Approval date: August 15, 2011
Modification date: 2013
Month
Date
Elamod Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic Name: Eramod Tablets
Trade Name: Edesin®
English Name: Iguratimod Tablets
Hanyu Pinyin: Ailamode Pian
Ingredients
The active ingredient of this product is Ailamode.
Chemical name: N-[3-(formyl)-4-oxo-6-phenoxy-4H-1-benzopyran-7-yl]-methanesulfonamide
Chemical structure formula.
Molecular formula: C17H14N2O6S
Molecular weight：374.37
Properties]: This product is white or off-white tablet.
Indications】Active rheumatoid arthritis.
Specification】25mg.
Dosage]
Take orally. Take 25mg (1 tablet) once after meals, twice a day, once in the morning and once in the evening.
Adverse reactions
1. In the domestic phase II and III clinical trials, 518 patients with active rheumatoid arthritis used this product.
In the phase II clinical trial, 192 patients with active rheumatoid arthritis used this product. In the phase II clinical trial.
Common adverse drug reactions (>1/100, <1/10) were mainly upper abdominal discomfort, elevated aminotransferase, nausea, nausea, rash or pruritus, headache, dizziness, decreased white blood cells, tinnitus or hearing loss, fatigue, abdominal distention, lower extremity edema, palpitations, decreased hemoglobin, insomnia, excessive sweating, vomiting, chest tightness, elevated platelets, decreased platelets, abnormal electrocardiogram, chills, drowsiness. poor mental health, swelling of hands, menstrual disorders, gum bleeding, facial edema.
In phase III clinical trials, 326 patients with active rheumatoid arthritis were treated with this product. In the phase III clinical trial.
Very common adverse drug reactions (>1/10) were mainly aminotransferase elevations.
common adverse drug reactions (>1/100, <1/10) were mainly leukopenia, gastric discomfort, dyspepsia, rash, epigastric discomfort, nausea, bloating, gastroparesis, thrombocytopenia, acid reflux, abdominal pain, gastric distention, blurred vision, pruritus, duodenitis, gastritis, fecal occult blood, alopecia, insomnia, ECG abnormalities, menstrual disorders, and decreased hemoglobin.
Less common adverse drug reactions (>1/1000, <1/100) were mainly diarrhea, dyspepsia, gastric ulcer, reflux esophagitis, duodenal ulcer, gastric sinus bleeding, vomiting, fever, cough, dry mouth, mouth ulcer, facial edema, skin edema, fatigue, chest tightness, chest pain, positive urine protein, elevated total bilirubin, flu-like symptoms, upper respiratory tract infection, and poxiform gastritis.
Most of the above adverse reactions are relieved or disappeared after discontinuation of the drug.
2. According to the literature, the following adverse reactions were reported in clinical trials in Japan.
When this product is used alone
In the clinical trial of this product alone in Japan, a total of 798 patients used this product. The major adverse reactions were elevation of alanine amino-converting enzyme (ALT) in 148 cases (18.55%), glutamate amino-converting enzyme (AST) in 132 cases (16.54%), γ-GTP in 86 cases (15.72% out of 547 cases), ALP in 119 cases (14.91%), NAG in 72 cases (9.02%), urinary β2 micro (7.39%), total bile acids (5.71%, out of 385 cases), abdominal pain (44 cases, 5.51%), and skin rash (41 cases, 5.14%).
In combination with methotrexate (6 to 8 mg/week)
In a clinical trial of the combination with methotrexate (6~8mg/week) in Japan, a total of 232 patients used this product. The main adverse reactions were elevated AST in 27 cases (11.64%), elevated ALT in 27 cases (11.64%), lymphopenia in 21 cases (9.05%), nasopharyngitis in 19 cases (8.19%), decreased blood iron in 19 cases (8.19%), elevated γ-GTP in 16 cases (6.90%) 16 cases (6.90%), and elevated urinary β2 microglobulin in 13 cases ( 5.60%), etc.
(1) Major adverse reactions
(1) Liver dysfunction (0.49%), jaundice (0.10%): Since liver dysfunction and jaundice with elevated AST and ALT may occur, measures such as regular checkups should be taken for adequate observation, and when abnormalities are detected, measures such as discontinuation of medication should be taken for proper management.
