How to calculate the dose of Lipitor

This proct should be used under the guidance of a qualified doctor who has experience in the application of anti-tumor chemotherapy. This proct can only be used for intravenous drip, and its solution must be prepared according to the instructions of [u] preparation for intravenous drip[ u] Malignant pleural mesothelioma: [/ u] the recommended dose of this proct combined with cisplatin for the treatment of malignant pleural mesothelioma is 500 mg / m2 every 21 days for more than 10 minutes, and the recommended dose of cisplatin is 75 mg / m2 for more than 2 hours. Cisplatin should be given 30 minutes after the end of administration. Cisplatin treatment requires hydration. Please refer to cisplatin instructions for details[ u] Predrug: [/ u] corticosteroids - patients who did not predrug corticosteroids had a higher incidence of rash. Pretreatment with dexamethasone (or similar drugs) can rece the incidence and severity of skin reactions. Method of administration: Dexamethasone 4mg orally, twice a day, one day before administration, one day after administration and one day after administration for three days. Vitamin supplement - in order to rece toxicity, low dose folic acid or other multivitamin preparations containing folic acid must be taken at the same time. Taking time: take at least 5 doses of folic acid in the next day 7 days before the first treatment, and take it all the time for the whole treatment cycle, and stop taking it 21 days after the last treatment. Patients should also be given intramuscular injection of vitamin B12 within 7 days before the first administration, and then intramuscular injection every 3 cycles. The later administration of vitamin B12 can be carried out on the same day as this drug. The dosage of folic acid was 350-1000 μ g. The usual dose is 400 μ g: Vitamin B12 dose 1000 μ g( See the "warning" section under [precautions])[ u] Laboratory examination monitoring and recommended dose adjustment method: [/ u] monitoring - all patients who are ready to receive this drug should complete blood cell examination including platelet count before medication, monitor the lowest point and recovery of blood cells after medication, and check the above items at the beginning of each cycle, the 8th day and the 15th day of clinical study. Only when neutrophils ≥ 1500 / mm [sup] 3 [/ sup], platelets ≥ 100000 / mm [sup] 3 [/ sup], and creatinine clearance rate ≥ 45ml / min, can patients start the treatment. Biochemical examination of liver function and renal function should be carried out every cycle of treatment. Recommended dose adjustment method - dose adjustment based on the lowest blood cell count and the most severe non hematological toxicity in previous cycles. If the 21 day cycle does not recover from adverse reactions, the treatment should be delayed. After waiting for the patients to recover, they were treated according to the requirements of Table 1, table 2 and table 3. Table 1: hematologic toxicity caused by this proct (single drug or combined drug) and cisplatin dose adjusted neutrophil minimum value < 500 / mm3 and platelet minimum value ≥ 50000 / mm3 75% of the original dose (two drugs) platelet minimum value ≤ 50000 / mm3 no matter what the neutrophil minimum value is, 50% of the original dose (two drugs) if the patient has non hematologic toxicity of ≥ 3 degrees (excluding neurotoxicity) The treatment should be stopped until it returns to the pre-treatment level or slightly lower than the pre-treatment level. Start the treatment again and treat according to the requirements of Table 2. Table 2: dose adjustment of this proct (single drug or combined drug) and cisplatin e to non hematological toxicity a, B dose of this proct (mg / m2) cisplatin dose (mg / m2) 75% of the original dose of any degree 3 C or 4 non hematological toxicity other than mucositis 75% of the original dose of diarrhea requiring hospitalization (regardless of grade) or degree 3 75% of the original dose of 4-degree diarrhea, 75% of the original dose of 3-degree or 50% of the original dose of 4-degree mucositis, 100% A. NCI's CTC standard B does not include neurotoxicity, C does not include neurotoxicity caused by elevation of 3-degree transaminase. The dose adjustment of this proct and cisplatin is shown in Table 3. If grade 3 or 4 neurotoxicity occurs, treatment should be stopped. Table 3: dose adjustment of this proct (single drug or combined drug) and cisplatin caused by neurotoxicity CTC grading: dose of this proct (mg / m2) dose of cisplatin (mg / m2) 0-1 100% of the original dose 100% of the original dose 2 50% of the original dose 100% of the original dose, In case of grade 3 / 4 hematological or non hematological toxicity (excluding grade 3 transaminase elevation), the treatment should be stopped. In case of grade 3 or 4 neurotoxicity, the treatment should be stopped immediately. Patients with renal insufficiency - as long as the creatinine clearance rate of patients is greater