Pemetrexed Disodium for Injection

Pemetrexed is an antifolate preparation with a core pyrrolopyrimidine group in its structure. It inhibits cell replication and thus tumor growth by destroying the normal metabolic process of intracellular folate dependence. In vitro studies have shown that pemetrexed can inhibit the activity of thymidylate synthase, dihydrofolate reductase and glycinamide nucleotide formyltransferase, which are enzymes necessary for the synthesis of folate and participate in the bioresynthesis of thymine nucleotides and purine nucleotides. Pemetrexed enters the cell through the carrier carrying folic acid and the folate binding protein transport system on the cell membrane. Once pemetrexed enters the cell, it is converted into polyglutamate under the action of folylpolyglutamate synthetase. Polyglutamate remains in the cell and becomes an inhibitor of thymidylate synthase and glycinamide nucleotide formyltransferase. Polyglutamate is a time-concentration dependent process in tumor cells, while the concentration in normal tissues is very low. The half-life of polyglutamate metabolites in tumor cells is prolonged, thereby prolonging the action time of the drug in tumor cells. Preclinical studies have shown that pemetrexed can inhibit the growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) in vitro. Studies on the mesothelioma cell line MSTO-211H have shown that pemetrexed combined with cisplatin has a synergistic effect.

The main ingredient of this product is pemetrexed disodium, and the auxiliary ingredient is mannitol.

This product is off-white to slightly yellow loose lumps or powder.

Indicated for combination with cisplatin for the treatment of inoperable malignant pleural mesothelioma.

The recommended dose of pemetrexed combined with cisplatin for the treatment of malignant pleural mesothelioma is 500 mg/m2 every 21 days, infused over 10 minutes. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours. Cisplatin infusion should be given 30 minutes after the end of pemetrexed administration. A hydration plan is required for cisplatin treatment. For details, please refer to the cisplatin instructions. Pre-medication: Corticosteroids - Patients who have not taken corticosteroids beforehand have a higher incidence of rash when using pemetrexed. Pre-medication with dexamethasone (or similar drugs) can reduce the incidence and severity of skin reactions. Dosage: Dexamethasone 4 mg orally twice a day, 1 day before, on the day of, and 1 day after pemetrexed administration for 3 consecutive days. Vitamin supplementation

