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Isoniazid Tablets Instructions
Please read the instruction manual carefully and use under the guidance of your physician
WARNING: Serious and even fatal drug-related liver injury has been reported with isoniazid treatment, which may occur even months after treatment ends. Daily alcohol consumption increases the risk of drug-related liver injury from isoniazid, and there are no accurate data on the mortality rate of drug-related liver injury from isoniazid. Therefore, patients taking isoniazid should be closely monitored and followed monthly.
Drug-related liver injury usually occurs in the first 3 months of isoniazid therapy. With continued medication, enzyme levels usually return to normal, but some patients develop progressive liver impairment. High risk factors for drug-related liver injury are daily alcohol consumption, chronic liver disease, and injection drug use. A recent study has shown that female patients taking isoniazid are at increased risk for fatal liver injury; women may also be at increased risk for drug-related liver injury after childbirth. Therefore, closer monitoring, such as increased laboratory testing, should be performed in these populations. Discontinuation of isoniazid should be considered if abnormal liver function parameters exceed 3 to 5 times the upper limit of normal values. Liver function tests should not be used as a substitute for regular monthly clinical assessments, without which adverse effects during treatment cannot be assessed on time. Patients should be instructed to immediately report signs or symptoms associated with liver injury or other adverse reactions, including any of the following: unexplained anorexia, nausea, vomiting, dark urine, jaundice, skin rash, persistent abnormal sensation in the hands and feet, persistent fatigue, malaise, or fever and/or abdominal tenderness lasting more than 3 days, especially if right upper abdominal discomfort is present. If a patient develops any of these symptoms or has test results suggestive of liver impairment, isoniazid should be discontinued immediately, and studies suggest that continued use of the drug in such cases can cause more severe liver injury.
Tuberculosis patients who develop isoniazid-associated liver injury can be treated with other anti-tuberculosis drugs instead. If isoniazid is to be reintroduced, it should not be reintroduced until symptoms have disappeared and laboratory abnormalities have returned to normal. When patients are reintroduced to isoniazid therapy, the starting dose should be as low as possible, followed by a gradual increase in dose and immediate discontinuation if there is any sign of recurrence of liver disease.
Patients with acute liver disease should delay prophylactic therapy.
[Drug Name].
Generic Name: Isoniazid Tablets
English Name: Isoniazid Tablets
Hanyu Pinyin: Yiyanjing Pian
[Ingredients
The main ingredient of this product is isoniazid.
Chemical name: 4-pyridinecarbohydrazide
Chemical structure formula.
Molecular Formula: C6H7N3O
Molecular weight: 137.14
[Properties] This product is a white or off-white tablet with an indentation in the middle of one side.
[Indications
To ensure the effectiveness of this and other antibacterial drugs and to reduce the occurrence of drug resistance, the antibacterial drug regimen may be changed or adjusted based on sputum culture and drug sensitivity results. In the absence of such data, treatment is given based on local epidemiologic and drug-sensitivity experience.
1. This product is indicated in combination with other anti-tuberculosis drugs for the treatment of all types of tuberculosis that are sensitive to isoniazid.
2. This product can be used for the prevention of tuberculosis as indicated below (Mycobacterium tuberculosis skin test (PPD) criteria in parentheses).
① Human immunodeficiency virus (HIV) infected (≥5mm) and those suspected of being HIV infected (not yet certain of infection with Prophylaxis for HIV-infected patients should be continued for at least 12 months.
② Persons who have had close contact (≥10mm) with a patient newly diagnosed with infectious TB.
③ Patients with recent PPD conversion or progression: tuberculin skin test results (≥10-15mm increase within 2 years). All infants and children younger than 5 years of age with skin test results>10 mm were included.
④ Patients (≥10mm) with abnormal chest radiographs suggesting that the lungs may have healed from Mycobacterium tuberculosis causing fibrotic lesions. Patients with healed TB fibrosis or silicosis may be considered for prophylactic therapy with isoniazid for 12 months or a combination of isoniazid and rifampin for 4 months.
⑤HIV-negative (≥10mm)for intravenous drug users.
3, Based on clinical experience in China, this product can also be used in combination with other anti-tuberculosis drugs for other Mycobacterium infections, but there is not yet sufficient data from clinical studies to support this.
[Specification] 0.1g
[dosage]
1.