than or equal to 45ml / min, the dose adjustment method of all patients is followed, and there is no special dose adjustment method. The dose adjustment method for creatinine clearance rate lower than 45ml / min has not been determined. Therefore, when the creatinine clearance rate [45ml / min] calculated by Cockcroft Gault formula or Tc99m dpta serum clearance method is used to calculate glomerular filtration rate, the drug should not be given. Male: [u] (140 age) × Actual body weight (kg) [/ u] = ml / min 72 × Serum creatinine (mg / dl) female: male creatinine clearance rate × 85 creatinine clearance rate [80 ml / min], if this proct is combined with non steroidal anti-inflammatory drugs, it should be vigilant and closely monitored See [drug interactions]) patients with liver dysfunction - this proct is not metabolized by the liver. The dose adjustment of liver dysfunction is shown in Table 2 See "patients with liver dysfunction" under [precautions])[ u] Precautions for dispensing and administration: [/ u] this proct is an anti-tumor drug. Like other potentially toxic anti-tumor drugs, special care should be taken when handling and dispensing this proct. Gloves are recommended. If the injection comes into contact with the skin, wash thoroughly with soap and water immediately. If the injection comes into contact with the mucous membrane, wash thoroughly with water. At present, there is no uniform recommendation standard for the disposal of anticancer drugs. This proct is not erosive agent, no specific antidote. So far, there are several cases of extravasation of this injection, but the researchers think it is not serious. The extravasation treatment of this proct can be carried out according to the conventional method of non erosive agent treatment[ u] Preparation for intravenous infusion: [/ u] 1. 2. Calculate the dosage and number of the drug. Each drug contained 500mg pemetrexed. The actual content of pemetrexed in each bottle is more than 500mg to ensure that the marked amount can be reached ring intravenous drip. 3. Each 500mg drug is dissolved into 25mg / ml solution with 20ml 0.9% sodium chloride injection (without preservative), and slowly rotated until the powder is not completely dissolved. It is normal for the completely dissolved solution to be clear and colorless to yellow or yellow green. The pH value of the solution is 6.6-7.8. And the solution needs further dilution. 4. Observe whether there is precipitation and color change before intravenous drip; If there is any abnormality, do not drip. 5. After the preparation of the drops, the solution should be diluted to 100ml with 0.9% sodium chloride injection (without preservative) and intravenous drip for more than 10 minutes. 6. The prepared solution should be refrigerated in refrigerator or placed at room temperature (15-30 ℃) without avoiding light. Its physical and chemical properties should be stable within 24 hours. The solution prepared according to the above method does not contain antibacterial preservatives. No partial discarding. This proct is only recommended to be dissolved and diluted with 0.9% sodium chloride injection (without preservative). This proct is insoluble in diluents containing calcium, including USP Ringer's lactate injection and USP Ringer's injection. Whether other diluents and other drugs can be mixed with this proct has not been determined, so it is not recommended

[indications]
this proct combined with cisplatin is used for the treatment of inoperable malignant pleural mesothelioma
[usage and dosage]
this proct should be used under the guidance of a qualified doctor with anti-tumor chemotherapy experience. This proct can only be used for intravenous drip, and its solution must be prepared according to the instructions for intravenous drip preparation
malignant pleural mesothelioma:
the recommended dose of this proct combined with cisplatin for the treatment of malignant pleural mesothelioma is 500 mg / m2 every 21 days for more than 10 minutes, and the recommended dose of cisplatin is 75 mg / m2 for more than 2 hours. Cisplatin should be given 30 minutes after the end of administration. Cisplatin treatment requires hydration. Please refer to cisplatin instructions for details
predrug:
corticosteroids - patients without predrug of corticosteroids have a higher incidence of skin rash
pretreatment with dexamethasone (or similar drugs) can rece the incidence and severity of skin reactions. Methods of administration: Dexamethasone 4mg was taken orally twice a day,
one day before administration, on the day of administration and one day after administration for three consecutive days< In order to rece the toxicity, low dose folic acid or other compound vitamin preparations containing folic acid must be taken at the same time. Taking