The following table lists the statistical results of the frequency and severity of adverse reactions greater than 5% in 168 patients with malignant pleural mesothelioma who were randomized to receive pemetrexed and cisplatin combination therapy and 163 patients with malignant pleural mesothelioma who received cisplatin alone in clinical studies. In both trial groups, patients who had not previously received chemotherapy were supplemented with adequate folic acid and vitamin B12. System Organ Frequency Events Pemetrexed/Cisplatin Cisplatin (N=168) (N=163) All % 3-4 degree % All % 3-4 degree % Blood and lymphatic system abnormalities Very common Neutrophils 56.0 23.2 13.5 3.1 White blood cells 53.0 14.9 16.60.6 Hemoglobin 26.24.2 10.40.0 Platelets 23.25.4 8.60.0 Eye abnormalities Common Conjunctivitis 5.40.0 0.60.0 Gastrointestinal abnormalities Very common Nausea 82.1 11.9 76.75.5 Vomiting 56.5 10.7 49.74.3 Stomatitis/pharyngitis 23.23.0 6.10.0 Anorexia 20.21.2 14.10.6 Diarrhea 16.7 3.6 8.0 0.0 Constipation 11.9 0.6 7.4 0.6 Common Indigestion 5.4 0.6 0.6 0.0 General abnormalities Very common Fatigue 47.6 10.1 4 2.3 9.2 Metabolism Nutrition abnormalities Common Dehydration 6.5 4.2 0.6 0.6 Nervous system abnormalities Very common Nervous/sensory 10.1 0.0 9.8 0.6 Common Taste disturbance 7.7 0.0 6.10.6 Renal abnormalities Very common Decreased creatinine clearance 10.7 0.6 9.8 1.2 Renal/urinary system disorders 16.7 0.6 18.4 2.5 Skin and subcutaneous tissue abnormalities Very common Rash 16.1 0.6 4.9 0.0 Hair loss 11.3 0.0 5.5 0.0 * For the classification of adverse reactions, please refer to NCICTC version 2.0. Very common refers to ge; 10%; Common refers to 5% and 10%. (The incidence of all adverse reactions listed in this table has been reduced by 5% to exclude the possibility that the investigators may be subjectively related to pemetrexed and cisplatin.) Clinically relevant toxic reactions with an incidence between 1% and 5% (including 5%) in patients randomized to pemetrexed and cisplatin included: increased AST, ALT and GGT, infection, fever, neutropenic fever, renal failure, chest pain and urticaria; clinically relevant toxic reactions with an incidence of 1% included arrhythmia and motor neuron disease. The following table lists the statistical results of the frequency and severity of adverse reactions greater than 5% in 265 patients randomized to pemetrexed monotherapy and folic acid and vitamin B12 supplementation and 276 patients receiving docetaxel monotherapy in clinical studies. In both trial groups, they were diagnosed with locally advanced or metastatic non-small cell lung cancer. They had received previous chemotherapy. System Organ Frequency Events Pemetrexed/Cisplatin Cisplatin N=265 N=276 All % 3-4 degree % All % 3-4 degree % Blood and lymphatic system abnormalities Very common Hemoglobin 19.24.222.14.3 Leukocytes 12.14.234.127.2 Neutrophils/Granulocytes 10.95.345.340.2 Common Platelets 8.31.91.10.4 Gastrointestinal abnormalities Very common Nausea 30.92.616.71.8 Anorexia 21.91.923.92.5 Vomiting 16.21.512.01.1 Stomatitis/Pharyngitis 14.71.117.4 1.1 Diarrhea 12.80.424.32.5 Common Constipation 5.70.04.00.0 General Abnormality Very Common Fatigue 34.05.335.95.4 Common Fever 8.30.07.60.0 Hepatobiliary Abnormality Common SGPT (ALT) 7.91.91.40.0 SGOT (AST) 6.81.10.70.0 Skin and Subcutaneous Tissue Abnormality Very Common Rash/Desquamation 14.00.06.20.0 Common Itch 6.80.41.80.0 Hair Loss 6.40.437.72.2 bull; Adverse reaction grading refers to NCICTC 2.0 version. Very common refers to ge; 10%; Common refers to 5% and 10%. (The incidence of all adverse reactions listed in this table is reduced by 5% to exclude the possibility that the researchers subjectively believe that it may be related to pemetrexed). Clinically relevant toxicities occurring in 1% and 5% of patients randomized to pemetrexed included: neuropathy, motor neuron disease, abdominal pain, increased creatinine, febrile neutropenia, infection without neutropenia, allergic reaction/anaphylaxis, and erythema multiforme; clinically relevant toxicities occurring in 1% or 1% of patients randomized to pemetrexed included supraventricular arrhythmia. The incidence of grade 3 and 4 laboratory toxicities in the three integrated phase 2 studies of pemetrexed alone (n = 164) was similar to that in the phase 3 studies of pemetrexed alone listed above, except for the incidence of neutropenia (12.8% and 5.3%, respectively) and elevated alanine aminotransferase (15.2% and 1.9%, respectively), which was primarily due to differences in the study population, as the phase 2 studies included patients with breast cancer who had liver metastases and/or abnormal baseline liver function tests, some of whom had not been previously treated with chemotherapy and some of whom had been heavily treated with chemotherapy.

It is contraindicated in patients with a history of severe allergic reaction to pemetrexed or other ingredients of the drug.

Chemotherapeutic drugs--Cisplatin does not change the pharmacokinetics of pemetrexed, and pemetrexed has no effect on the pharmacokinetics of all platinum drugs. Vitamins--Concurrent administration of oral folic acid and intramuscular vitamin B12 does not change the pharmacokinetics of pemetrexed. Cytochrome P450 enzymes on drug metabolism--In vitro studies on liver microsomal proteins showed that pemetrexed did not lead to a decrease in the clearance of drugs metabolized by CYP3A enzymes, CYP2D6 enzymes, CYP2C9 enzymes, and CYP1A2 enzymes. No studies have been conducted to observe the effects of pemetrexed on cytochrome P450 isoenzymes. Because, if the recommended dosing schedule (once every 21 days) is followed, pemetrexed has no significant induction effect on any enzyme. Aspirin

Sealed, stored in a cool, dark and dry place (avoid light and not exceed 20°C). Valid for 18 months.

0.5g (based on pemetrexed)

Nanjing Pharmaceutical FACTORY Co., Ltd.

• Founded in:

  1991-07-11

• Address:

  No. 26, Xingang Avenue, Nanjing Economic and Technological Development Zone

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  91320192134908655F

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  200.8 million yuan

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