Lamivudine is a new anti-hepatitis B virus drug marketed in recent years, its English name is Lamivudine, the chemical name is 2’3′-dideoxy-3′-thiocytidine (2′-3′-thiocytidine). Lamivudine, also known as 3-TC, was marketed in China under the trade name of Heptyn. Domestic and foreign randomized controlled clinical trials have shown that 100 mg of oral dose daily can significantly suppress HBV DNA level, and the HBeAg seroconversion rate increases with the prolongation of treatment time, and the HBeAg seroconversion rate is 16%, 17%, 23%, 28% and 35% after 1, 2, 3, 4 and 5 years of treatment respectively; the HBeAg seroconversion rate is generally higher for those with higher ALT level before treatment. The HBeAg seroconversion rate is also higher in those with high pre-treatment ALT levels. Long-term treatment can reduce inflammation and decrease the incidence of liver fibrosis and cirrhosis. Randomized controlled clinical trials have shown that this drug reduces the incidence of hepatic decompensation and HCC (hepatocellular carcinoma). It also improves liver function and prolongs survival in patients with decompensated cirrhosis. Results of foreign studies have shown that lamivudine has similar efficacy to adults in the treatment of chronic hepatitis B in children, with a good safety profile. In hepatitis B liver transplant patients, lamivudine is used before transplantation; after transplantation, lamivudine in combination with HBIG can significantly reduce HBV reinfection after liver transplantation, and can reduce the dose of HBIG. The chemical nature of lamivudine is a nucleoside analogue, and nucleotides are the raw materials for the synthesis of DNA and RNA, the human genetic material (DNA and RNA are actually composed of many nucleotides arranged in a long string hand in hand). Nucleoside analogs mimic the structure of nucleotides structurally, but do not have the function of nucleotides. Therefore, during DNA synthesis, nucleoside analogs can be incorporated, but they cannot synthesize a properly functioning nucleic acid strand, thus terminating the replication of the virus. Lamivudine mimics cytosine, the structure of which is different from the natural human cytosine structure, and he can only act on the virus, but not on the human body. In recent years, lamivudine has been widely accepted by doctors and patients as a new nucleoside analogue, which is the most efficacious and representative nucleoside analogue in clinical application. Its mechanism of action is inhibition of viral DNA polymutase and reverse transcriptase activities, and competitive inhibition of viral DNA strand synthesis and lengthening. Lamivudine can rapidly and effectively reduce serum HBV DNA levels, but has a high relapse rate after drug discontinuation, and long-term application can lead to viral mutation. Lamivudine is a viral inhibitor and does not clear the hepatitis B virus because it has no effect on the hepatitis B virus cccDNA, which has a half-life of about 3-4 years in the human body. If cccDNA persists, the virus will not be cleared and relapse is inevitable after stopping the drug. Therefore, in the application of lamivudine, its efficacy does not depend entirely on the drug itself, but is also closely related to the patient’s specific immune response to HBV and virulence of the virus, for patients with weak specific immune response it is difficult to achieve the purpose of virus clearance by applying lamivudine alone, but also to find ways to improve the body’s specific immune response to HBV, consider the combined application of thymidine, therapeutic vaccines and high efficiency Hepatitis B immunoglobulin, etc. Supplementary: Although lamivudine is fast-acting, the mutation rate after 1 and 2 years is high (the level of autoimmunity determines whether mutation occurs). The rate of viral resistance mutations increases with the duration of drug administration (14%, 38%, 49% and 66% in years 1, 2, 3 and 4, respectively), which limits its long-term use. In some cases, the disease worsens after the development of viral resistance mutations, and in a few cases, liver failure occurs. In addition, some patients may experience elevated HBV DNA and ALT levels after discontinuation of this drug, and some patients may even experience liver failure. Herceptin Tablets (Lamivudine) Specification 100mgX14’s, Manufacturer GlaxoSmithKline (Joint Venture). Drug Name】Lamivudine Lamivudine 【Drug Class】Antiviral drug 【Drug Alias】Heptodin Heptodin 【Molecular Composition】The chemical name of Lamivudine is (2R-cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-1H-pyrimidin-2-one. Molecular formula is C8H11N3O3S, molecular weight is 229.26. [Preparation specification] 100MG/tablet. Pharmacology and Toxicology】Lamivudine