[Medication for pregnant and lactating women]
Pregnancy: It may be harmful to the fetus if pregnant women use this product for treatment. Intravenous injection of 0.2 mg/kg (0.6 mg/m 2) or 5 mg/kg (15 mg/m 2) pemetrexed in mice with 6- 15 days of pregnancy is toxic and teratogenic to the fetus. Mice given pemetrexed at a dose of 0.2 mg/kg (about 1/833 recommended dose) can cause fetal malformation (incomplete ossification of talus and skull) and cleft palate, with a dose of 5 mg/kg (about 1/33 recommended dose). Embryotoxicity is mainly manifested in the increase of embryo mortality and the delay of embryo development. There is no research on pregnant women taking this product, because patients are advised to use contraception. If this product is used during pregnancy or the patient is pregnant during the use of this product, the potential danger to the fetus should be informed.
Breastfeeding: Whether this product or its metabolites can be secreted from milk has not been determined. However, this product may be potentially harmful to breastfed babies, and mothers who receive this product should stop breastfeeding.
[medication for children]
The safety and effectiveness of children's medication have not yet been determined.
[Medication for elderly patients]
According to the dose adjustment method of all patients, no special scheme is needed (see the special population section in pharmacokinetics).
[Drug Interaction]
Cisplatin does not change the pharmacokinetics of pemetrexed, and pemetrexed has no effect on the pharmacokinetics of all platinum drugs.
Vitamin-Oral folic acid and intramuscular injection of vitamin B 12 will not change the pharmacokinetics of pemetrexed.
The in vitro prediction of cytochrome P450 enzyme on drug metabolism-liver microglobulin showed that pemetrexed did not lead to the decrease of drug clearance rate through CYP3A enzyme, CYP2D6 enzyme, CYP2C9 enzyme and CYP 1A2 enzyme. The effect of pemetrexed on cytochrome P450 isoenzymes was not observed. Because, according to the recommended administration schedule (every 2 1 day 1 time), this product has no obvious induction effect on any enzyme.
Aspirin-Low to moderate doses of aspirin (325 mg every 6 hours) will not affect the pharmacokinetics of pemetrexed. The effect of high-dose aspirin on the pharmacokinetics of pemetrexed is unclear.
Ibuprofen-In patients with normal renal function, the daily dose of ibuprofen is 400mg, four times a day, which can reduce the clearance rate of pemetrexed by 20% (AUC increases by 20%). The effect of higher doses of ibuprofen on the pharmacokinetics of pemetrexed is unclear.
This product is mainly excreted from the urinary tract in the form of crude drug through glomerular filtration and renal tubular excretion. At the same time, giving drugs harmful to the kidney will delay the clearance of this product, and giving other drugs that increase the burden on renal tubules (such as probenecid) may also delay the clearance of this product.
For patients with normal renal function (patients with creatinine clearance rate of 3.80 ml/min), this product can be used together with ibuprofen (400mg, 4 times a day), but for patients with mild to moderate renal insufficiency (patients with creatinine clearance rate of 45 to 79 ml/min), this product should be used together with ibuprofen. Non-steroidal anti-inflammatory drugs with short half-life should not be used in patients with mild to moderate renal insufficiency 2 days before treatment, 1 day after treatment and 2 days after treatment.
The potential interaction between NSAIDs with long half-life and this product is uncertain. However, the treatment of NSAIDs should also be interrupted 5 days before treatment, the day of administration and 2 days after administration. If non-steroidal anti-inflammatory drugs must be used, it is necessary to closely monitor the toxic reactions, especially bone marrow suppression, renal and gastrointestinal toxicity.
[Drug overdose]
Only a few cases of overdose were reported. The main adverse reactions reported were neutropenia, anemia, thrombocytopenia, mucositis and rash. Predictable complications of drug overdose mainly include bone marrow suppression, manifested as neutropenia, thrombocytopenia and anemia. In addition, infection, diarrhea and mucositis may occur, with or without fever. In case of overdose, appropriate medical measures should be taken immediately under the guidance of a doctor.
In clinical research, if there is 4 degree leukopenia or 4 degree neutropenia for more than 3 days, formyltetrahydrofolate can be used, and if there is bleeding or 3/4 degree mucositis related to 4 degree thrombocytopenia or 3 degree thrombocytopenia, formyltetrahydrofolate should be used immediately. The recommended dosage and method of formyltetrahydrofolate are: intravenous administration, 1 the first dose is 100 mg/m 2, and then it is 50 mg/m 2, once every 6 hours, 1 time for 8 days.
