Capecitabine, the first anti-tumor drug imitated by Hengrui medicine, will be approved for market this month

Hengrui medicine capecitabine tablet is about to be approved, making its first imitation in China According to the information on CFDA's website, the drug review status is "under approval" and waiting for CFDA's signature People from the Securities Affairs Department of the company disclosed to the media that the company has made preparations for the production and listing of the products, and the products can be listed for sale after being approved "It will be available this month." At the end of last year, the company has obtained the approval for the production of capecitabine API According to the public information, capecitabine is the first oral fluoropyrimidine carbamate anti-tumor drug, which is a new targeted drug for the treatment of breast cancer and colorectal cancer The original manufacturer of the drug is Roche pharmaceutical company of Switzerland In 2007, capecitabine's global sales reached US $1.02 billion, and in 2008, US $1.142 billion At present, the domestic market of capecitabine is mainly dominated by Roche and its joint venture Shanghai Roche company Capecitabine occupies 3.59% of the market share of the whole anti-tumor drug hospital market in China in 2011, ranking first in all anti metabolism tumor drugs According to the information on CFDA website, there are no domestic enterprises producing capecitabine preparation, and there are nearly 20 enterprises applying for the production of capecitabine except Hengrui medicine It is worth mentioning that capecitabine's patent in China will expire on December 17 Industry insiders pointed out that Evergrande pharmaceutical capecitabine will become the first domestic imitation after being listed, and it is expected to quickly seize the market share of the original research drug P yrimidin-2 (1H) - one; 5 '- deoxy-5-fluoro cytidine Chemical name: 5 '- deoxy-5-fluoro-n - [(pentoxy) carbonyl] cytidine Chinese alias: 5-deoxy-5-fluoro-n - [(pentoxy) carbonyl] - cytosine nucleoside; 5-deoxy-5-fluoro-n - [(pentoxy) carbonyl] - cytosine nucleoside; capecitabine; capecitabine trade name: Xeloda formula: c15h22o6n3f CAS No: 154361-50-9; 158798-73-3 molecular weight: 359.35 weight loss on drying: ≤ 1.0% content: more than 99.0% related substances: < 0.5% melting point 110-121 ℃ indications: Xeloda is suitable for the further treatment of paclitaxel and advanced primary or metastatic breast cancer including anthracycline antibiotic chemotherapy program which is ineffective; single drug first-line treatment of metastatic rectal cancer Contraindications: serious side effects of Xeloda or allergic history of fluorouracil (metabolite of capecitabine) are prohibited Adverse reactions and precautions common adverse reactions include nausea, vomiting, oral ulcer, abdominal pain, diarrhea, loss of appetite, skin changes It is also reported that some patients have transient myelosuppression, hair loss, increased tear, headache, dizziness Capecitabine is a kind of bone marrow inhibitor, so it is necessary to check the blood before each use to monitor the blood cell and platelet count This product has toxic and side effects of liver, so it is necessary to check the liver function regularly In addition, cardiac function should also be monitored to avoid irreversible toxic reactions If intravenous infusion is needed, the function of the above organs should be analyzed before medication Capecitabine may cause damage to the fetus, so it can not be used in pregnant women; women who use the drug should not be pregnant Even after the treatment, the drug may have an impact on fertility In the clinical trial of capecitabine, no side effects caused by drug overdose were found However, in animal experiments (for monkeys, 25679mg / m2 / day) and for humans, the drug overdose was manifested as nausea, vomiting, diarrhea, gastrointestinal irritation, gastrointestinal bleeding and myelosuppression Treatment should include the use of diuretic dehydration treatment, dialysis treatment if necessary Although there is no clinical report on the treatment of Xeloda overdose with dialysis, dialysis may be beneficial to reduce the concentration of 5 '- DFUR in the circulation, which is a low molecular weight metabolite of capecitabine Symptoms: nausea and vomiting, diarrhea, gastrointestinal irritation and bleeding, myelosuppression Treatment: drug intervention support treatment, discontinuation of medication, dose adjustment 2 The usage and dosage of the medicine are 2500mg / m2 daily for two weeks and rest for one week The total daily dose was swallowed twice in the morning and half an hour after the meal If the disease continues to deteriorate or produces intolerable toxicity, the treatment should be stopped Tables metastatic burst cancer 2500 mg / m2 / day in two divided doses about 12 hr apart at the end of a mean for 2 weeks Follow by a 1-week rest period (i.e., 3-week cycles) Once the dose is reduced, it cannot be increased later The following is the recommended dose for dose adjustment of toxicity (according to the common toxicity standard established by the National Cancer Institute of Canada) Level 1 and level 2: first occurrence: stop the treatment until it recovers to level 0-1, and carry out the next treatment course according to 100% of the maintenance dose The second occurrence: stop the treatment until it returns to level 0-1, and carry out the next treatment course according to 75% of the maintenance dose The third occurrence: stop the treatment until it returns to level 0-1, and carry out the next treatment course according to 50% of the maintenance dose Fourth occurrence: permanent cessation of treatment Level 3: first occurrence: stop the treatment until it recovers to level 0-1, and carry out the next treatment course according to 75% of the maintenance dose The second occurrence: stop the treatment until it returns to level 0-1, and carry out the next treatment course according to 50% of the maintenance dose Third occurrence: permanent cessation of treatment Level 4: permanent cessation of