Isoniazid should be used in combination with other effective anti-tuberculosis drugs. Drug susceptibility testing should be performed in all patients with a recent diagnosis of TB disease. If Mycobacterium tuberculosis has become resistant to this drug, treatment should be switched to a sensitive drug.
Common oral dose (depending on the purpose of treatment)
Adults
Daily dose of 5 mg/kg in a single dose, with a maximum daily dose of 300 mg/day.
Or 15mg/kg twice or three times a week at a maximum daily dose of 900mg/day.
Children
Daily dose of 10mg/kg to 15mg/kg in a single dose, with a maximum daily dose of 300mg/day.
Or take 20mg/kg to 40mg/kg twice or three times a week at a maximum daily dose of 900mg/day.
Patients with tuberculosis who are not infected with HIV
There are three initial treatment regimens available for children and adults with tuberculosis as follows.
Option 1: Daily maintenance treatment with a combination of isoniazid, rifampin, and pyrazinamide for 8 weeks, followed by 16 weeks of maintenance treatment with a combination of isoniazid and rifampin daily or 2 to 3 times per week. The initial regimen should be combined with ethambutol or streptomycin until the patient is confirmed to be sensitive to isoniazid and rifampin. If the relative prevalence of isoniazid-resistant Mycobacterium tuberculosis in the community is less than or equal to 4%, a fourth drug may be added optionally.
Option 2: Daily maintenance therapy with a combination of isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol for 2 weeks, followed by adjustment of dosing frequency to twice weekly maintenance therapy for 6 weeks, and final maintenance therapy with a combination of isoniazid and rifampin administered twice weekly for 16 weeks.
Option 3: Combined isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin maintenance therapy for 6 months, administered three times a week.
Direct face-to-face supervised therapy (see DOT for details) is recommended for all treatment options.
The above regimens are only indicated for TB that is sensitive to standard anti-TB drugs. Ethambutol is not recommended for children who cannot be monitored for changes in visual acuity.
Tuberculosis patients with HIV infection
When immune function is impaired, anti-tuberculosis treatment in TB patients may be less effective than in immunocompetent individuals, and therefore the anti-tuberculosis regimen for such patients should be individualized. Such patients may have poor drug uptake and require monitoring of blood levels, especially in patients with advanced HIV, to prevent the emergence of multidrug-resistant tuberculosis (MDR-TB).
Patients with extrapulmonary TB
The basic principles of TB treatment also apply to extrapulmonary TB disease. Cornual tuberculosis, bone/joint tuberculosis, and tuberculous meningitis should receive treatment for at least 12 months.
Extrapulmonary TB is evaluated for efficacy primarily on the basis of clinical and imaging findings.
In contrast to pulmonary tuberculosis, extrapulmonary tuberculosis often requires adjunctive treatment with surgery and corticosteroids. For example, surgical biopsy to clarify the diagnosis, surgical debridement of the thickened pericardium, and release of the associated spinal cord compression. Studies have shown that early application of corticosteroids can help prevent the development of tuberculous pericarditis into constrictive pericarditis and reduce the neurological sequelae of all stages of tuberculous meningitis.
Patients with TB combined with pregnancy
The treatment regimen for pregnant patients must be adjusted and it is recommended to consult a TB specialist to develop the appropriate treatment regimen at different stages of pregnancy.
Treatment of patients with multidrug-resistant tuberculosis (MDR-TB)
Patients with multidrug-resistant TB (i.e., resistant to at least isoniazid and rifampin) are difficult to treat. Individualized treatment must be implemented based on the results of drug susceptibility testing. In such cases, consultation with a TB specialist is recommended to develop a treatment plan.
Direct face-to-face supervised therapy (DOT)
The main cause of drug-resistant TB is patient non-compliance. The use of DOT ensures patient compliance with drug therapy. dOT is the observation of patients taking anti-tuberculosis drugs by a health care provider or other responsible person. dOT can be used in a variety of treatment regimens and is recommended for all patients.
2. Preventive treatment of tuberculosis
Positive TB must be ruled out or active TB ruled out by chest imaging before prophylaxis with isoniazid can be used. If extrapulmonary TB is suspected, appropriate evaluation should be performed first.
Adults over 30 kg: 300 mg daily in a single dose.
