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Anzatax is used to treat metastatic ovarian cancer when conventional therapies with anthracycline and platinum have failed or are contraindicated.
1. What is Anzatax?
Anzatax has the main ingredient Anzatax, which belongs to the taxan group of anti-cancer drugs. The drug is prepared in the form of a concentrated solution for injection:Anzatax medicine 6mg/ml; The 5ml vial contains 30 mg of Anzatax; 16.7ml vial contains Anzatax 100mg; The 25ml bottle contains Anzatax 150mg. Anzatax is an ETC prescription drug indicated for use in the following cases:
Carcinoma of the ovary : In the first chemotherapy of ovarian cancer, Anzatax is indicated for the treatment of patients with cancer. advanced or residual disease (>1 cm) after initial laparotomy, in combination with cisplatin. In the treatment of ovarian cancer with second-line chemotherapy, Anzatax is indicated for the treatment of metastatic carcinoma of the ovary after substandard, platinum-containing therapy.
Breast Carcinoma: In adjuvant therapy, Anzatax is indicated for the treatment of patients with node-positive breast carcinoma following anthracycline and cyclophosphamide (AC) therapy. Adjuvant therapy with Anzatax should be considered as an alternative to prolonged AC therapy.
Advanced Non-Small Cell Lung Carcinoma: Anzatax, in combination with Cisplatin, is indicated for the treatment of non-small cell lung carcinoma (NSCLC) in non-small cell lung cancer patients. surgery and/or radiation therapy.
AIDS-related Kaposi's sarcoma: Anzatax is indicated for the treatment of patients with advanced AIDS-related Kaposi's sarcoma (KS) who have failed prior liposomal anthracycline therapy.
2. Pharmacodynamics of Anzatax
Anzatax is a novel antimicrobial agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing degradation. This stabilization leads to inhibition of the normal dynamic reorganization of the microtubule network required for important interphase and mitotic cell functions. In addition, Anzatax causes abnormal plaques or "bundles" of microtubules throughout the cell cycle and numerous microtubule vacancies during mitosis.
After intravenous administration of Anzatax, Anzatax plasma concentrations decrease in two phases. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The latter is partly due to the relatively slow flow of Anzatax from the peripheral compartment.
3. Pharmacokinetics of Anzatax
After intravenous administration, Anzatax reduces plasma drug concentrations in 2 phases. The pharmacokinetics of Anzatax were determined 3 and 24 h after infusion at doses of 135 and 175 mg/m 2 . The estimated mean terminal half-life ranged from 3.0 to 52.7 hours, and the mean, non-compartment, values for total body clearance ranged from 11.6 to 24.0 l / hour / m 2 ; Total body clearance appears to decrease with higher plasma concentrations of Anzatax. The mean steady-state volume of distribution ranges from 198 to 688 l/m2, indicating extensive extravascular and/or tissue-associated distribution. During a 3-hour infusion, the dose is gradually increased leading to non-linear pharmacokinetics. For a 30% increase in dose from 135 mg/m2 to 175 mg/m2, the Cmax and AUC → ∞ values increased by 75% and 81%, respectively.
Inpatient variation in systemic Anzatax exposure is minimal. There is no evidence of accumulation of Anzatax with multiple courses of treatment.
In vitro studies of binding to human serum proteins indicate that 89-98% of the medicinal product is bound. The presence of cimetidine, ranitidine, dexamethasone or diphenhydramine did not affect the protein binding of Anzatax.
In clinical trials with concomitant administration of Anzatax and doxorubicin, the distribution and elimination of doxorubicin and its metabolites were prolonged. Total plasma exposure to doxorubicin was 30% higher when Anzatax was immediately following doxorubicin than when there was a 24-hour interval between the medicinal products.