(2) Various types of hemocytopenia and leukopenia (both 0.10%): Because of the possibility of various types of hemocytopenia and leukopenia, measures such as regular checkups should be taken for adequate observation, and when abnormalities are found, measures such as discontinuation of medication should be taken for proper management.
(3) Peptic ulcer (0.68%): Since peptic ulcers thought to be caused by cyclooxygenase inhibition may occur, when digestive symptoms such as blood in the stool occur, the drug should be discontinued and handled appropriately.
(4) Interstitial pneumonia (0.29%): Because of the possibility of interstitial pneumonia, when symptoms such as fever, cough and dyspnea occur, chest X-ray, etc. should be performed immediately, and measures such as administration of adrenocorticotropic hormones should be taken for proper management while discontinuing medication.
(5) Infection (0.19%): Because of the possibility of sepsis, septic chest and other infections, adequate observation should be made, and when abnormalities are found, the drug should be discontinued and handled appropriately.
(2) Other adverse reactions
When the following adverse reactions occur, proper treatment should be carried out according to the symptoms.
Type 10~20%1~10%0.5~1%0.5%Hepatic AST increase, ALT increase, ALP increase, γ-GTP increaseTotal bile acid increaseBilirubin increase in bloodUrobilinogen increase in urineBlood-hemoglobin decrease, erythrocyte pressure product decrease, neutrophilia, lymphocytopenia, leukocytosis, leukopenia Erythropoietic anemia thrombocytopenia, thrombocytosis, basophilia, neutrophilia, neutropenia, monocytosis, abnormal lymphocyte morphology digestive organs – abdominal pain, stomatitis, positive fecal occult blood, nausea, abdominal discomfort, diarrhea, peptic ulcer gastritis, dyspepsia, vomiting, loss of appetite, labyrinthitis constipation, abdominal fullness, tongue inflammation, esophagitis, upper abdominal discomfort, gastroenteritis, gastrointestinal dysfunction, periodontitis kidney – elevated NGA, elevated β2 microglobulin in urine, elevated urea in blood, decreased β2 microglobulin in blood, positive protein in urine, positive red blood cells in urine, positive white blood cells in urine, urinary tubular pattern, positive urine sedimentation, elevated creatinine in blood pyelonephritis, urinary frequency allergy symptoms Note ) – rash, pruritus eczema, urticaria erythema, photoallergic reactions metabolic abnormalities – decreased blood iron, elevated BNP decreased blood cholinesterase, decreased total protein positive urine glucose, decreased blood albumin, diminished total iron binding capacity, enhanced unsaturated iron binding capacity psychoneurological – -dizziness headache, insomnia, somnolence, abnormal sensations other – elevated blood pressure, nasopharyngitis, elevated KL-6 fever, hair loss, abnormal taste, upper respiratory tract inflammation, puffiness herpes zoster, lethargy, tinnitus, cough, dysmenorrhea, candidiasis, bronchitis, pharyngitis, dry skin, palpitations, oropharyngitis, back pain, myalgias, chills, Cystitis, fungal disease [Contraindicated
Pregnant women or women with the possibility of pregnancy. This product has been found to be teratogenic in animal studies (rats), resulting in increased early fetal mortality and fetal arterial vasoconstriction.
Patients with severe liver disease. Because elamod has the potential to cause adverse effects of hepatic dysfunction, it may lead to further deterioration of pre-existing liver disease.
Patients with peptic ulcers, or a prior history of peptic ulcers. Elamod may cause further deterioration of existing peptic ulcers because of the potential for adverse reactions that may cause peptic ulcers.
Patients with a past history of hypersensitivity to the ingredients contained in this product.
Precautions]
1. Use with caution (the drug should be used with caution in the following patients)
Lactating women; patients with liver disease or a past history of liver disease; patients with low body weight; patients with anemia, leukopenia, thrombocytopenia; patients with low bone marrow function; patients with renal disease.
2. Basic precautions
(1) Hepatotoxicity: Due to the high incidence of aminotransferase elevation found in clinical trials, liver function tests must be performed before taking this product. Most aminotransferases are mildly elevated [≤ 2 times
Upper Limit of Normal (ULN)] and usually resolve with continued treatment; significant elevations (>3 times ULN) occur infrequently and may resolve with dose reduction or discontinuation of the drug. Most patients with elevated aminotransferases occur within 3 months of drug administration, and blood ALT and AST should be checked periodically during the initial phase of drug administration, at intervals that depend on the patient’s condition.