Infants and children: 10 mg/kg daily (maximum daily dose 300 mg). In cases where compliance with daily prophylaxis cannot be ensured, a DOT regimen of 20-30 mg/kg (maximum dose 900 mg) taken twice weekly is recommended.
Since relapse rates are higher when treatment is stopped prematurely, a full course of isoniazid is an important part of the treatment regimen. Changes in the treatment regimen may be necessary when resistant organisms emerge during treatment.
Concomitant administration of vitamin B6 is recommended for patients who are malnourished and at risk for neuropathy (e.g., alcoholics and diabetics).
[Adverse effects
The most common adverse reactions are neurological reactions and liver function impairment.
Nervous system: The most common reaction was peripheral neuropathy. The incidence of this adverse reaction is dose-dependent and is most common in patients with malnutrition and at risk for neuropathy (e.g., alcoholics and diabetics), with a common early reaction of abnormal sensation in the hands and feet and a higher incidence in “slow acetylators”. Rare neurotoxic side effects at regular doses include convulsions, toxic encephalopathy, optic neuritis, optic atrophy, memory impairment, and toxic psychosis.
Hepatic system: Elevated serum transaminases, elevated serum bilirubin, jaundice, and occasionally severe hepatic impairment or even fatal hepatitis. Common prodromal symptoms of hepatitis include anorexia, nausea, vomiting, fatigue, malaise, and malaise. 10% to 20% of patients taking isoniazid develop a transient, mild elevation of serum transaminase levels, an abnormality that usually occurs in the first 1 to 3 months of treatment but may occur at any time during treatment. In most cases, liver enzyme levels return to normal and therefore, discontinuation of the drug is usually not required in the case of mild serum aminotransferase elevations. However, in some cases, liver damage can progress progressively. Discontinuation of the drug is strongly recommended if the AST value exceeds 3 to 5 times the upper limit of normal. The incidence of liver injury increases with age.
Hematologic system: Granulocyte deficiency, hemolysis, iron granulocyte or aplastic anemia, thrombocytopenia, and eosinophilia. Cellulite.
Hypersensitivity reactions: fever, rash (measles, maculopapular rash, purpura or exfoliative dermatitis), lymphadenopathy and vasculitis, toxic epidermal necrolysis relaxation, drug rash with eosinophilia and systemic symptoms The drug rash (DRESS).
Metabolic and endocrine system: vitamin B6 deficiency, pellagra, hyperglycemia, metabolic acidosis, and gynecomastia.
Other: rheumatic syndrome and systemic lupus erythematosus-like syndrome.
This product is contraindicated in patients with severe hypersensitivity reactions to isoniazid, including pharmacologic hepatitis; prior isoniazid-related liver injury; severe adverse reactions to isoniazid e.g., pharmacogenic fever, chills, arthritis; acute liver disease of any type.
[Precautions].
1. General Precautions
(1) If hypersensitivity reactions occur with this product, discontinue immediately and evaluate. If continued use of isoniazid is required, it should not be resumed until symptoms have resolved. When a patient restarts isoniazid therapy, the starting dose should be as low as possible, followed by a gradual increase in the dose administered and immediate discontinuation if there is any sign of recurrence of hypersensitivity reactions.
(2) The following patients should be closely monitored when administering isoniazid.
1) Patients who consume alcohol daily. Patients who drink alcohol daily are more likely to develop isoniazid-related liver injury.
2) Patients with chronic active hepatitis or severe renal insufficiency.
3) Patients who require long-term use of other medications during treatment.
4) Patients with a previous history of isoniazid withdrawal.
5) Patients with peripheral neuropathy or at risk for neuropathy .
6) Pregnancy.
7) Injecting drug users.
8) A small number of female patients, especially postpartum women.
9) HIV-positive individuals.
(3) Isoniazid can also be used for the treatment of other Mycobacterium infections, depending on the strain identification and drug sensitivity.
Treatment regimens should be developed based on the results of strain identification and drug sensitivity testing.
2. Laboratory tests
Isoniazid has a high incidence of drug-related liver injury in some specific populations, including daily alcohol consumption, chronic active hepatitis, injection drug use, and a small number of female patients, especially postpartum women. The above patients should have their liver function checked regularly before and during treatment. Liver function monitoring should be performed monthly during prophylactic treatment, and more frequently if necessary. If transaminase levels exceed the upper limit of normal by 3 to 5 times, the drug should be suspended.