treatment If the treatment needs to be continued after discontinuation, the maximum benefit of the patient should be considered, and 50% of the recommended dose should be used when the toxic symptoms return to level 0-1 Foreign multicenter clinical studies (j.l.blum et al., j.clin Oncol 17:4851999) · 162 patients with advanced breast cancer, failed chemotherapy (including paclitaxel) in the past, took Xeloda 2510mg / m2 / day for 2 weeks, rested for 1 week, repeated every 3 weeks, a total of 6 cycles Results: Cr3 cases, pr24 cases, total effective rate of 20%, median remission time of 241 days, median ttp93 days, Mst384 days · major adverse reactions (grade III-IV): hand foot syndrome 9.9%, diarrhea 14.2%, mucositis 4.3% The main purpose of this study is to evaluate the total effective rate of Xeloda in the second-line chemotherapy for Chinese patients with advanced breast cancer The selected breast cancer patients were treated with Xeloda single drug, 2510mg / m2 daily, twice a day, orally, and delivered with warm boiled water It is a course of treatment to stop taking medicine for 7 days for 14 days in a row Patients are required to take medicine for at least 2 courses, while patients with Cr, PR and SD are required to take medicine for 4 courses This study includes outpatient patients who are able to take care of themselves They must be informed that they should stop taking medicine temporarily and contact the doctor in time to decide further treatment in case of adverse reactions According to WHO standard, this study is an open, multicenter, non control trial The selected breast cancer patients were treated with Xeloda single drug, 2510mg / m2 daily, twice a day, orally, and delivered with warm boiled water It is a course of treatment to stop taking medicine for 7 days for 14 days in a row Patients are required to take medicine for at least 2 courses, while patients with Cr, PR and SD are required to take medicine for 4 courses This study includes outpatient patients who are able to take care of themselves They must be informed that they should stop taking medicine temporarily and contact the doctor in time to decide further treatment in case of adverse reactions Trial use of Xeloda: 2510mg / m2 / day, two times in the morning and evening, 14 days in a row, 7 days out of medication for one cycle, at least two cycles of medication for 71 patients with China's advanced second-line breast cancer, 67 cases can be evaluated Results according to ITT evaluation, the total effective rate confirmed by the reexamination after 4 weeks is 32.39% The therapeutic effect is similar to or slightly higher than that reported in foreign clinical trials It is proved that this product can be used as an effective drug in the treatment of advanced breast cancer after the failure of routine treatment such as adriamycin and paclitaxel 2 The main adverse reactions of this product are hand foot syndrome, nausea and vomiting, leucopenia, etc Diarrhea can also occur in some patients The adverse reactions of most patients were mild I-II, but a few patients also had serious adverse reactions This product should be used under close observation by a specialist experienced in tumor chemotherapy 3 It is suggested that the product can be approved for use in China Liver dysfunction in special population: the pharmacokinetic study of Xeloda in patients with mild to moderate liver dysfunction caused by liver metastasis shows that dose adjustment is not necessary for such patients Renal insufficiency: the pharmacokinetics of Xeloda has not been studied in patients with renal insufficiency Children: the efficacy and safety of Xeloda has not been studied in children Elderly: dose adjustment is not necessary However, capecitabine is more toxic in the elderly (over 65 years old) than in the young, so it should be monitored closely Pregnant and lactating women: the clinical study of Xeloda has not been carried out in pregnant women, but it must be considered that if Xeloda is used in such patients, it may cause fetal damage Animal experiments show that capecitabine can cause fetal death or deformity These findings suggest that capecitabine derivatives also have this effect and therefore cannot be used in pregnant women When using Xeloda during pregnancy or when pregnancy occurs during the use of Xeloda, the potential risk of fetal injury or teratogenesis must be considered Birth control measures must be taken when using Xeloda Although it is not known whether Xeloda can be secreted in the milk, because many drugs can be secreted in the milk, there is a potential risk of serious side effects on breastfeeding babies, so it is recommended that women who use Xeloda stop breastfeeding Prevention measures should limit the dose of toxicity including diarrhea, abdominal pain, nausea, gastritis and hand foot syndrome Nearly half of the patients receiving Xeloda treatment will induce diarrhea, and those with severe diarrhea due to dehydration should be closely monitored and given rehydration treatment Diarrhea 4-6 times a day or diarrhea at night is level 2, diarrhea 7-9 times a day or fecal incontinence and absorption disorder is level 3, diarrhea more than 10 times a day or bloody stool with naked eyes and need intravenous rehydration is level 4 In case of grade 2, 3 or 4 diarrhea, Xeloda should be stopped until the diarrhea stops or the number of diarrhea is reduced to grade 1 Use of Xeloda should be reduced after grade 3 or 4 diarrhea Nearly half of the patients who used Xeloda developed HFS, but most of them were grade 1-2, while grade 3 was rare Most of the side effects can be eliminated Although it is necessary to stop the medication temporarily or reduce the dosage, it is not necessary to stop the treatment for a long time The side effects of Xeloda are less The following may be related to it: digestive system: the most common side effects of Xeloda are reversible gastrointestinal reactions, such as diarrhea, nausea, vomiting, abdominal pain, gastritis, etc Serious (3-4 grade) side effects are relatively rare Skin: HFS in almost half of patients using Xeloda: numbness, insensitive