions were also observed in 2200 Phase IV clinical studies conducted in China: 1 case of dry mouth, 1 case of systemic scarlet fever-like rash, 1 case of phosphocreatinase activity and thrombocytopenia, 1 cases of severe hepatitis in hospital. Observations in clinical activity: the following events were found during clinical use of lamivudine approval. Since these events were voluntarily reported from a population with an unknown sample size, an estimate of the incidence could not be made. These events were included because of their seriousness, frequency of reporting, possible causal relationship with lamivudine, or a combination of all these factors.
4. Internal digestive system will form stomatitis, endocrine and metabolic disorders will lead to high blood sugar, general weakness lead to anemia, and pure red blood cell regeneration will also encounter obstacles, get lymphadenopathy. In the liver and pancreas are prone to lactic acidosis and fatty degeneration, pancreatitis and other diseases, some people will have allergic reactions, such as rubella. Adverse reactions also lead to rhabdomyolysis, abnormal breathing/wheezing, even hair loss, itching, skin rash and other symptoms.
Last Update：2023-08-16 23:52:17
Epivir - Interaction
combination considerations: in a combined study, patients on lamivudine or interferon-alpha monotherapy were compared with those on interferon-alpha and lamivudine monotherapy, it was found that patients receiving α-interferon therapy had more adverse reactions, and about two thirds of all patients receiving α-interferon therapy had "influenza-like" adverse reactions. The combination of lamivudine and interferon did not improve the adverse effects of interferon-α. In conclusion, the safety profile of lamivudine 100mg once daily was similar to that of placebo, except for a slightly higher incidence of ALT elevation after treatment. Most of these patients with elevated ALT were asymptomatic.
Last Update：2023-08-16 23:52:17
Epivir - Market Development
hepatitis B mainly in China, China is the world's largest hepatitis B drug market, chronic hepatitis B Virus carriers accounted for about 34% of the world. At present, there are more than 0.1 billion chronic hepatitis B Virus carriers and more than 3000 chronic hepatitis B patients in China. At present, the annual cost of hepatitis B treatment is more than 300 billion yuan.
In China, there are two major anti-hepatitis B drugs, Chinese medicine and Western medicine, in the hepatitis B drug retail market, is playing a proprietary Chinese medicine and chemical medicine share of the battle. The proportion of Chinese patent medicines gradually shrunk, from 54.8% in 41.0% to in. Chinese patent medicines are mainly liver-protecting and liver-protecting drugs, and most of the products mainly demand "liver-protecting, liver-protecting, slow conditioning, and soothing ordinary minor discomfort", with sales leading Hugan Pian, in particular, sunflower accounted for Hugan Pian of the main market, followed by the sixth factory of Harbin, Jilin revision and Guangzhou Qixing.
Since the late 90 s of the last century, GlaxoSmithKline, Bristol-Myers Squibb, Novartis and other multinational companies have set their eyes on the Chinese market, imported liver drugs immediately entered, and quickly occupied the market dominant position. In recent years, domestic enterprises have also joined the competition, the market competition is extremely fierce, at present, domestic and imported Western medicine has gradually occupied the main domestic anti-hepatitis B drug market.
GlaxoSmithKline's lamivudine (trade name heptin) is the world's first nucleoside analog for the treatment of hepatitis B, which was approved by the US FDA in 1998. After that, Gilead's Adefovir dipivoxil (trade name) was approved in 2002. Bristol-Myers Squibb's Entecavir (bolutin) was approved in 2005 and Novartis's Telbivudine (trade name subiv) was approved in 2006.
Heptodin entered China for sale in 1999, and was included in the national medical insurance drug use in 2000, with sales revenue of 0.4 billion yuan that year. In November 2001, GlaxoSmithKline spent 1.2 billion yuan to build the world's largest production base in Suzhou and produce heptidine locally. However, today, "Heptodin" has been a great new challenge, because of the existence of a large number of Virus mutations in the clinical use of the process, the phenomenon of drug resistance.
Faced with the huge market of hepatitis B drugs, the defects of lamivudine will undoubtedly provide other drugs with the opportunity to grab the market. Bristol-Myers Squibb just saw this point and introduced entecavir into China at the end of 2005. To take full advantage, GlaxoSmithKline quickly introduced and developed an alternative to lamivudine-Adefovir dipivoxil (trade name: "He Weili").