Use with caution in patients with liver damage and definite positive serology for hepatitis B or C. ALT should be checked before and monthly after dosing, at intervals depending on the patient’s condition.
If ALT elevation occurs during dosing, the principles of dose adjustment or interruption of treatment: ①If ALT elevation is 2 to 3 times the upper limit of normal, Elamod may be continued under close monitoring with the dose reduced to 25 mg/day. (2) If ALT is elevated 2 to 3 times the upper limit of normal value, if ALT is maintained at 2 to 3 times the upper limit of normal value and above 3 times after dose reduction, the drug must be discontinued and liver protection therapy must be intensified and closely observed.
(2) Active gastrointestinal diseases: Use with caution in patients with active gastrointestinal diseases. Patients should be informed to inform the doctor and go to the hospital as soon as possible in case of black stool, anemia, abnormal stomach/abdominal pain, etc. Once the diagnosis of gastric ulcer or duodenal ulcer is confirmed, the drug should be stopped immediately and symptomatic treatment should be given.
(3) Blood and kidney function tests must be performed before taking this product. Clinical symptoms should be adequately observed during the course of medication and properly handled when abnormalities are detected. It should be noted that when blood disorders such as erythrocytopenia, leukopenia and thrombocytopenia occur, the use of this product should be discontinued or suspended as needed and handled appropriately.
(4) Because of the possibility of interstitial pneumonia, attention should be paid to symptoms such as fever, cough, and dyspnea during the administration of this product, and appropriate treatment should be taken when abnormalities occur.
(5) Since the incidence of adverse reactions in patients with low body weight (less than 40 kg) has been found to be higher in clinical trials of this product alone, when this product is administered to patients with low body weight, adequate observation of the patient’s status should be made and appropriate treatment should be taken when abnormalities are detected.
(6) Since the efficacy and safety of the combination with anti-rheumatic drugs other than methotrexate have not been clarified, special attention should be paid to clinical observation of the combination.
(7) Since there is no clinical data on the effectiveness and safety of immunization with live vaccines during treatment, immunization with live vaccines should not be used during drug administration.
For pregnant and lactating women
Based on the results of reproductive toxicity tests in rats, it is contraindicated in women during pregnancy, lactation, and women with childbearing potential during treatment.
Pediatric Use]
Adequate and well-controlled studies on the efficacy and safety of this product have not been conducted in children and adolescents, and there are no reliable references. This product should be avoided in children and adolescents.
Geriatric Use]
No systematic safety studies have been conducted in elderly patients. The physiological functions of the elderly are generally reduced, and the patient’s condition should be observed during the use of the drug, and if used with caution under the guidance of a physician.
The literature reports that in clinical pharmacological trials in Japan with healthy adult men, drug concentrations in plasma were consistently slightly higher in the elderly than in the non-elderly. Although there was no difference in the effectiveness and incidence of adverse reactions in clinical trials of this product alone, the incidence of adverse reactions was higher in the elderly than in the non-elderly in combination trials with methotrexate.
Drug Interactions]
In vitro tests have shown that Eramod does not inhibit CYP2D6, CYP1A2, CYP2C9, CYP2C19 and CYP3A4, indicating that it does not affect the drugs metabolized by these enzymes by inhibiting the above P450 isozymes.
Contraindications to co-administration Literature reports.
Cases have been reported in which the effects of warfarin were potentiated when this product was co-administered with warfarin, which in turn caused severe bleeding. When patients must be treated with warfarin, it should be administered in preference to warfarin.
Co-administration precautions have been reported in the literature.
Combination with NSAIDs: NSAIDs and this product should be discontinued in the presence of peptic ulcers.
Combination with cimetidine: It may lead to an increase in the plasma concentration of the drug and an increased incidence of adverse reactions. When the abnormality occurs, the dosage of this product should be reduced, discontinued and other measures should be taken to deal with it properly.
Combined with phenobarbital: It may lead to a decrease in the plasma concentration of the drug.
Drug overdose]
The safety of overdose patients is not clear, and it is prohibited to administer more than 50mg per day. If the dose is too large or toxic reaction occurs, it is recommended to give activated charcoal or hemodialysis to eliminate.
Clinical trials
Phase II and Phase III multi-center clinical trials (780 cases in total) were conducted by a collaborative group led by Renji Hospital of Shanghai Jiaotong University School of Medicine.