[For Pregnant and Lactating Women
(1) Embryonic death was observed in rats and rabbits when isoniazid was given orally during gestation. Reproductive toxicity studies in mice, rats and rabbits showed no teratogenic effects of isoniazid. There are no adequate and reliable clinical studies in women during pregnancy. When a pregnant woman is in active TB infection, the benefit of maternal treatment with isoniazid will outweigh the risk to the fetus, and therefore treatment with isoniazid is recommended. When using isoniazid for prophylaxis, the potential benefits of prophylaxis should be weighed against the potential risks to the fetus. Prophylactic therapy should generally be initiated after delivery to reduce the risk of fetal exposure to isoniazid; isoniazid levels in breast milk are low enough not to cause harm to the newborn. Isoniazid crosses the placental barrier, so newborns exposed to isoniazid through their mothers should be closely monitored for adverse effects.
(2) Small amounts of isoniazid in breast milk are not toxic to newborns; therefore, breastfeeding can continue while taking isoniazid. The amount of isoniazid in breast milk is very low and not sufficient to have a preventive or therapeutic effect on the nursing infant.
[Pediatric Dosage
Use strictly in accordance with pediatric dosage.
[For Elderly].
The incidence of drug-related liver injury is increased in elderly patients.
[Drug Interactions
Food: Isoniazid should not be taken with food. Studies have shown that the bioavailability of isoniazid is significantly reduced when it is taken with food. Patients receiving isoniazid therapy should avoid foods rich in tyramine and histamine. Because isoniazid mildly inhibits monoamine oxidase activity, interactions with tyramine-containing foods (cheese, red wine) may occur. Isoniazid also inhibits diamine oxidase, and patients are susceptible to symptoms of histamine toxicity (e.g., headache, sweating, palpitations, flushing, and hypotension) after consuming histamine-rich foods (e.g., bonito, tuna, other tropical fish) while taking the drug.
Alcohol consumption: Daily consumption of alcohol while taking isoniazid predisposes to hepatotoxic reactions induced by this product and accelerates the metabolism of isoniazid, so the dose of isoniazid needs to be adjusted and signs of hepatotoxicity closely monitored. Patients should be advised to avoid alcohol and alcoholic beverages while taking the drug.
Acetaminophen: Severe acetaminophen toxicity has been reported in patients taking isoniazid. Studies have found that this toxicity may be caused by an unidentified interaction between isoniazid and acetaminophen, and a molecular mechanism for this interaction has been proposed. However, the current study shows that isoniazid induces the activity of the multifunctional oxidase P-450IIE1 in the liver, which converts acetaminophen into a toxic metabolite. It was shown that acetaminophen hepatotoxicity was increased in rats pretreated with isoniazid.
Carbamazepine: Isoniazid can inhibit the metabolism of antiepileptic drugs and increase their blood levels. Signs and symptoms associated with toxic reactions to carbamazepine should be monitored closely during dosing, and the carbamazepine dose should be adjusted accordingly.
Phenytoin: Isoniazid can lead to increased blood levels of phenytoin. To avoid phenytoin toxicity, the dose of anticonvulsants should be adjusted appropriately.
Sodium valproate: A recent case study suggests that blood levels of valproic acid may be increased when combined with isoniazid. Blood levels of valproic acid should be monitored and the dose of valproate adjusted appropriately when isoniazid and sodium valproate are combined.
Ketoconazole: There may be potential interactions between antifungal agents such as ketoconazole and isoniazid. Studies have shown that when isoniazid was taken with rifampin for 5 months, the AUC of ketoconazole was reduced by 88%.
Miconazole: Isoniazid should not be combined with miconazole because it can reduce the latter’s blood levels.
Itraconazole: It has been reported that isoniazid has a hepatic drug metabolizing enzyme-inducing effect, which promotes the metabolism of itraconazole and leads to a decrease in its blood concentration.
Theophylline: A recent study suggests that the combined use of isoniazid and theophylline may result in increased blood levels of theophylline and, in some cases, a slight decrease in isoniazid clearance. Because of the narrow therapeutic range of theophylline, theophylline blood levels should be monitored closely and the dose of theophylline adjusted appropriately.