time: take at least 5 doses of folic acid for the next day 7 days before the first administration of this proct, and take it all the time for the whole treatment cycle, and stop taking it 21 days after the last administration of this proct. Patients should also be given intramuscular injection of vitamin B12 within 7 days before the first administration, and then intramuscular injection every 3 cycles. The later administration of vitamin B12 can be carried out on the same day as this drug. Dosage of folic acid: 350-1000 μ g. The usual dose is 400 μ g: Vitamin B12 dose 1000 μ g( See the warning section under [precautions]<
recommended dose adjustment method for laboratory examination monitoring:
monitoring - all patients who are ready to receive the treatment of this proct should complete blood cell examination including platelet count before medication, and monitor the lowest point and recovery of blood cells after administration. The above items should be checked at the beginning of each cycle, the 8th day and the 15th day of clinical study. Patients must be neutrophils ≥ 1500 / mm3, platelets ≥ 1000000 cells / mm3, creatinine clearance rate ≥ 45ml / min before starting the treatment. Biochemical examination of liver function and renal function should be carried out every cycle of treatment
the first dose adjustment method is recommended to adjust the dose according to the lowest blood cell count and the most serious non hematological toxicity in the previous cycle. If the 21 day cycle does not recover from adverse reactions, the treatment should be delayed. After waiting for the patients to recover, they were treated according to the requirements of Table 1, table 2 and table 3
Table 1: dose adjustment of this proct (single drug or combined drug) and cisplatin e to hematological toxicity
neutrophil minimum & lt; No matter what the minimum value of neutrophils is, 50% of the original dose
if the patient has non hematologic toxicity (excluding neurotoxicity) of degree 3 or more (excluding elevation of degree 3 transaminase), the treatment should be stopped, Until it returns to the pre-treatment level or slightly lower than the pre-treatment level. Start the treatment again and treat according to the requirements of Table 2
Table 2: dose adjustment of this proct (single drug or combined drug) and cisplatin e to non hematological toxicity a, B
dose of this proct (mg / m2) cisplatin dose (mg / m2)
75% of the original dose of 75% of the original dose of any degree 3 C or 4 non hematological toxicity except mucositis
diarrhea requiring hospitalization (regardless of grade) or degree 3 75% of the original dose of grade 4 diarrhea, 75% of the original dose of grade 3 mucositis or 50% of the original dose of grade 4 mucositis, 100% of the original dose of grade 4 mucositis. The CTC standard of NCI
B does not include neurotoxicity
C does not include neurotoxicity caused by elevation of grade 3 transaminase. The dose adjustment of this proct and cisplatin is shown in Table 3. If grade 3 or 4 neurotoxicity occurs, treatment should be stopped
Table 3: dose adjustment of this proct (single drug or combined drug) and cisplatin e to neurotoxicity
CTC graded dose of this proct (mg / m2) cisplatin dose (mg / m2)
100% of the original dose of 0-1
50% of the original dose of 2
if the patient experiences two dose adjustments, In case of grade 3 / 4 hematological or non hematological toxicity (excluding grade 3 transaminase elevation), the treatment should be stopped. In case of grade 3 or 4 neurotoxicity, the treatment should be stopped immediately
elderly patients -- patients over 65 years old do not need special adjustment except for the above dose adjustment scheme
children - this proct is not recommended for children, and its safety and efficacy have not been determined
patients with renal insufficiency - as long as the creatinine clearance rate of patients is greater than or equal to 45ml / min, the dose adjustment method of all patients is followed, and there is no special dose adjustment method. The dose adjustment method for creatinine clearance rate lower than 45ml / min has not been determined. Therefore, when the glomerular filtration rate was calculated according to Cockcroft Gault formula or Tc99m dpta serum clearance method, the creatinine clearance rate & lt; 45 ml / min, this proct should not be given treatment
[140 age] × Actual body weight (kg)
male: --- --- --- = ml / min
72 × Serum creatinine (mg / dl)
female: male: creatinine clearance rate × 85
creatinine clearance rate & lt; Patients with 80 ml / min should be vigilant and closely monitored if the drug is combined with non steroidal anti-inflammatory drugs Refer to [drug interaction])
patients with liver dysfunction - this proct is not metabolized by liver. The dose adjustment of liver dysfunction is shown in Table 2 Please refer to the part of patients with liver dysfunction under [precautions]
precautions for dispensing and administration:
this proct is an anti-tumor drug. Like other potentially toxic anti-tumor drugs, special care should be taken when handling and dispensing this proct. Gloves are recommended. If the injection comes into contact with the skin, wash thoroughly with soap and water immediately. If the injection comes into contact with the mucous membrane, wash thoroughly with water. At present, there is no uniform recommendation standard for the disposal of anticancer drugs
this proct is not an erosive agent and has no specific antidote. So far, there are several cases of extravasation of this injection, but the researchers think it is not serious. The extravasation treatment of this proct can be carried out according to the conventional method of non erosive agent treatment
preparation for intravenous drip:
1. Aseptic operation should be performed in the configuration process
2. Calculate the dosage and the number of drug. Each drug contains 500 mg of this proct. The actual content of this proct in each bottle is more than 500mg to ensure that the marked amount can be reached ring intravenous drip
3. Dissolve each 500mg drug into 25mg / ml solution with 20ml 0.9% sodium chloride injection (without preservative), and slowly rotate until the powder is not completely dissolved. It is normal for the completely dissolved solution to be clear and colorless to yellow or yellow green. The pH value of the solution is 6.6-7.8. And the solution needs further dilution
4. Before intravenous drip, observe whether there is precipitation and color change in the solution: if there is any abnormality, do not drip
5. Diluted to 100ml with 0.9% sodium chloride injection (without preservative) after the preparation, intravenous drip for more than 10 minutes
6. The prepared solution should be refrigerated in refrigerator or placed at room temperature (15-30 ℃) without avoiding light, and its physical and chemical properties should be stable within 24 hours. The solution prepared according to the above method does not contain antibacterial preservatives. No partial discarding. This proct is only recommended to be dissolved and diluted with 0.9% sodium chloride injection (without preservative). This proct is insoluble in diluents containing calcium, including USP Ringer's lactate injection and USP Ringer's injection. Whether other diluents and other drugs can be mixed with this proct has not been determined, so it is not recommended

Only a few cases of overdose were reported. The main adverse reactions reported were neutropenia, anemia, thrombocytopenia, mucositis and rash. The major complications of drug overdose were myelosuppression, including neutropenia, thrombocytopenia and anemia. In addition, infection, diarrhea and mucositis with or without fever may occur. In case of drug overdose, appropriate medical measures should be taken immediately under the guidance of doctors. In clinical studies, formyltetrahydrofolate can be used if there is grade 4 leukopenia or grade 4 neutropenia for more than 3 days. If there is grade 4 thrombocytopenia or grade 3 thrombocytopenia related bleeding or grade 3 / 4 mucositis, formyltetrahydrofolate should be used immediately. The recommended dosage and method of formyltetrahydrofolate is: intravenous administration, the first dose is 100mg / m2, then 50mg / m2, once every 6 hours for 8 days. The role of dialysis in relieving the overdose has not been determined

Warning: for patients with reced renal function, this proct is mainly excreted in the form of technical drug through urinary tract. If the creatinine clearance rate is more than or equal to 45ml / min, no dose adjustment is needed. For patients with creatinine clearance rate [45ml / min], there is not enough research data of patients to give the recommended dose. Therefore, patients with creatinine clearance rate [45ml / min] should not be treated with this proct See "recommended dose adjustment method" in [usage and dosage]. In the clinical study, a patient with severe renal insufficiency (creatinine clearance rate 19 ml / min) who did not receive folic acid and vitamin B12 supplement treatment died of drug-related toxicity after receiving single drug treatment. Myelosuppression this proct can cause myelosuppression, including neutropenia, thrombocytopenia and anemia (see [adverse reactions]). Myelosuppression is a common dose limiting toxicity. The dose should be adjusted according to the lowest neutrophil and platelet values and the most serious non hematological toxicity in the previous treatment cycle See "recommended dose adjustment method" in [usage and dosage]. Folic acid and vitamin B12 should be supplemented with folic acid and vitamin B12 to prevent or rece hematological or gastrointestinal adverse reactions Please refer to the usage and dosage section. Clinical studies have shown that patients receiving folic acid and vitamin B12 supplementation have a lower incidence of total adverse reactions, including 3 / 4 degree hematologic toxicity and non hematologic toxicity, such as neutropenia, neutropenic fever and 3 / 4 degree granulocytopenic infection. Precautions general precautions this proct should be used under the guidance of a qualified doctor with anti-tumor drug application