Phase II clinical trial: A multicenter, randomized, double-blind, placebo-controlled design was used to evaluate the efficacy and safety of this product and to compare the difference in the dose-effect relationship and safety between the placebo group, 25mg group and 50mg group in patients with active rheumatoid arthritis. Dosage: 25mg group: 25mg (1 tablet) daily in the morning after meal, 1 time a day for 24 weeks; 50mg group: 25mg (1 tablet) daily in the morning and 2 times a day after dinner for 24 weeks. Efficacy and safety evaluations were performed at 6, 12, 18 and 24 weeks. The effectiveness was based on the American College of Rheumatology improvement criteria (ACR20, ACR50, ACR70). 288 patients with active rheumatoid arthritis were observed, and 280 evaluable cases were observed: 95 in the placebo group, 92 in the 25 mg group, and 93 in the 50 mg group. The results are shown in Table 1.
Table 1 Comparison of efficacy-time evaluation in placebo group, 25 mg group and 50 mg group (full analysis set)
Time Efficacy Placebo group
(N = 95) 25mg group
(N = 92) 50mg group
(N = 93) P value N % N % N % N % 6 weeks ACR20 13 13.68 27 29.3532 34.41 0.0012 ACR50 1 1.05 5 5.43 8 8.60 0.0188 ACR70 0 0 1 1.09 2 2.15 0.1543 12 weeks ACR20 21 22.11 33 35.87 42 45.16 0.0008 ACR50 7 7.37 14 15.22 17 18.28 0.0314 ACR70 2 2.11 3 3.26 6 6.45 0.1387 18-week ACR20 27 28.42 35 38.04 55 59.14 ＜0.0001 ACR50 8 8.42 17 18.48 23 24.73 0.0029 ACR70 2 2.11 11 11 11.96 10 10.75 0.0315 24 weeks ACR20 23 24.21 36 39.13 57 61.29 ＜0.0001ACR50 7 7.37 22 23.91 29 31.18 ＜0.0001ACR70 1 1.05 13 14.13 13.98 0.0028 Notes. Response to ACR20 was defined as a 20% improvement in the number of painful and swollen joints (28) in the patient as well as improvement in at least 3 of the following 5 items: ①. Subject-assessed pain (Visual Analogue Scale/Score, or VAS) scores; (ii). VAS scores for overall disease status as assessed by the subject; ③. (iii) VAS scores of overall disease status as assessed by the investigator; (iv) Health Assessment Questionnaire (HAN). Health Assessment Questionnaire (HAQ); ⑤. Acute phase reactants (blood sedimentation or C-reactive protein). 50% and 70% improvement in ACR50 and ACR70 were defined using the same criteria, respectively. The percentage improvement of each index = [(post-treatment value – pre-treatment value)/pre-treatment value × 100%].
The results of the trial showed that elamod started to work at 6 weeks of treatment, with statistically significant differences in efficacy between the placebo, 25 mg and 50 mg groups. the 25 mg group was more effective than the placebo group, and the 50 mg group was more effective than the 25 mg group.
Phase III clinical trial: A multicenter, randomized, double-blind, double-model, positive-controlled trial design was used to evaluate the efficacy and safety of this product and to compare the differences in the quantitative efficacy relationship and safety of methotrexate group, test group 1 and test group 2. The subjects were all patients with active rheumatoid arthritis.
Dosage: Methotrexate group: 1 dose of 10 mg (4 tablets) once a week during weeks 1-4; 1 dose of 15 mg (6 tablets) once a week during weeks 5-24; 24 weeks in total. Test group 1: Weeks 1-4: 25mg (1 tablet) daily in the morning after meals, 1 time per day; Weeks 5-24: 25mg (1 tablet) daily after breakfast and dinner, 2 times per day; for a total of 24 weeks. Test group 2: Weeks 1-24: 25 mg (1 tablet) each day after breakfast and dinner, twice a day for 24 weeks. Efficacy and safety evaluations were performed at 4, 10, 17 and 24 weeks, and the effectiveness evaluation was based on the American College of Rheumatology improvement criteria (ACR20, ACR50, ACR70). 492 patients with active rheumatoid arthritis were observed, and 489 evaluable cases were found in the methotrexate group: 163 cases, trial group 1: 163 cases, and trial group 2: 163 cases. The results of the trial are shown in Table 2.
