Hengrui heavy weight product apatinib mesylate revision manual!

Yesterday (January 21), the State Food and Drug Administration issued the "notice on Amending the instructions of apatinib mesylate tablets" According to the announcement, all manufacturers of apatinib mesylate tablets shall, in accordance with the measures for the administration of drug registration and other relevant regulations, put forward supplementary applications for the revision of apatinib mesylate tablets' instructions, and report to the provincial drug regulatory authorities for filing before March 10, 2020 If the revised contents involve drug labels, they shall be revised together; the instructions and other contents of the labels shall be consistent with the original approved contents Replace all drug instructions and labels that have been delivered within 6 months after the supplementary application is filed The above-mentioned apatinib mesylate tablet manufacturers shall conduct in-depth research on the mechanism of new adverse reactions, take effective measures to do a good job in the publicity and training of the use and safety issues, and immediately notify the drug dealers and users in an appropriate way in case of any change in the content related to drug safety, so as to guide doctors and pharmacists in the rational use of drugs [adverse reactions] added content: adverse event reports such as severe proteinuria, nephrotic syndrome, renal dysfunction, acute renal injury were detected after marketing, which may be related to the use of this product, other combined drugs or basic diseases of patients [note] add: Proteinuria / renal function damage: serious proteinuria, nephrotic syndrome, renal function abnormality, acute renal injury and other adverse events have been reported after listing Patients with renal insufficiency should be carefully used and closely monitored, and patients with autoimmune diseases, diabetes, hypertension and other diseases, as well as patients with combined use of other drugs that may have a potential impact on renal function should be focused on It is recommended to check the urine routine and renal function regularly during the medication If the urine protein ≥ + + twice in a row, 24-hour urine protein determination is required If other contents of the specification are inconsistent with the above revision requirements, they shall be revised together Data show that apatinib mesylate is a small molecule tyrosine kinase inhibitor independently developed by Hengrui medicine It can selectively inhibit the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR-2), thus inhibiting tumor angiogenesis and tumor growth In December 2014, apatinib mesylate was approved for the treatment of advanced gastric cancer with second-line chemotherapy failure Data from minenet shows that from 2015 to 2018, the terminal sales of apatinib mesylate in China's public medical institutions increased year by year, exceeding 2 billion yuan in 2018 Up to now, the research and development cost of relevant projects has been about 281.46 million yuan It is understood that at present, there are solafeinib, sunitinib and other similar products of apatinib mesylate at home and abroad, which have been approved for marketing Solafeinib was developed by Bayer company and approved to be listed in the United States as early as 2005; sunitinib was developed by Pfizer company and approved to be listed in the United States as early as 2006 According to the statistical data of the National Cancer Center, in 2015, there were 679100 new gastric cancer patients in China, with a growth rate of 3%, and 498000 gastric cancer patients died Although targeted treatment and immunotherapy have achieved good results in some solid tumors, there are no drugs for major breakthroughs in gastric cancer Apatinib is one of the three target drugs approved for gastric cancer indications Like the drugs O and K for immunotherapy, apatinib has been approved for the treatment of advanced gastric cancer or adenocarcinoma at the junction of stomach and esophagus According to the analysis of the information disclosed in the Mino database and the company's annual report, apatinib's sales increased by 23.56% in 2018 on the basis of 37% reduction in medical insurance negotiations If there are 680000 new patients per year according to the indications of gastric cancer, 25% of HER2 + patients will be removed, and there are nearly 500000 If gastric cancer accounts for 50%, apatinib's target patients will be 250000 According to the 3-month clinical use of apatinib, the market space is about 9.2 billion per year With the comprehensive implementation of medical insurance reimbursement in all regions, and the follow-up clinical data of other indications off label use, apatinib will continue to maintain a high growth trend, and the sales volume is expected to exceed 3.5 billion in the next three years How much influence this modification of the manual will have on Hengrui's heavy-duty product is worth further discussion On the same day, the State Food and Drug Administration issued another notice on Amending the specification of drugs containing Pipemidic Acid (No 2, 2020) 1、 Add warning words: This product has the risk of serious allergic reaction, including anaphylactic shock and severe skin allergic reaction In case of rash, pruritus, chills, dyspnea, blood pressure drop and other symptoms, stop the drug immediately and take appropriate measures; severe skin reaction should include erythema multiforme, Stevens Johnson syndrome, etc Toxic epidermal necrolysis (Lyell syndrome) 2、 [adverse reactions] is revised as follows: Gastrointestinal damage: nausea, vomiting, belching, stomach discomfort, dyspepsia, stomach pain, abdominal pain, abdominal distention, constipation, diarrhea, dry mouth, stomatitis Skin and its accessories: rash, pruritus, urticaria, maculopapular rash, erythema, hydroherpes, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis Mental and nervous system: headache, dizziness, vertigo, hypoesthesia, anorexia, anorexia, drowsiness, insomnia, epileptic seizure, spasm Systemic damage: chills, fever, anaphylaxis, anaphylactic shock, facial edema, fatigue, chest pain, angioneurotic edema Respiratory system: dyspnea, laryngeal edema Cardiovascular system: palpitation, cyanosis, flushing, hypotension, Henoch Schonlein purpura Urinary system: hematuria, urinary frequency, bun, creatinine increase Hepatobiliary damage: abnormal liver function, increased ast (got), ALT (GPT), and Al-P Blood system: leucopenia, thrombocytopenia, granulocytopenia Bone and muscle system: arthralgia, tendinitis 3、 Add the following content under [taboo]: 1 It is forbidden for pregnant women and lactating women 2 Prohibited for children under 18 years old 4、 [medication for pregnant and lactating women] is revised as follows: Animal experiments show that this product can inhibit the development of cartilage in young animals, and it is forbidden for pregnant women This product can be used in breast milk It is forbidden for lactating women 5、 [children's medication] is revised as follows The safety of this product in infants and under-18-year-olds has not been established However, when it is used in several kinds of young animals, it can cause joint diseases, and it is forbidden for children under 18 years old 6、 [medication for the elderly] is revised as follows: Because this product is mainly discharged through the kidney, the elderly patients often have renal dysfunction, so it needs to be reduced Pipemidic Acid Tablets are quinolones It interferes with the synthesis of bacterial DNA by acting on bacterial DNA gyrase, leading to bacterial death Clinically, it is mainly used for urinary tract, intestinal tract and ear tract infections caused by sensitive gram-negative bacilli and gram-positive staphylococci, such as urethritis, cystitis, bacillary dysentery, enteritis, otitis media, etc The toxicity of the drug is relatively low, and the main adverse reactions are nausea, belching, upper abdominal discomfort, anorexia, loose stool or constipation and other gastrointestinal reactions Cypress blue has 413 records in search of "Pipemidic Acid" on the official website of the State Food and drug administration, involving many enterprises According to data from minenet, from 2015 to 2018, the terminal sales of Pipemidic Acid in China's public medical institutions were relatively flat, and even reached a negative growth in 2017, with sales of 54.93 million in 2018 In combination with the top 20 brand pattern of Pipemidic Acid, Shandong Xinhua Pharmaceutical Co., Ltd accounts for a large proportion, and the other manufacturers share nearly 6% of the market.