is a nucleoside antiviral drug with strong inhibitory effect on hepatitis B virus (HBV) in vitro and in experimentally infected animals. Lamivudine can be metabolized in HBV-infected cells and normal cells to produce lamivudine triphosphate, which is the active form of lamivudine and is both an inhibitor and a substrate of HBV polymerase. Lamivudine triphosphate is incorporated into the viral DNA strand to block the synthesis of viral DNA. Lamivudine triphosphate does not interfere with normal cellular deoxyribonucleoside metabolism, it has a weak inhibitory effect on mammalian DNA polymerases α and β, and has little effect on mammalian cellular DNA content. Lamivudine has no significant toxicity to mitochondrial structure, DNA content or function. The results of serum HBV DNA testing in most hepatitis B patients showed that lamivudine rapidly inhibited HBV replication and its inhibitory effect continued throughout treatment. It also reduces serum aminotransferases to normal, and long-term application can significantly improve necrotic inflammatory changes in the liver and reduce or stop the progression of liver fibrosis. Pharmacokinetics】Lamivudine is well absorbed after oral administration. Adults who take lamivudine 0.1 g orally reach the peak blood concentration Cmax 1.1-1.5 μg/mL around 1 hr, and the bioavailability is 80-85%. Concomitant administration of lamivudine with food delays Tmax by 0.25-2.5 hr and decreases Cmax by 10-40%, but bioavailability remains unchanged. The results of intravenous administration studies showed that lamivudine has a mean volume of distribution of 1.3 L/Kg and a mean systemic clearance of 0.3 L/h/kg. lamivudine is mainly (>70%) cleared via the organic cationic transport system via the kidney with a clearance half-life of 5-7 hr. Within the therapeutic dose range, the pharmacokinetics of lamivudine are linear with low plasma protein binding. In vitro studies have shown <16-36% binding to serum albumin. Lamivudine crosses the blood-brain barrier into the cerebrospinal fluid. Lamivudine is mainly excreted renally as a drug prototype, with renal excretion accounting for approximately 70% of total clearance and only 5-10% being metabolized to derivatives of trans-sulfur oxides. Renal insufficiency in patients can affect the excretion of lamivudine and its use is not recommended in patients with creatinine clearance <30 mL/min. Hepatic impairment does not affect the drug metabolism process of lamivudine. In elderly patients with decreased renal excretion function due to aging, there is no significant change in lamivudine metabolism, only when the creatinine clearance is <30 mL/min. Indications】Hepatitis B, chronic hepatitis B with hepatitis B virus replication. Adverse reactions】The product is well tolerated by patients. Common adverse reactions include upper respiratory tract infection-like symptoms, headache, nausea, body discomfort, abdominal pain and diarrhea, which are usually mild and may resolve on their own. In a comprehensive study comparing patients treated with lamivudine or alpha-interferon alone with patients treated with alpha-interferon and lamivudine in combination, more adverse reactions occurred in patients treated with alpha-interferon, with "flu-like" side effects occurring in approximately 2/3 of all patients treated with alpha-interferon. The combination of lamivudine and interferon did not improve the incidence of adverse reactions to alpha-interferon. In conclusion, the safety profile of lamivudine 100 mg once daily was similar to that of placebo, except for a slightly higher incidence of post-treatment ALT elevation. The majority of these patients with ALT elevation were asymptomatic. Dosage][Dosage and Administration] For adults, take 0.1g once daily by mouth. The optimal dose for children with chronic hepatitis B is 3 mg/kg once daily, and after the age of 12, the adult dose of 100 mg once daily should be used. [Duration of treatment]? If the patient is recovered, continue to use the drug for 3-6 months, and if the patient is still effective after review, the drug can be stopped for observation. ? Patients with pre-C zone variation cannot use HBeAg seroconversion as the efficacy assessment standard, and the course of treatment should be extended appropriately. 