Table 2 Comparison of efficacy-time evaluation of methotrexate group, trial group 1, and trial group 2 (full analysis set)
Time efficacy methotrexate group
(N=163) Trial group 1
(N=163) Trial group 2
(N = 163) P value N % N % N % N % 4-week ACR20 37 22.70 36 22.09 43 26.38 0.8801 ACR50 10 6.13 3 1.84 11 6.75 0.0659 ACR70 1 0.61 1 0.61 2 1.23 1.0000 10-week ACR20 87 53.37 64 39.26 77 47.24 0.0072 ACR50 27 16.56 21 12.88 30 18.40 0.3460 ACR7011 6.75 8 4.91 14 8.59 0.4912 Week 17 ACR20 97 59.51 76 46.63 91 55.83 0.0161 ACR50 52 31.90 44 26.99 47 28.83 0.3032 ACR70 22 13.50 15 9.20 23 14.11 0.2110 Week 24 ACR20 101 61.96 83 50.92 104 63.80 0.0397 ACR50 70 42.94 53 32.52 62 38.04 0.0457 ACR7034 20.86 27 16.56 30 18.40 0.2779 The results of the trial showed that the ACR20 of elamodex tablets was non-inferior (non-inferiority threshold of 10%) to methotrexate tablets at the endpoint of week 24.
Table 3 shows the changes in individual indicators in phase II and III clinical trials.
Table 3 Change in each indicator of ACR response criteria*
Individual indicators Placebo-controlled study Methotrexate – controlled study Phase II clinical trial (24 weeks) Phase III clinical trial (24 weeks) 25mg group
n=93 50mg group
n=94 Placebo group
n=95 Trial group 1
n=163 Trial group 2
n=163 Methotrexate
n=165 Number of painful joints 14.0 6.02.0 5.0 7.0 7.0 Number of swollen joints 14.5 6.0 2.0 4.0 4.0 4.0 5.0 Overall patient rating 218.0 30.0 5.0 30.0 28.0 30.0 Overall physician rating 218.5 31.0 3.0 27.0 25.0 30.0 Ability to perform daily living (HAQ) 0.25 0.40 0.10 0.40 0.40 0.45 Pain level 15.0 30.0 5.0 26.0 25.0 30.0 Erythrocyte sedimentation rate 3.5 12.0 -4.0 6.0 8.0 8.0 C-reactive protein 2.09 1.81 0.00 1.04 0.86 1.97 The following indicators are not included in the ACR response index Morning stiffness (min) 60.0 60.0 30.0 60.0 60.0 60.0 IgA _ _ _ _ 0.42 0.54 0.23 IgG _ _ _ _ 0.76 1.30 0.55 IgM _ _ _ _ 0.31 0.32 0.24 *Last Observation Carried Forward (LOCF): positive values indicate improvement
1Based on 28 joint counts
2Visual analogy scale 0=best, 100=worst
Pharmacology and Toxicology
Pharmacological effects
Eramod inhibited foot swelling and alleviated the destruction of bone and cartilage tissues in rats with collagenous arthritis model. The mechanism of action of Eramod is not fully understood. In the literature, it has been reported that in vitro elamod inhibits the activity of nuclear factor-κB (NF-κB), which in turn inhibits the production of inflammatory cytokines (interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor alpha). Elamod can also interact directly with mouse and human B cells in vitro to inhibit the production of immunoglobulins. In addition, it has been reported that elamod inhibits purified cyclooxygenase-2 (COX-2) activity in vitro (IC50=7.7 μg/mL), but has no effect on cyclooxygenase-1 (COX-1) activity.
Toxicological studies
Genotoxicity: The results of bacterial revertant mutation test, Chinese hamster lung V79 cells, lung fibrogenic CHL cells and human lymphocyte chromosome aberration test, and mouse micronucleus test for elamod were all negative.
Reproductive toxicity: Female and male rats given orally before mating showed a decrease in mating rate at doses up to 60 mg/kg/day (equivalent to approximately 10 times the recommended human dose, based on body surface area). During the embryonic developmental stage, the viability of fetal litters was significantly reduced in female pregnant rats given orally with elamod at 60 mg/kg/day. In female rats given orally during the perinatal period, at doses equal to or greater than 30 mg/kg/day, the pups showed slow weight gain and delayed physiological and neurological development.
Carcinogenicity.