Aluminium-containing acidophiles: Aluminium-containing acidophiles can delay and reduce the absorption of oral isoniazid and decrease blood levels, so avoid taking them together or take isoniazid at least 1 hour before taking an oral acidophilus. .
Anticoagulants: Anticoagulants (e.g., coumarin or indandione derivatives) have enhanced anticoagulant effects due to inhibition of enzymatic metabolism of anticoagulants when administered concomitantly with isoniazid.
Anti-tuberculosis drugs: Isoniazid can increase CNS adverse effects (e.g., dizziness or drowsiness) when taken with cycloserine, requiring dose adjustment and close observation for signs of CNS toxicity, especially Patients who are working with high sensitivity. The risk of hepatotoxicity is increased when isoniazid is combined with rifampin and ethionamide, especially in those with pre-existing hepatic impairment or rapid acetylation of isoniazid, and should be followed closely for signs of hepatotoxicity during the first 3 months of treatment.
Adrenocorticotropic hormone: especially when combined with prednisolone, may increase the metabolism and excretion of isoniazid in the liver, resulting in a decrease in the latter’s blood level and affecting the efficacy, especially in fast acetylators. The dose should be adjusted appropriately.
Alfentanil: When combined with alfentanil, the effects of alfentanil can be prolonged because isoniazid is a hepatic drug enzyme inhibitor.
Disulfiram: Combination with disulfiram (disulfiram) enhances its central nervous system effects, producing vertigo, motor incoordination, irritability, and insomnia; combination with anflurane may Increase the formation of nephrotoxic inorganic fluoride metabolites.
[Drug overdose
Signs and symptoms: Symptoms appear within 30 min to 3 h after an overdose of isoniazid. Early symptoms include nausea, vomiting, dizziness, slurred speech, blurred vision, and hallucinations (including bright colors and strange patterns). In severe overdose, respiratory distress and central nervous system depression may occur, which can progress rapidly from trance to deep coma, accompanied by severe intractable seizures. Typical laboratory test abnormalities following isoniazid poisoning include severe metabolic acidosis, ketonuria, and hyperglycemia.
Treatment: Untreated or untreated isoniazid overdoses of 80 mg/kg to 150 mg/kg can lead to neurotoxicity and even death, but most patients heal well within a few hours of overdose with appropriate treatment. However, most patients heal well with appropriate treatment within hours of overdose.
For asymptomatic patients: activated charcoal may reduce the absorption of isoniazid in the gastrointestinal tract. Gastric lavage should also be performed in asymptomatic patients. Care should be taken to keep the patient breathing well when taking the above treatment measures. Patients who acutely ingest >80 mg/kg isoniazid should receive an intravenous equivalent dose (g) of vitamin B6. If the dose of isoniazid ingestion is unclear, adults should receive 5 g of vitamin B6 intravenously over 30-60 min, and children can receive 80 mg/kg of vitamin B6 intravenously.
For symptomatic patients: Treatment of seizures and reduction of isoniazid absorption, adequate ventilation, maintenance of cardiac output, and airway protection should be ensured. If the ingested dose of isoniazid is known, treatment with a slow intravenous push of equal dose (g) of vitamin B6 over 3 to 5 minutes should be the first step. If the ingested dose of isoniazid is unknown, 5 g of vitamin B6 is given intravenously in adults and 80 mg/kg of vitamin B6 is given intravenously in pediatric patients. vitamin B6 may be repeated as needed if seizures continue. very few patients require more than 10 g of vitamin B6. the maximum safe dose of vitamin B6 in the treatment of isoniazid poisoning is not known. If the patient is ineffective with vitamin B6, diazepam may be used; however, phenytoin sodium should be used with caution because isoniazid interferes with phenytoin sodium metabolism.
General: Collect patient Blood samples, immediate blood gas analysis, testing of electrolyte levels, BUN, blood glucose, etc.; preparation of blood for appropriate plasma and blood type cross-matching in preparation for possible hemodialysis.
Rapid control of metabolic acidosis: Patients with a degree of isoniazid toxicity may be hyperventilating. Administration of sodium bicarbonate at this time can cause hypercapnia. If the patient is respiratory insufficiency, ventilation must be carefully monitored by monitoring blood carbon dioxide levels, and mechanical ventilation support must be given.
[Pharmacology and Toxicology].