3-6 months after the serum HBV DNA PCR turns negative and with normal liver function can be considered after review and discontinuation for observation. Precautions] It is contraindicated for those who are allergic to lamivudine and other components of this product. The clinical condition and virological parameters of patients should be checked regularly during treatment. Hepatitis may worsen after discontinuation of this product in a small number of patients. Therefore, if the product is discontinued, the patient should be closely monitored and if the hepatitis worsens, treatment with the product should be considered again. This product is not recommended for patients with creatinine clearance <30 mL/min. Appropriate protective measures should still be taken as this product does not prevent the patient from infecting others with hepatitis B virus through sexual contact or blood-borne transmission during treatment. No information is available on the efficacy and safety of this product in patients under 16 years of age. Effects on Pregnancy and Lactation This product should not be used during pregnancy in general, except in special circumstances where the use of this product is considered by the physician to be beneficial to the pregnant woman, and should not be used in the first trimester of pregnancy. It is not necessary to stop breast-feeding while breast-feeding women are taking this product. Unless the potential risks of lamivudine to the infant outweigh the benefits to the mother. There is no information to suggest that maternal transmission of hepatitis B virus can be inhibited when this product is administered to pregnant women. Therefore, routine immunization of newborns against hepatitis B should still be administered. [Patient Selection] 1. Chronic hepatitis B in suitable treatment subjects; diagnosed with chronic hepatitis B according to the national viral hepatitis control program, of any gender, 16 years of age or older, and meeting the following criteria. ? HBeAg positive, HBV DNA positive (HBV DNA positive refers to the speckle hybridization method, not PCR positive, and HBV DNA quantitative determination can be done if conditions are available. Where there is no condition to test HBV DNA, HBeAg positivity can prevail). ? HBeAg negative, anti- HBe positive, HBV DNA positive, considering that there is a pre-C region variant is also suitable for treatment. ? ALT is higher than normal and bilirubin is less than 50μmol/L (3.0mg/dL). 2. Not suitable for treatment ? Autoimmune liver disease. ? Hereditary liver disease: such as hepatomegaly, Wilson's disease, hemochromatosis, alpha antitrypsin deficiency, etc. ? Myelosuppression: hemoglobin <10g/L, white blood cells <4x109/L, platelets <80x109/L (To date, no myelosuppressive effect of lamivudine has been found in clinical studies. Side effects of lamivudine The toxic side effects of drugs belonging to the first generation of pro-nucleoside analogues are relatively high; for example, ganciclovir has mild to moderate toxicity to the bone marrow and kidney. The second-generation nucleoside analogs, on the other hand, are relatively less toxic. Transient elevations of amylase and lipase have been reported in 10% of patients taking lamivudine; mutations in HBV viral DNA polymerase (commonly referred to as YMDD mutations) may occur after long-term use, generally in patients treated for more than 6 months. However, studies have also concluded that continued application of lamivudine in that setting is still clinically effective. Lamivudine was well tolerated in all studied patient populations. In phase II and III clinical trials, there was no increase in the incidence of adverse reactions associated with an increase in total dose and an increase in the duration of therapy. Discontinuation of lamivudine treatment due to adverse reactions was rare in clinical trials. Lamivudine should be used with caution Lamivudine, a new nucleoside antiviral drug, has been widely used worldwide for the antiviral treatment of patients with hepatitis B virus (HB V) and AIDS virus (HIV) infection since its introduction in 1991. Early clinical safety studies have concluded that lamivudine is safe and non-toxic, without "triptogenic (teratogenic, carcinogenic and mutagenic) effects", and that the adverse effects are only mild headache, transient drowsiness, nausea, fatigue and discomfort in the liver area, etc. The incidence is low and patients can adapt and tolerate it quickly. However, with the increasing prevalence of clinical application, the incidence and frequency of adverse reactions have been increasing year by year. The following adverse reactions have been identified: Allergic reactions: Lamivudine can cause more serious allergic reactions, especially in first-time treatment recipients. In a case reported abroad, a 49-year-old male with HI V infection took 150 mg of lamivudine for the first time. Half an hour later, he suddenly felt itchy skin, followed by urticaria in many parts of the body, tightness in the throat, obstruction, dysphagia and dyspnea, numbness and immobility of the tongue, and slurred speech. Ten minutes later, he developed dyspnea, full lung rales, dizziness, and cold extremities, and his blood pressure was measured