The original intention of GlaxoSmithKline to develop adefovir (trade name "he Wei Li") is to supplement the shortage of lamivudine in order to further expand the market and strengthen its position. Because the resistance rate of Adefovir dipivoxil is much lower than that of lamivudine, the defect that lamivudine is easy to rebound due to high resistance rate is solved. At present, there are 13 Adefovir dipivoxil manufacturers in China, and more than 10 manufacturers are applying for registration. Entecavir manufacturers have Jiangsu Zhengda Tianqing Pharmaceutical, Hainan and the pharmaceutical industry, is reporting the registration of about 10 manufacturers.
In China, the market shares of lamivudine, Adefovir dipivoxil and entecavir were 24.9%, 23.7% and 15.3%, respectively. In 2009, the market shares were 24.2%, 30.0% and 32.9%, respectively. It can be seen that the market share of nucleoside antiviral drugs is increasing, among which Entecavir is the main product of the manufacturer due to its low side effects, and the growth rate is much larger than the other two varieties. Now lamivudine, entecavir, Adefovir dipivoxil has accounted for more than 60% of the domestic treatment of hepatitis B with Western medicine share.
The mechanism of action of the above two types of drugs is different, and the efficacy is also different. In the guidelines for the prevention and treatment of chronic hepatitis B of the American Association for the Study of Liver Diseases in 2007 and the treatment standard for chronic hepatitis B in 2006, it is recommended to list pegylated interferon α-2a, Adefovir dipivoxil and entecavir as the first-line treatment of hepatitis B. In China, interferon and nucleoside antiviral drugs have become the first-line treatment of hepatitis B.
Since lamivudine is the first nucleoside analog in the world for the treatment of hepatitis B, it was first introduced into China and has a five-year market gap. Therefore, lamivudine is currently the first-line drug for the treatment of hepatitis B, but in the use of found in Virus variation, drug resistance, deterioration of the disease, after stopping the disease rebound and other phenomena, after GlaxoSmithKline company in 05 launched Adefovir dipivoxil (HEV) as a second-line drug. At the same time, Bristol-Myers Squibb in the United States in 2005 introduced "Entecavir" (bolutin) to seize its market share in China. Now lamivudine and Adefovir dipivoxil, entecavir in the treatment of hepatitis B showed a "three-way" trend, occupy most of the market share. In view of the side effects of lamivudine, although lamivudine is now the first-line drug in hospitals, the market growth rate is Fatigue, which is not as fast as entecavir and Adefovir dipivoxil.
Lamivudine is currently the largest sales of first-line treatment of hepatitis B drugs, the market has a large amount, but because of its Virus mutation, drug resistance and other side effects, its growth of Fatigue, from the market perspective, is not as good as entecavir, adefovir dipivoxil and other large, especially when the entecavir patent expires (2010.11), a large number of domestic generic drugs listed, then lamivudine sales will decline year by year, thus affecting the sales of raw materials. But from the current point of view, the sales volume of this product is large, and can maintain a low growth rate for a long time.
Last Update：2023-08-16 23:49:18
Epivir - Introduction
Lamivudine is an anti-Virus drug, belonging to the nucleoside reverse transcriptase inhibitor, which can inhibit the synthesis of HIV Virus; The drug is manufactured by GlaxoSmithKline group. "Lamivudine" was first used to treat AIDS in Europe and North America in the early 1990 s. In the mid 1990 s, medical experts found that it had an inhibitory effect on Virus of the DNA of hepatitis B, in 1998, the United States Food and Drug Administration (FDA) was first approved as a treatment for hepatitis B. China's State Food and Drug Administration approved the import of the drug is mainly used as a therapeutic drug for hepatitis B. The Chinese trade name is designated as "heptin", and it was officially started to be sold in mainland China in 1999. After 10 years of clinical verification, lamivudine is the only drug that has been confirmed to delay the progression of hepatitis cirrhosis and has few side effects. At present, about 2 million of hepatitis B patients in mainland China are using it.
most hepatitis B patients will develop drug resistance after taking lamivudine for one year. New generation antivirals Adefovir dipivoxil, telbivudine, entecavir, tenofovir can solve this problem.
lamivudine is a cytidine analog that inhibits Virus of reverse transcriptase in HIV and hepatitis B. Lamivudine has antiviral activity after triphosphorylation in vivo, and the activated lamivudine also has inhibitory effect on nuclear DNA polymerase.
lamivudine was rapidly absorbed after oral administration, and its bioavailability was over 80%. Some studies have shown that it can cross the blood-brain barrier.
Last Update：2024-04-09 01:59:49
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Spot supply
Product Name: Lamivudine Visit Supplier Webpage Request for quotationCAS: 134678-17-4
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Multiple SpecificationsSpot supply
Product Name: Epivir-HBV Visit Supplier Webpage Request for quotationCAS: 134678-17-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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