The effect of dialysis on relieving overdose of this product has not been determined.
[Specification]
500mg/bottle100mg/bottle
[storage]
This product should be stored at room temperature (15-30 C).
The solution of this product prepared by the above method does not contain antibacterial preservatives, so it should be used immediately from the perspective of microorganisms and cannot be partially discarded. If it is not used up at one time, the prepared product solution can be stored in the refrigerator (2-8℃) or at room temperature (15-30℃), and its physical and chemical properties remain stable within 24 hours.
This product is not sensitive to light.
[Packaging] Glass bottles, 1 bottle/box
[Validity] 24 months.
relevant information
(1) has relevant information and introduction of products;
1, February 5, 2004-FDA announced the approval of alimta combined with cisplatin in the treatment of a rare malignant pleural mesothelioma. Alimta has been previously designated by the FDA as a rare drug to treat this indication, and it is also the first drug approved by the FDA to treat this disease.
2.Alimta is a new multi-target folic acid antagonist, which can block many enzymes needed for the separation and growth of cancer cells in folic acid channels. When one or more enzymes are blocked, cancer cells cannot grow and reproduce. At present, there are three different enzymes that can't target folic acid antagonists, so the previously approved raltitrexed for the treatment of advanced rectal cancer only acts on dihydrofolate reductase, which affects the synthesis of thymine. Alimta can act on three target enzymes, affecting the synthesis of thymine and adenine, so the action time is longer than other folic acid antagonists.
3. An American medical expert thinks that the anticancer drug Alimta of Lilly Company is safer than taxotere of Aventis SA Company, so it should be approved by the government to treat a common lung cancer. The expert group of FDA unanimously recommended to FDA with the voting result of 13-0 that they should approve this injectable drug for patients with non-small cell lung cancer after chemotherapy. However, these experts also pointed out that Lilly's data did not prove that Alimta (which has been approved for the treatment of asbestos-related pleural mesothelioma) can help lung cancer patients live longer than taxotere, so they suggested that the FDA ask Lilly to conduct more research, and when the company collects these data, patients can still buy this drug. The FDA usually adopts the recommendations of this group.
4. After the US Food and Drug Administration (FDA) approved Alimta (pemetrexed sodium) combined with cisplatin to treat malignant pleural mesothelioma in February, 2004, in May, 5438+ 10, the FDA approved Alimta as a second-line treatment drug for locally advanced lung cancer or metastatic non-small cell lung cancer, and the voting result of the FDA expert group was 10.
The FDA's rapid approval of Alimta for lung cancer treatment is based on the results of a phase III clinical study of second-line lung cancer treatment, which is by far the largest study in the world-"Alimta second-line lung cancer treatment phase III clinical trial". This study was completed in clinical centers in 20 countries and regions including the United States, Canada, Australia and Japan from March 438, 2006 to February 2002. This study compared the curative effects of alim Tower and Taxotere. The results showed that alim Tower was comparable to Taxotere in reducing tumor, but the incidence of neutropenia (abnormal leukopenia), agranulocytosis requiring hospitalization and alopecia caused by alim Tower was significantly lower than that of Taxotere.
5. Pemetrexed alimta is a new multi-target folic acid antagonist, which can inhibit thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide nucleotidyl transferase (GARFT), thus blocking the enzymes needed for tumor DNA replication and cell division and inhibiting tumor growth. The second phase clinical trial shows that it has good curative effect on recurrent non-small cell lung cancer. Hanna et al. reported a multi-center, randomized controlled phase III clinical trial, in which 57/kloc-0 patients were randomly divided into two groups: 500 mg/m2 intravenous pemetrexed, B 1 2, folic acid and dexamethasone on 1 day, and 75mg/m2 intravenous taxotere on1day. In another 57 clinical trials, the RR of pemetrexed or taxotere was 9.65438 0% and 8.8% respectively, and the median survival time was 8.3 months and 7.9 months respectively. Although pemetrexed has some side effects, it is well tolerated in clinic, so it may replace taxotere as a second-line treatment for advanced non-small cell lung cancer.
6. alim Tower VL SD 500MG Pemetrexed Disodium Intravenous Injection 1EA 2995 USD. Some websites also introduce it as 800kg/bottle.