2-year carcinogenicity test in mice
B6C3F1 mice were given 70, 200 and 700 mg/kg for 2 years by adulteration. The results showed that at doses above 200 mg/kg, the animals showed reduced food intake, inhibited body weight gain and reduced survival rate. The incidence of malignant lymphoma was seen to increase with increasing dose at doses above 70 mg/kg. A higher rate of death from malignant lymphoma after 79 weeks of administration was observed in both the elamod-administered and control groups. The tissue type of malignant lymphoma that appeared in the elamod administration group was predominantly follicular center cell lymphoma as in the control group, and the pathogenesis was identical to that of spontaneous malignant lymphoma in B6C3F1 mice. The malignant lymphoma observed in the elamod administration group was a tumor caused by the murine leukemia virus that occurs mostly in high-grade B6C3F1 mice, and the incidence of which was enhanced by elamod.
Renal cell adenoma developed in 3/16 males of surviving animals in the 700 mg/kg dose group. Renal cell adenomas occurred only in males in the 700 mg/kg group where an increased incidence or exacerbation of renal injury and regenerative and hyperproliferative changes were seen, whereas in females in the 700 mg/kg group and in the group below 200 mg/kg, the changes were not observed, and are therefore thought to be due to changes triggered by repeated renal injury and regeneration over time.
2-year carcinogenicity test in rats.
Rats were given alamod for 2.5, 8, and 25 mg/kg for 2 years by adulteration, and the results showed that a very mild decrease in food intake and inhibition of body weight gain was seen in the above 8 mg/kg dose group. A higher incidence of chronic interstitial nephritis, papillary necrosis, renal tubular dilatation, hyperplasia of the renal tubular epithelium, mineral deposition, and focal hemorrhages were seen in the kidneys of the animals in the 25 mg/kg dose group, and these changes were thought to be caused by a decrease in PG production due to COX-2 inhibition by elamod. There were no tumors induced by the administration of elamod in this trial.
Pharmacokinetics]
24 healthy volunteers, 12 cases in each group. Single dose group: divided into two dose groups of low 25mg and high 50mg. Multiple administration dose group: administered at a low dose of 25mg/dose, once in 12h for 6 days. Post-feeding dosing: single administration of 50 mg/dose orally was selected for subjects in the high dose group.
The pharmacokinetic properties of elamod in vivo conformed to the one-compartment model, with elamod exposure proportional to dose over the therapeutic dose range (25 mg to 50 mg) and no gender differences in key pharmacokinetic parameters. The bioavailability of elamod was not affected by food.
After oral administration of therapeutic doses of elamod, peak blood concentrations were reached at 3.1 to 4.6 hours. Steady-state concentrations were reached within 3 days after multiple dosing twice daily. The mean steady-state concentration was Cav of 0.76 ± 0.19 (μg/ml), mean apparent volume of distribution 0.20 L-kg-1, and mean plasma clearance 0.0133 L-h-1-kg-1
. The elimination half-life of elamod was 10.5 hours, and some accumulation of the drug in plasma was observed. Urinary drug excretion tests showed that only 0.0685 ± 0.056 % of the fasting group and 0.0608 ± 0.033 % of the diet group were eliminated from the kidneys as a prototype drug when 50 mg was administered orally, respectively.
A pharmacokinetic trial of the drug in the elderly was conducted in Japan, and the results of pharmacokinetic assays for single and repeated doses showed that the Cmax and AUC were slightly higher in the elderly than in the non-elderly.
Pharmacokinetic tests have not been conducted in children and patients with hepatic and renal insufficiency.
Storage】Store under shade and seal.
Package】Packaged in pharmaceutical laminate film. 7 tablets/box; 14 tablets/box; 21 tablets/box; 28 tablets/box; 56 tablets/box.
【Validity】 24 months
【Executive Standard】 YBH02802011
Approval Number】State Drug Administration H20110084
【Manufacturer】
Company Name: Xiangsheng Pharmaceutical Co.
Address: No. 3 Jinlian Road, Jinpan Industrial Zone, Haikou City, Hainan Province, China
Postal Code: 570216
Telephone number: 0898-66814532
Customer service hotline: 800-8289800 (only available from landlines, free of charge.)
400-8877552 (Can be dialed from cell phones and landline phones, charged according to local calls.)
Fax number: 0898-66814239
Web
Address: www.simcere.com