1, drug introduction
Composition:
Tratuzumab。
Dosage form: injection
Shape: Each bottle of the drug contains 440mg concentrated trastuzumab powder, which is white to light yellow freeze-dried powder.
2. Functional indications
It is suitable for the treatment of metastatic breast cancer with overexpression of HER2. 1. Accept 1 or more chemotherapy regimens as monotherapy for metastatic breast cancer. 2. Combined with taxanes to treat metastatic breast cancer without chemotherapy.
Specifications/Chinese and Western medicines:
440 mg (20 ml)/bottle
3. Usage and dosage
Initial loading dose: It is suggested that the initial loading dose of Herceptin is 4mg/kg. Intravenous infusion within 90 minutes. Maintenance dose: It is suggested that the weekly dose of Herceptin is 2mg/kg. If the initial load can be tolerated, the dose can be administered within 30 minutes and can be used until the disease progresses. According to the data of foreign market survey, the patients who received treatment used it continuously for about 24 to 26 weeks on average.
4. Adverse reactions
All the data of adverse events came from clinical trials, and the drug was used alone or in combination with chemotherapy drugs (anthracyclines [adriamycin or epirubicin] plus cyclophosphamide or paclitaxel) according to the recommended dose. For metastatic cancer patients with overexpression of HER2, Herceptin is used alone for patients who failed to receive 1 or more chemotherapy schemes. In 2 13 patients, the incidence of the following adverse reactions was ≥ 5%: overall, abdominal pain, accidental injury, fatigue, back pain, chest pain, chills, fever, cold-like symptoms, headache, infection, neck pain and pain. Cardiovascular: vasodilation. Digestion: anorexia, constipation, diarrhea, indigestion, flatulence, vomiting and nausea. Metabolism: peripheral edema, edema. Musculoskeletal: joint pain, muscle pain. Nervous system: anxiety, depression, dizziness, insomnia, abnormal sensation, drowsiness. Breathing: asthma, aggravated cough, dyspnea, nosebleeds, lung diseases, pleural effusion, pharyngitis, rhinitis and sinusitis. Skin: itching, rash.
Taboo:
Patients who are allergic to trastuzumab or other ingredients are prohibited from using it.
5. Preventive measures
The treatment of this drug must be started under the supervision of a doctor who is experienced in treating cancer. Symptoms and signs of cardiac dysfunction, such as dyspnea, aggravated cough, paroxysmal dyspnea at night, peripheral edema, S3 galloping or decreased ejection fraction, were observed in patients treated with this drug. Congestive heart failure associated with Herceptin treatment may be quite serious, which may lead to fatal heart failure, death and cerebral embolism with mucinous embolus. Especially in patients with metastatic breast cancer treated with Herceptin combined with anthracycline (adriamycin or epirubicin) and cyclophosphamide, moderate to severe cardiac insufficiency (NYHA Grade III/IV) was observed. Patients with cardiac insufficiency before treatment need special care. Patients who choose to receive this drug should receive a comprehensive basic cardiac assessment, including medical history, physical examination and one or more of the following tests: EKG, echocardiography and MUGA scan. At present, there is no data to show that there is a suitable evaluation method to determine the risk of cardiac toxicity in patients. During the drug treatment, the left ventricular function should be evaluated frequently. Herceptin should be discontinued if the patient has clinically significant left ventricular dysfunction. Monitoring can't find all patients with cardiac insufficiency. About 2/3 patients with cardiac insufficiency were treated with symptoms, and most of them got better after treatment. Treatment usually includes diuretics, cardiac glycosides and/or angiotensin converting enzyme inhibitors. The vast majority of patients with clinically effective cardiac symptoms and manifestations treated with this drug continue to use Herceptin every week, and no more clinical cardiac conditions will occur. Phenylethanol, as a preservative in sterile water for injection, is toxic to newborns and children under 3 years old. When the drug is used in patients who are known to be allergic to phenylethanol, it should be reconstituted with water for injection.
Pharmacology and Toxicology:
Herceptin is a humanized monoclonal antibody derived from recombinant DNA, which selectively acts on the extracellular site of human epidermal growth factor receptor -2(HER2). It has been observed that 25%-30% patients with primary breast cancer overexpress HER2. Studies have shown that the disease-free survival time of tumor patients with over-expression of HER2 is shorter than that of patients without over-expression. Herceptin? In vitro and animal experiments show that it can inhibit the proliferation of tumor cells that overexpress HER2. In addition, Herceptin is a potential mediator of antibody-dependent cell-mediated cytotoxicity (ADCC). In vitro, herceptin-mediated ADCC has been proved to be more preferentially produced in cancer cells with overexpression of HER2 than in cancer cells without expression of HER2.
Pharmacokinetics:
Drug clearance studies of metastatic breast cancer showed that the pharmacokinetics of 10, 50, 100, 250 and 500mg once a week were dose-dependent. With the increase of dose level, the average half-life is prolonged and the clearance rate is reduced. In clinical trials, the initial loading dose of trastuzumab is 4mg/kg, and the weekly maintenance dose is 2mg/kg. The average half-life was 5.8 days (1-32 days), and the serum concentration of trastuzumab reached a stable state between 16-32 weeks, with an average trough concentration of about 75ug/mL. The effects of pharmacokinetics and patient characteristics (such as age and plasma creatinine concentration) on the distribution of trastuzumab were also evaluated. The data showed that the distribution of trastuzumab in different subgroups of patients did not change.
Medication for pregnant and lactating women:
It was observed that trastuzumab was delivered to the fetus through the placenta in the early stage (20-50 days of pregnancy) and the late stage (20-20-150 days of pregnancy). In view of the fact that the results of animal reproduction research cannot predict human reactions, Herceptin should not be used in pregnant women unless the potential benefits to pregnant women far outweigh the potential risks to the fetus. Lactating women: The breast-feeding cynomolgus monkeys were studied with Herceptin (2mg/kg) at a maintenance dose of 25 times a week. The results showed that Tratuzumab could be secreted into the milk. The existence of trastuzumab in the blood of young monkeys within 3 months after birth has no adverse effect on their growth and development.
Medication for children:
The safety and efficacy of this drug for patients younger than 18 years old have not been determined.