experience. It should be treated in medical institutions with sufficient diagnosis and treatment technology, which can also ensure the timely treatment of complications. The treatment-related adverse reactions seen in clinical studies can be recovered. Patients who were not pretreated with corticosteroid before administration were prone to skin rash. Pretreatment with dexamethasone (or similar drugs) can rece the incidence and severity of skin reactions It is unclear whether this proct causes retention of body fluids, such as pleural effusion or ascites. For patients with body fluid retention with obvious clinical symptoms, drainage of body cavity effusion before medication can be considered. Laboratory examination of all patients who are ready to accept the treatment of this proct, the medication said that blood cell examination including platelet count and blood biochemical examination should be completed, the lowest point and recovery of blood cells should be monitored after administration, and the above items should be checked at the beginning of each cycle, the 8th day and the 15th day of clinical study. Patients need neutrophils ≥ 1500 / mm [sup] 3 [/ sup], platelets ≥ 1000000 cells / mm [sup] 3 [/ sup], and creatinine clearance rate ≥ 45ml / min before starting the treatment. Patients with liver dysfunction [bilirubin] 1.5 times of the normal upper limit were not included in the clinical study; patients without liver metastasis [transaminase] 3.0 times of the normal upper limit were not included in the clinical study; Patients with liver metastasis, if the transaminase is between 3.0 and 5.0 times the upper limit of normal, will be included in the clinical study. The dose adjustment of patients with liver dysfunction is shown in Table 2 Refer to the "special population" section of [pharmacokinetics]. In patients with renal insufficiency, this proct is mainly excreted through the kidney. Compared with patients with normal renal function, the overall clearance rate of patients with renal insufficiency decreased and AUC increased. In patients with moderate renal insufficiency, the safety of cisplatin combined with this proct has not been determined (see "special population" section under [pharmacokinetics]). The interaction between the drug and laboratory tests has not been determined. There is no research to prove whether taking this proct will affect the patient's driving and operating the machine. However, studies have proved that this proct may cause fatigue. If this happens, the patient should be told to drive and operate the machine carefully

The pharmacokinetics of pemetrexed was evaluated in 426 patients with various tumor types. The patients were treated with single drug at a dose of 0.2-838 mg / m2, intravenously for 10 minutes. Pemetrexed was mainly excreted from the urinary tract in the form of technical drug. Within 24 hours after administration, 70% - 90% of pemetrexed was excreted from the urine in the form of technical drug. The overall clearance rate of pemetrexed was 91.8 ml / min (creatinine clearance rate was 90 mL / min). For patients with normal renal function, the half-life in vivo was 3.5 hours; With the decrease of renal function, the clearance rate will decrease, but the dose in vivo will increase. With the increase of pemetrexed dose, AUC and Cmax increased in proportion. Multi cycle treatment did not change the pharmacokinetic parameters of pemetrexed. Pemetrexed showed a steady-state distribution with a volume of 16.1 L. In vitro studies showed that the plasma protein binding rate of pemetrexed was about 81%, and it was not affected by renal function. The pharmacokinetic study of pemetrexed in special population was a single group study in a total of 400 patients. In the elderly - there was no significant change in the pharmacokinetics of pemetrexed in the population aged 26-80 years. Children - children were not included in the clinical study. There was no difference in the pharmacokinetics of pemetrexed between male and female patients. The pharmacokinetics of pemetrexed was similar in ethnic Caucasian and African patients. There have been studies on the pharmacokinetics of Japanese patients. Although there is no statistical comparison report on the pharmacokinetic parameters between Japanese patients and Western patients, it still shows that the absolute dose parameters of the two patients are basically similar, and there is no significant clinical difference. The increase of AST, SGOT, alt, SGPT and TBIL did not affect the pharmacokinetics of pemetrexed. However, no pharmacokinetic study was concted in patients with liver damage See "patients with liver dysfunction" under [precautions]). Renal insufficiency - the pharmacokinetics of pemetrexed was studied in 127 patients with renal insufficiency. If combined with cisplatin treatment, the plasma clearance rate of pemetrexed decreased and the systemic exposure dose increased with the decrease of renal function. When the creatinine clearance rates were 45, 50 and 80 ml / min, the total body exposure (AUC) increased by 65%, 54% and 13%, respectively Refer to the "warning" section under [usage and dosage] and [precautions]