4. Contraindications of the drug Anzatax
Patients who are allergic to any ingredient or excipients of Anzatax; Anzatax should not be used in patients with solid tumors with baseline neutrophil counts <1,500 cells/mm3, or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts. <1,000 cells/mm 3; Anzatax is contraindicated during lactation; Contraindicated in patients with concomitant, severe, uncontrolled infections. 5. Side effects of the drug Anzatax Hypersensitivity to the ingredients of the drug: Serious hypersensitivity reactions with Anzatax treatment patients account for 2% even though they have been prepared with antihistamines, corticosteroids and other drugs. H2 receptor antagonists. Hematology: Anzatax causes dose-limiting toxicity that is bone marrow suppression. The most common hematologic adverse reaction was neutropenia. Therefore, regular monitoring of blood counts is required during treatment with Anzatax. Infections: The most common are upper respiratory tract infections, blood and urinary tract infections. Neurology: There have been few cases of severe neurological symptoms, usually in patients receiving high doses of Anzatax. Symptoms worsened when the patient was reintroduced Anzatax. A 20% dose reduction is required for patients with peripheral neuropathy. Cardiovascular system: Anzatax infusion-induced hypotension was observed in 25% of patients and bradycardia in 12% of patients. Most heart problems have no symptoms and often require no treatment. However, severe hypersensitivity reactions often lead to severe hypotensive effects and require therapeutic measures. Clinical signs should be regularly monitored, especially during the first hour of infusion. Liver: An increase in liver enzymes has been observed in the majority of patients with normal liver function treated with Anzatax. Anzatax must be used with caution in patients with impaired liver function. Joint and muscle pain. Digestive system: Vomiting (53%), diarrhea (26%) and mucositis (26%). There have been several cases of intestinal perforation during treatment with Paciitaxel. Caution must be exercised to eliminate this risk when a patient receiving Anzatax presents with abdominal pain. Injection site reactions: Phlebitis may occur following the infusion of Anzatax. Other reactions: Temporary changes in nails and skin, hair loss.
6. Drug interactions
The recommended regimen for Anzatax for first-line chemotherapy of ovarian carcinoma is to administer Anzatax before cisplatin. Patients treated with Cisplatin and Anzatax may have an increased risk of renal failure compared with Cisplatin alone in gynecological cancer. When Anzatax and Doxorubicin are administered close to each other, because the elimination of Doxorubicin and its active metabolites may be reduced, Anzatax should be used for the initial treatment of metastatic breast cancer 24 hours after doxorubicin administration. . The metabolism of Anzatax is catalyzed in part by the cytochrome P450 isoenzymes CYP3A4 and CYP2C8. Therefore, in the absence of PK drug-drug interaction studies, caution should be exercised when Anzatax is co-administered with inhibitors of CYP2C8 or CYP3A4 because Anzatax toxicity may be increased by higher Anzatax exposure. Co-administration of Anzatax with inducers of CYP3A4 or CYP2C8 is not recommended as the efficacy of the above agents may be reduced by lower Anzatax exposure. Studies in KS patients, who were receiving multiple concomitant medications, showed that the systemic clearance of Anzatax was significantly lower in the presence of nelfinavir and ritonavir, but not with Indinavir. There is insufficient information on interactions with other protease inhibitors. Therefore, Anzatax should be used with caution in patients receiving protease inhibitors as concomitant therapy. Anzatax therapy should not be given to patients with a basal neutrophil count less than 1,500 cells/mm3. For patients with advanced HIV disease and low-risk AIDS-related Kaposi's sarcoma, Anzatax, at the dose recommended for this disease, may be initiated and repeated if the neutrophil count is at least 1,000 cells/mm 3. Hypotension, bradycardia, and hypertension have been reported with Anzatax, but no treatment was generally required. Occasionally, Anzatax infusion must be interrupted or discontinued because of initial or recurrent hypertension. Vital signs should be monitored frequently, especially during the first hour of Anzatax infusion. There is no need for continuous cardiac monitoring except in patients with severe conduction abnormalities. Although the occurrence of peripheral neuropathy is frequent, the development of serious symptoms is unusual and a 20% dose reduction is required for all subsequent courses of Anzatax. Anzatax contains USP dehydrated alcohol, 396 mg/mL; Possible CNS and other effects of alcohol should be considered. Because of the possibility of extravasation, the infusion site should be closely monitored for possible penetration during administration. Patients must be pretreated with corticosteroids, H2 blockers, and antihistamines. Significant hypersensitivity reactions characterized