(2) Classification of antineoplastic drugs:
According to the National Catalogue of Drugs for Basic Medical Insurance and Work Injury Insurance in 2005, the anti-tumor drugs are classified as follows:
1, cytotoxic drugs
1. 1 drugs acting on the chemical structure of DNA;
The representative drugs are busulfan, cyclophosphamide, platinum, nimustine and pirarubicin.
1.2 drugs affecting nucleic acid synthesis
Representative drugs are: fluorouracil, methotrexate, gemcitabine, capecitabine, etc. Retitlacet and pemetrexed, which are undergoing clinical trials, belong to this category.
1.3 drugs acting on nucleic acid transcription
Representative drugs are actinomycin, Pingyangmycin and so on.
1.4 topoisomerase DNA replication inhibitor
Representative drugs are: melphalan, topotecan, etc. Newly marketed drugs include irinotecan (Aili) for the treatment of advanced colon cancer.
1.5 drugs acting on tubulin synthesis
Representative drugs are: hydroxycamptothecin, etoposide, vinorelbine, docetaxel, paclitaxel and so on.
1.6 Other cytotoxic drugs
Representative drugs are: L-asparaginase.
2. Hormones and anti-hormonal anti-tumor drugs
Representative drugs are tamoxifen, anastrozole, letrozole, toremifene, exemestane and so on.
3, other and auxiliary drugs
The representative drugs are indirubin, tretinoin, calcium folinate and tropisetron.
(III) Principles of clinical application of antineoplastic drugs
The clinical application of anti-tumor drugs is not mechanically used according to the instructions, but often according to the proliferation dynamics of tumor cells to judge the patient's situation, and refer to the action mechanism of anti-tumor drugs to design a reasonable tumor treatment plan. Therefore, new drugs for tumors are not necessarily only used for indications in the instructions, but sometimes used for other tumors according to their mechanism of action. For example, platinum antineoplastic drugs, which belong to cell cycle nonspecific drugs, were first marketed to treat testicular cancer, but later widely used in the treatment of various tumors. Another example is gemcitabine, an anti-metabolic tumor drug, which is not limited to its two indications of non-small cell lung cancer and adenocarcinoma. Pemetrexed has multiple targets, which determines its great potential in clinical anti-tumor application.
Adjuvant drugs have no anti-tumor activity, but they are used to reduce the toxic and side effects of anti-tumor drugs or have sensitization effect, so they must be used in combination with anti-tumor drugs for tumor treatment.
(4) Market information of antineoplastic drugs
1, China tumor spectrum
Ranked men and women
Name of tumor, number of deaths, number of new cases, name of tumor, number of deaths, number of new cases
1 lung cancer 124,1221,128 lung cancer 6 1, 379 64,351
2 gastric cancer 52380 85636 breast cancer 18095 60626
Liver cancer 69,967 64,381gastric cancer 25,856 39,205
4 Rectal cancer 25 563 39 244 Rectal cancer 265 438+0 443 36 500
5 Esophageal cancer 27,220 32,332 Liver cancer 26,233 22,840
Leukemia 8923 9 166 Leukemia 6874 6753
Note: Non-small cell lung cancer accounts for more than 80% of the total lung cancer.
1, a commonly used anti-tumor drug for the treatment of non-small cell lung cancer.
Manufacturer's name, dosage form, specifications, retail price and average daily treatment fee.
Docetaxel powder injection 20mg/ tablet 1993 yuan/tablet of Aventis about 664 yuan/day.
Changchun Ruibin Injection 10mg/ 1ml 340.2/ 260 yuan of Lianyungang Haosen Pharmaceutical Co., Ltd. per day.
Paclitaxel injection 30mg/5ml 980 yuan/branch Sichuan Taiji Pharmaceutical Co., Ltd. is about 373 yuan/day.
Gemcitabine powder injection 1g/ bottle 2464/ bottle of French Lilly is about 704 yuan/day.
Gemcitabine powder injection 1g/ bottle 1606/ bottle Jiangsu Haosen Pharmaceutical Co., Ltd. 460 yuan/day or so.
Cisplatin lyophilized powder for injection 10mg/ 26 yuan/Qilu Pharmaceutical Factory about 20 yuan/day.
Carboplatin injection150mg/15ml158.8/30 yuan Branch of Shanghai Hualian Pharmaceutical Co., Ltd. for about one day.