Malignant pleural mesothelioma - efficacy and safety of cisplatin plus cisplatin in the first-line treatment of malignant pleural mesothelioma: a single blind, randomized, multicenter clinical study to compare the survival time of cisplatin plus cisplatin and cisplatin alone in the treatment of malignant pleural mesothelioma. A total of 448 patients were enrolled in the study. The drug was given intravenously at 500mg / m2 for 10 minutes, and cisplatin was given at 75mg / m2 for at least 2 hours 30 minutes after the drug administration. The two drugs were administered on the first day of each cycle, once every 21 days. After 117 patients were enrolled in the study, they had leukocyte and gastrointestinal adverse reactions, so they changed the regimen and were given folic acid and vitamin B12 supplement treatment at the same time. All randomized and treated patients were included in the analysis of the main study end point, and patients who received folic acid and vitamin B12 supplement treatment (supplement treatment is recommended, see usage and dosage section) throughout the study were also analyzed. The results of all patients were similar to those of patients who received full dose of supplemental therapy. The general situation of all patients is shown in Table 1. Table 2 shows the survival outcomes of all patients who were randomized and treated, as well as those who received vitamin supplementation from the time of enrollment. A total of 303 patients were confirmed as malignant pleural mesothelioma by histology. There was no significant difference between the above 65 years old group and the under 65 years old group. Because of the small number of non white patients enrolled, racial differences were not seen in the study. The difference of median survival time between female patients in combination group and monotherapy group (15.7 months vs. 7.5 months) was larger than that of male patients (November combination group vs. 9.4 months monotherapy group). It is impossible to determine whether the difference is caused by objective reasons. It is difficult to evaluate the efficacy of drugs in the treatment of malignant pleural mesothelioma. However, according to the existing evaluation criteria, the effective rate of this drug combined with cisplatin in the treatment of malignant pleural mesothelioma is better than that of single drug cisplatin, and the combined treatment can also improve lung function better than single drug group. The tolerance of patients receiving full folic acid and vitamin B12 supplementation was further analyzed. It can be seen that the median treatment cycle of the combination group (168 cases) was 6, while that of the cisplatin monotherapy group (163 cases) was 4. However, compared with the patients who did not receive full folic acid and vitamin B12 supplementation, the median treatment cycle of the latter group was 2 cycles in both the combined treatment group (32 cases) and the single drug group (38 cases). In the combined treatment group, the relative dose intensity of the drug was 93% (compared with the required dose), and the relative dose intensity of cisplatin was 94%; The dose intensity of cisplatin group was 96%. Objective to evaluate the safety and efficacy of pemetrexed in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after chemotherapy. Randomized clinical study: an international multicenter, randomized, open phase 3 clinical study comparing the overall survival after pemetrexed and docetaxel treatment. Pemetrexed was administered at a dose of 500 mg / m2, intravenously within 10 minutes; The dose of paclitaxel was 75 mg / m2, which was infused intravenously within 1 hour. Both drugs were administered on the first day of a 21 day course of treatment. All patients treated with pemetrexed received folic acid and vitamin B12 supplementation. The purpose of this study was to obtain that the overall survival of pemetrexed group was better or not worse than that of paclitaxel group. The general data of the enrolled patients are shown in Table 3. The primary endpoint was overall survival. The median survival time of pemetrexed group was 8.3 months, and that of paclitaxel group was 7.9 months. The risk ratio (HR) was 0.99 (see Table 4). The study did not show a higher overall survival in the pemetrexed group. The efficacy of pemetrexed group was not inferior to that of docetaxel group, and it was not confirmed, because the data of previous studies could not be used to evaluate the reliable and continuous survival impact of docetaxel treatment, and the cross treatment in the progression of disease may also affect the survival of patients. According to the response rate of tumor treatment (a confirmed alternative endpoint), the effect of pemetrexed on survival was consistent with that of docetaxel. The results showed that there was no significant difference between pemetrexed and paclitaxel in the survival time of patients aged 65 or above. Only a very small number of non white people participated in the assessment of possible inter person differences. After predictor correction, there was no difference in survival between pemetrexed group and paclitaxel group. The second endpoint included objective response rate, progression free survival (PES) and time to disease progression (ttpd). There was no significant difference between pemetrexed and docetaxel in objective response rate, progression free survival and disease progression time