by dyspnea and therapeutic hypotension, angioedema, and generalized urticaria have occurred in <1% of patients receiving Anzatax after adequate therapy. These reactions are probably histamine-mediated. In the event of a severe hypersensitivity reaction, Anzatax infusion should be discontinued immediately, symptomatic treatment should be initiated and the patient not continued with the medicinal product. Bone marrow suppression (primarily neutropenia) is dose-limiting toxicity. Regular monitoring of blood counts is required. Patients with hepatic impairment may be at increased risk of toxicity, especially grade 3 -4 myelosuppression. There have been no reports of increased toxicity of Anzatax following a 3-hour infusion in patients with mildly abnormal liver function. With longer infusions of Anzatax, an increase in myelosuppression may be observed in patients with moderate to severe hepatic impairment. Serious cardiac conduction abnormalities have rarely been reported with Anzatax alone. If a patient develops significant cardiac conduction abnormalities while receiving Anzatax, appropriate therapy and continuous cardiac monitoring should be instituted during subsequent treatment with Anzatax. When using Anzatax in combination with Doxorubicin or Trastuzumab for the initial treatment of metastatic breast cancer, attention should be paid to monitoring cardiac function. When patients are in need of treatment with Anzatax in these combinations, a baseline cardiac evaluation including history, physical examination, electrocardiogram, echocardiography and/or MUGA should be performed. If treatment with Anzatax is continued, cardiac function should be monitored more frequently (eg, every 1-2 cycles). Anzatax has been shown to be teratogenic, embryotoxic and mutagenic in multiple experimental systems. Therefore, sexually active male and female patients should use effective methods of contraception during and for 6 months after treatment for men and women. Hormonal contraception is contraindicated in hormone receptor-positive tumors.
7. How to use Anzatax effectively?
How to use Anzatax:
Anzatax is recommended to be used only by intravenous infusion. Do not use the drug injected into the spinal cord, peritoneum or pleura. Anzatax must be diluted prior to intravenous infusion with 0.9% NaCl or 5% Glucose solution. The solution after dilution of the drug has a final concentration of 0.3-1.2mg/ml. After dilution of Anzatax solution bottle, it should be rotated slightly to evenly disperse Paclitaxel. Absolutely do not shake. Avoid contact of Anzatax solution with lines, tools or machinery made of PVC with plasticizers while preparing the infusion. Prepare and store the diluted solution of Paclitaxel in a glass stoppered bottle. Paclitaxel solution must be infused on a polyethylene-coated line using a dedicated IMED pump. Although the Anzatax solution prepared with the above dosage is chemically stable for 48 hours at room temperature, the reconstituted solution must be used immediately as it does not contain antibacterial agents. An infusion of Anzatax solution must be done within 24 hours of dilution and unused portion should be discarded according to the instructions. All patients must be prescribed medication by qualified physicians. Before each treatment cycle, patients need to be taken with the following drugs:
Dexamethasone 20mg orally 12 hours before and 6 hours before the start of Anzatax infusion. Promethazine 25 or 50 mg or other suitable H1 antagonist administered intravenously 30 minutes before the initiation of the Anzatax infusion. Ranitidine 50mg or Cimetidine 300mg intravenous infusion over 15 minutes, 30 minutes before starting Anzatax infusion. For ovarian cancer patients, Anzatax is indicated at a dose of 175 mg/m2, intravenous infusion continuously for 3 hours, followed by Cisplatin 75 mg/m2. The infusion MUST be repeated every 3 weeks. For the treatment of metastatic ovarian cancer or metastatic breast cancer, Paclitaxel is prescribed as a single dose of 175 mg/m2 intravenously over 3 hours. The intravenous infusion should be repeated every 3 weeks if the drug is tolerated. Patients tolerated up to 9 cycles of Paclitaxel, but the optimal course of treatment has not been determined. For the treatment of secondary or primary non-small cell lung cancer, the recommended dose of Paclitaxel is 175 mg/m2 intravenously over 3 hours followed by Cisplatin 80 mg/m2 skin, at intervals between doses. is 3 weeks. For the treatment of lymph node-positive breast cancer, the recommended dose of Paclitaxel is 175 mg/m2 intravenously over 3 hours at 3-week intervals for 4 courses following the combination of doxorubicin and cyclophosphamide. Repeat treatment with Paclitaxel only when the patient has a minimum neutrophil count of 1.5 X 109 cells/L and a minimum platelet count of 100 X 109 cells/L. If severe neutropenia (neutrophil count less than 0.5 X 109 cells/L for 7 days or more) or severe peripheral neuropathy occurs during treatment with Paclitaxel, Paclitaxel dose should be reduced by 20% in subsequent courses.
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