at 70/40 mmHg. He was admitted to the intensive care unit and was resuscitated for several hours with antianaphylaxis before he was brought to safety. The patient had used antiviral drugs such as zidovudine and acyclovir in the past, but had not experienced a similar reaction. This severe allergic reaction often occurs in atopic drug-takers and occurs suddenly at the first dose without any aura before the onset, and after the onset may present with severe laryngeal angioneurotic edema, which may be fatal without timely resuscitation. Stop rebound and liver failure: Because this agent only inhibits the DNA polymerase activity of sensitive viruses and slows down the replication rate of viruses and reduces the serum content, but cannot safely remove viruses from the body, so rebound is likely to occur after stopping the drug if the course of treatment is too short (<6 months), not only does liver function abnormalities occur, but also the viral replication index changes from negative to positive, and sometimes the viral content is even much higher than the level before treatment. Some people are not immune even after 1 to 1.5 years of drug use. The clinical manifestation is that the hepatitis recurs after stopping the medication. Some people who were originally hepatitis B virus (HBV) carriers with normal liver function suddenly stop using the medication, but thus induce liver failure. There was a case of a 29-year-old male patient with chronic hepatitis B. He took 100 mg of lamivudine daily without other adverse effects, and after two weeks of use, his HBV-DNA turned negative and his hepatitis B e antigen (HBeA g) dropped to a very low level. The liver function returned to normal by week 16, and the patient was happy to stop the drug without permission. However, after only 4 weeks, liver function rebounded, starting with nausea, aversion to oil, yellow urine, elevated serum aminotransferases, which exceeded 100 times the normal value after 4 months, jaundice, a 50% reduction in coagulation factors, and a positive viral marker, which was only turned to safety after multiple resuscitations. According to the latest report from Japan, among 194 patients who applied lamivudine, 6 cases of hepatitis B disease worsened when the drug was suddenly stopped, and one of them died of liver failure 3 months later. In addition, HBV mutations and drug resistance that occur during lamivudine administration can also worsen clinical symptoms and individual patients can develop ascites. Nail fungus: In recent years, the UK reported 12 cases of nail fungus in AIDS patients after drug administration, 11 of which were men, mostly after 3 months of treatment. After topical treatment with imidazole antifungal drugs, 5 cases were cured after 1 month, while the other 7 cases had recurrent attacks and persisted. Fat metabolism disorders: Foreign reports have shown that the combination of lamivudine and protease inhibitors in the treatment of HIV infection can cause fat metabolism disorders. 4 cases treated with indinavir or zidovudine had severe cardiovascular disease 3 weeks to 16 months after treatment, including 3 cases with acute myocardial infarction and 1 case with transient recurrent myocardial ischemia. Blood triglyceride and cholesterol levels were found to be elevated. In a few cases, abnormal fat distribution can also occur. A 38-year-old male with AIDS who had been co-administered stavudine for 6 months gained 3 kg of weight, and 9 months later had abnormal thickening and accumulation of fat in the neck and back, with a buffalo back appearance. Causes hemophilia bleeding: Newly reported abroad, two cases of hemophilia patients who applied lamivudine combined with indinavir and zidovudine against HIV developed frequent spontaneous bleeding from joints and digestive tract after 6 months and returned to normal only after two weeks of discontinuation of the drug. Effects on newborns: In the United States, it was found that in a 30-year-old female HIV-infected patient who remained on lamivudine and zalcitabine during pregnancy, the infant was born with severe anemia and developed heart failure. In a group of 194 cases in France who applied lamivudine plus zidovudine to prevent mother-to-child transmission of HIV, two infants also developed a rare type of mitochondrial DNA gene damage and died within 1 year after birth. The above is the latest information on the adverse reactions of lamivudine application reported in the domestic and international literature in recent years, some of them are rare, but once they occur, the consequences are often quite serious, so the clinic should be strictly alert. When using drugs should be properly selected and screened, fully grasp the application indications, not blindly abuse.