The pharmacokinetic study of pemetrexed in special population was a single group study in a total of 400 patients< There was no significant change in the pharmacokinetics of pemetrexed in the aged 26-80
children - children were not included in the clinical study
there was no difference in the pharmacokinetics of pemetrexed between male and female patients
the pharmacokinetics of pemetrexed was similar in Caucasian and African patients. There have been studies on the pharmacokinetics of Japanese patients. Although there is no statistical comparison report on the pharmacokinetic parameters between Japanese patients and Western patients, it still shows that the absolute dose parameters of the two patients are basically similar, and there is no significant clinical difference
liver dysfunction - elevated ast, SGOT, alt, SGPT and total bilirubin did not affect the pharmacokinetics of pemetrexed. However, no pharmacokinetic study was concted in patients with liver damage Please refer to the part of patients with liver dysfunction under [precautions]
renal insufficiency - the pharmacokinetics of pemetrexed was studied in 127 patients with renal insufficiency. If combined with cisplatin treatment, the plasma clearance rate of pemetrexed decreased and the systemic exposure dose increased with the decrease of renal function. When the creatinine clearance rates were 45, 50 and 80 ml / min, the total body exposure (AUC) increased by 65%, 54% and 13%, respectively Refer to the warning section under [usage and dosage] and [precautions]
warning
patients with reced renal function
this proct is mainly excluded from the body in the form of technical drug through the urinary tract. If the creatinine clearance rate is more than or equal to 45ml / min, no dose adjustment is needed. For creatinine clearance & lt; There was not enough research data of patients to give the recommended dose. Therefore, for creatinine clearance rate & lt; 45 ml / min patients should not be given this proct treatment Refer to the recommended dosage adjustment method in usage and dosage
in the clinical study, a patient with severe renal insufficiency (creatinine clearance rate: 19mL / min) died of drug-related toxicity after receiving single drug treatment without folic acid and vitamin B12 supplementation
precautions
general precautions
this proct should be used under the guidance of a qualified doctor with anti-tumor drug application experience. It should be treated in medical institutions with sufficient diagnosis and treatment technology, which can also ensure the timely treatment of complications. The treatment-related adverse reactions seen in clinical studies can be recovered. Patients who were not pretreated with corticosteroid before administration were prone to skin rash. Pretreatment with dexamethasone (or similar drugs) can rece the incidence and severity of skin reactions See [usage and dosage]
it is unclear whether this proct causes retention of body fluids, such as pleural effusion or ascites. For patients with body fluid retention with obvious clinical symptoms, drainage of body cavity effusion before medication can be considered
laboratory examination
all patients who are ready to receive the treatment of this proct need to complete blood cell examination including platelet count and blood biochemical examination, and monitor the lowest point and recovery of blood cells after administration. The above items need to be checked at the beginning of each cycle, the 8th day and the 15th day of the clinical study. Patients need neutrophils ≥ 1500 / mm3, platelets ≥ 1000000 cells / mm3, creatinine clearance rate ≥ 45ml / min before starting the treatment
patients with liver dysfunction
bilirubin & gt; Patients with 1.5 times normal upper limit were not included in the clinical study: patients without liver metastasis, if transaminase & gt; 3.0 times the upper limit of normal, not included in the clinical study; Patients with liver metastasis, if the transaminase is between 3.0 and 5.0 times the upper limit of normal, will be included in the clinical study
the dose adjustment of patients with liver dysfunction is shown in Table 2 Refer to the special population section under pharmacokinetics)
patients with renal insufficiency