Pharmacological effects
Mechanism
Isoniazid inhibits the synthesis of mycolic acid, a key component of the bacterial cell wall. At therapeutic concentrations, isoniazid was bactericidal against both intracellular and extracellular Mycobacterium tuberculosis in the growth and reproduction phase.
Resistance
Resistance to isoniazid is usually due to genetic mutations in katG, inhA, kasA, and ahpC. When isoniazid monotherapy is administered, Mycobacterium tuberculosis quickly develops resistance.
Microbiological testing
Two standardized in vitro drug susceptibility assays are available for testing the susceptibility of isoniazid to Mycobacterium tuberculosis. The agar ratio method (CLSI, M24-A2): Middlebrook 7H10 or 7H11 medium is utilized and final concentrations of 0.2 µg/mL and 1.0 µg/mL isoniazid, respectively, are added; Mycobacterium tuberculosis is diluted 10-2 to 10-4 times with the Mackenzie turbidity standard 0.5 to 1.0. MIC 99 was calculated by comparing the amount of bacteria grown in medium containing the drug with control medium. Growth of Bifidobacterium spp. in the presence of the drug ≥1% compared with the control indicates drug resistance.
Radiation broth method: The BACTEC 460 instrument was used to compare the growth index (GI) of drug-free media with media containing 0.2 µg/mL and 1.0 µg/mL of isoniazid . This test requires strict adherence to the manufacturer’s sample handling methods and data resolution.
Mycobacterium tuberculosis MIC 99 values ≤ 0.2 µg/mL are considered sensitive to isoniazid. Susceptibility test results obtained by the two methods described above cannot be compared unless equivalent drug concentrations are assessed.
The clinical relevance of in vitro susceptibility to Mycobacterium spp. other than Mycobacterium tuberculosis using the BACTEC or proportional methods has not been determined.
Toxicological studies
Genotoxicity: Isoniazid is weakly mutagenic in unmetabolically activated strains of Salmonella typhimurium (Ames test) TA 100 and TA 1535.
Reproductive toxicity: Isoniazid administered orally during gestation in rats and rabbits can cause embryonic death. No teratogenic effects of isoniazid were seen in reproductive toxicity studies in mice, rats, and rabbits.
Carcinogenicity: Isoniazid induced lung tumors in several mouse strains. Isoniazid has not been shown to be carcinogenic in humans. (Note: A case of mesothelioma has been diagnosed in a child prenatally exposed to isoniazid who had no other apparent carcinogenic risk factors).
The blood concentration peaks 1-2 hours after oral administration and decreases to 50% or less within 6 hours. Isoniazid readily diffuses into all body fluids (cerebrospinal fluid, pleural fluid, and ascites), tissues, organs, and excretions (saliva, sputum, and feces), and also crosses the placental barrier and enters breast milk at the same concentration as the blood drug concentration. Within 24 hours, 50%-70% of isoniazid is excreted through the urine.
Isoniazid is primarily metabolized by acetylation and dehydration reactions. The rate of acetylation is genetically determined, with approximately 50% of blacks and whites being “slow inactivators” and the rest being “fast inactivators”; most Eskimos and Orientals are “fast inactivators.
The rate of acetylation does not significantly alter the effectiveness of isoniazid, but slow acetylation may lead to higher blood levels and therefore increased toxic effects.
Pyridoxine (vitamin B6) deficiency sometimes occurs in adults on high doses of isoniazid, possibly due to its competitive binding to pyridoxal phosphate on deoxynivalenolase.
[Storage] Store in a dry place, protected from light and sealed.
[Packaging] High density polyethylene bottle for oral solid medication; 100 tablets/bottle.
[Expiration date] 18 months
[Execution Standard
[Approval Number]
State Pharmacopoeia H12020232
[Drug Marketing Authorization Holder
Name: Tianjin Lisheng Pharmaceutical Co.
Registered Address: No. 16, Saeda North Road, Xiqing Economic Development Zone, Tianjin
[Manufacturer
Company Name: Tianjin Lisheng Pharmaceutical Co.
Manufacturing Address: No. 16, Saeda North Road, Xiqing Economic Development Zone, Tianjin
Postal Code: 300385
Tel: 022-27366012
Fax Number: 022-27364239
Website: www.lishengpharma.com