this proct is mainly excreted through the kidney. Compared with patients with normal renal function. The overall clearance rate decreased and AUC increased in patients with renal insufficiency. In patients with moderate renal insufficiency, the safety of cisplatin combined with this proct has not been determined (see special population section under [pharmacokinetics])
the interaction between the drug and laboratory tests has not been determined
there is no research to prove whether taking this proct will affect the patient's driving and operating the machine, however, it has been proved that this proct may cause fatigue. If this happens, the patient should be told to drive and operate the machine carefully
[medication for pregnant and lactating women]
pregnancy: pregnant women receiving this drug may be harmful to the fetus. Pemetrexed 0.2 mg / kg (0.6 mg / m2) or 5 mg / kg (15 mg / m2) was given intravenously to pregnant mice from 6 to 15 days of gestation, which had fetal toxicity and teratogenicity. Pemetrexed at a dose of 0.2 mg / kg (about 1 / 833 of the human recommended dose) can cause fetal malformation (incomplete ossification of talus and skull), and cleft palate at a dose of 5 mg / kg (equivalent to 1 / 33 of the human recommended dose). Embryo toxicity is mainly manifested in the increase of embryo mortality and the retardation of embryo development. There are no studies on pregnant women receiving this proct because contraception is recommended. If the patient who used this proct ring pregnancy is pregnant ring the use of this proct, the potential risk to the fetus should be informed
lactation: whether this proct or its metabolites can be secreted from milk remains to be determined. However, this proct may have potential serious harm to infants, and mothers receiving this proct should stop breastfeeding
[medication for children]
the safety and effectiveness of medication for children have not been determined
[medication for elderly patients]
according to the dose adjustment method of all patients, no special protocol is needed (see the special population section of [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 vitamin B12 did not change the pharmacokinetics of pemetrexed
the effect of cytochrome P450 enzyme on drug metabolism in vitro prediction of liver microglobulin showed that pemetrexed did not rece drug clearance through CYP3A enzyme, CYP2D6 enzyme, CYP2C9 enzyme and CYP1A2 enzyme metabolism. No study was concted to observe the effect of pemetrexed on cytochrome P450 isozymes. Because, according to the recommended administration schele (once every 21 days), this proct has no obvious inction effect on any enzyme
aspirin - low to moderate doses (325mg / 6h) of aspirin did not affect the pharmacokinetics of pemetrexed, while the effect of high doses of aspirin on the pharmacokinetics of pemetrexed remains unclear
ibuprofen - in patients with normal renal function, ibuprofen 400 mg daily, 4 times a day, can rece 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
the proct is mainly excreted from the urinary tract in the form of technical drug through glomerular filtration and renal tubular excretion. At the same time, administration of drugs harmful to the kidney may delay the clearance of this proct, while administration of other drugs (such as probenecid) that increase the burden of renal tubules may also delay the clearance of this proct
[drug overdose]
only a few cases of drug overdose were reported. The main adverse reactions reported were neutropenia, anemia, thrombocytopenia, mucositis and rash. The major complications of drug overdose were myelosuppression, including neutropenia, thrombocytopenia and anemia. In addition, infection, diarrhea and mucositis with or without fever may occur. In case of drug overdose, appropriate medical measures should be taken immediately under the guidance of doctors
in clinical studies, formyltetrahydrofolate can be used in patients with grade 4 leukopenia or grade 4 neutropenia for more than 3 days. Formyltetrahydrofolate should be used immediately in patients with grade 4 thrombocytopenia or grade 3 thrombocytopenia related bleeding or grade 3 / 4 mucositis. The recommended dosage and method of formyltetrahydrofolate is: intravenous administration, the first dose is 100mg / m2, then 50mg / m2, once every 6 hours for 8 days
the role of dialysis in relieving the overdose has not been determined
[Specification] 0.5g/bottle
[storage]
this proct should be stored at room temperature
the solution prepared according to the above method does not contain antibacterial preservatives, so it should be used immediately from the point of view of microorganism, without partial discarding. If it is not used up at one time, the prepared solution can be stored in refrigerator (2-8 ℃) or room temperature (15-30 ℃), without avoiding light. Its physical and chemical properties remain stable within 24 hours
this proct has no photosensitivity
[package] glass bottle, 1 bottle and 1 box
[validity period] 24 months
[registration number of imported drug] h20050441