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部分中文维达扎处方资料（仅供参考）
Table 3. Response Rates
A multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML was also carried out. Treatment with subcutaneous Vidaza resulted in a response rate (CR + PR) of 13.9%, using criteria similar to those described above. The mean and median duration of clinical response of PR or better was estimated as 810 and 430 days, respectively; 80% of the responding patients were still in PR or better at the time of completion of study involvement. In another open-label, single-arm study of 48 patients with RAEB, RAEB-T, or AML, treatment with intravenous Vidaza resulted in a response rate of 18.8%, again using criteria similar to those described above. The mean and median duration of clinical response of PR or better was estimated as 389 and 281 days, respectively; 67% of the responding patients were still in PR or better at the time of completion of treatment. Response occurred in all MDS subtypes as well as in patients with adjudicated baseline diagnosis of AML in both of these studies. Vidaza dosage regimens in these 2 studies were similar to the regimen used in the controlled study. Benefit was seen in patients who did not meet the criteria for PR or better, but were considered “improved.” About 24% of Vidaza-treated patients were considered improved, and about 2/3 of those lost transfusion dependence. In the observation group, only 5/83 patients met criteria for improvement; none lost transfusion dependence. In all three studies, about 19% of patients met criteria for improvement with a median duration of 195 days. Response rate estimates were similar regardless of age or gender. INDICATIONS AND USAGE Vidaza is indicated for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. CONTRAINDICATIONS Vidaza is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol. Vidaza is also contraindicated in patients with advanced malignant hepatic tumors. (See PRECAUTIONS). WARNINGS Pregnancy - Teratogenic Effects: Pregnancy Category D Vidaza may cause fetal harm when administered to a pregnant woman. Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single IP (intraperitoneal) injection of 6 mg/m2 (approximately 8% of the recommended human daily dose on a mg/m2 basis) azacitidine on gestation day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation day 15 at doses of ~3-12 mg/m2 (approximately 4%-16% the recommended human daily dose on a mg/m2 basis). In rats, azacitidine was clearly embryotoxic when given IP on gestation days 4-8 (postimplantation) at a dose of 6 mg/m2 (approximately 8% of the recommended human daily dose on a mg/m2 basis), although treatment in the preimplantation period (on gestation days 1-3) had no adverse effect on the embryos. Azacitidine caused multiple fetal abnormalities in rats after a single IP dose of 3 to 12 mg/m2 (approximately 8% the recommended human daily dose on a mg/m2 basis) given on gestation day 9, 10, 11 or 12. In this study azacitidine caused fetal death when administered at 3-12 mg/m2 on gestation days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation day 9. Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities). There are no adequate and well-controlled studies in pregnant women using Vidaza. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Vidaza. Use in Males Men should be advised to not father a child while receiving treatment with Vidaza. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of pre-mating effects of azacitidine exposure on male fertility and embryonic viability.) PRECAUTIONS General Treatment with Vidaza is associated with neutropenia and thrombocytopenia. Complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. After administration of the recommended dosage for the first cycle, dosage for subsequent cycles should be reduced or delayed based on nadir counts and hematologic response as described in DOSAGE AND ADMINISTRATION. Safety and effectiveness of Vidaza in patients with MDS and hepatic or renal impairment have not been studied as these patients were excluded from the clinical trials. Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease. Patients with extensive tumor burden due to metastatic disease have been rarely reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline albumin <30 g/L. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors (See CONTRAINDICATIONS). Renal abnormalities ranging from elevated serum creatinine to renal failure and death have been reported rarely in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for non-MDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to <20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium <3 mEq/L) developed in 5 patients with CML treated with azacitidine and etoposide. If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, the dosage should be reduced or held as described in DOSAGE AND ADMINISTRATION Patients with renal impairment should be closely monitored for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys (see DOSAGE AND ADMINISTRATION section). Information for Patients Patients should inform their physician about any underlying liver or renal disease. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Vidaza. Men should be advised to not father a child while receiving treatment with Vidaza. Laboratory Tests Complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of therapy. Drug Interactions No formal assessments of drug-drug interactions between Vidaza and other agents have been conducted. (See CLINICAL PHARMACOLOGY.) Carcinogenesis, Mutagenesis, Impairment of Fertility The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m2, approximately 8% the recommended human daily dose on a mg/m2 basis) administered IP three times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with azacitidine IP at 2.0 mg/kg (6.0 mg/m2, approximately 8% the recommended human daily dose on a mg/m2 basis) once a week for 50 weeks. A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m2 (approximately 20-80% the recommended human daily dose on a mg/m2 basis) revealed an increased incidence of testicular tumors compared with controls. The mutagenic and clastogenic potential of azacitidine was tested in in vitro bacterial systems Salmonella typhimurium strains TA100 and several strains of trpE8, Escherichia coli strains WP14 Pro, WP3103P, WP3104P, and CC103; in in vitro forward gene mutation assay in mouse lymphoma cells and human lymphoblast cells; and in an in vitro micronucleus assay in mouse L5178Y lymphoma cells and Syrian hamster embryo cells. Azacitidine was mutagenic in bacterial and mammalian cell systems. The clastogenic effect of azacitidine was shown by the induction of micronuclei in L5178Y mouse cells and Syrian hamster embryo cells. Administration of azacitidine to male mice at 9.9 mg/m2 (approximately 9% the recommended human daily dose on a mg/m2 basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development. Treatment of male rats three times per week for 11 or 16 weeks at doses of 15 to 30 mg/m2 (approximately 20-40%, the recommended human daily dose on a mg/m2 basis) resulted in decreased weight of the testes and epididymides, and decreased sperm counts accompanied by decreased pregnancy rates and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m2 resulted in an increase in abnormal embryos in mated females when examined on day 2 of gestation. See WARNINGS. Pregnancy Teratogenic Effects: Pregnancy Category D. See WARNINGS section. Nursing Mothers It is not known whether azacitidine or its metabolites are excreted in human milk. Because of the potential for tumorigenicity shown for azacitidine in animal studies and the potential for serious adverse reactions, women treated with azacitidine should not nurse. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the total number of patients in the three clinical studies described in CLINICAL STUDIES, above, 62 percent were 65 years and older and 21 percent were 75 years and older. No overall differences in effectiveness were observed between these patients and younger patients. In addition there were no relevant differences in the frequency of adverse events observed in patients 65 years and older compared to younger patients. Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function (seeDOSAGE AND ADMINISTRATION section). ADVERSE REACTIONS Overview Adverse Reactions Described in Other Labeling Sections: neutropenia, thrombocytopenia, elevated serum creatinine, renal failure, renal tubular acidosis, hypokalemia, hepatic coma. Most Commonly Occurring Adverse Reactions (SC Route): nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, fatigue, injection site erythema, constipation, neutropenia, ecchymosis. Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (SC Route): Discontinuation: leukopenia (5.0%), thrombocytopenia (3.6%), neutropenia (2.7%). Dose Held: leukopenia (4.5%), neutropenia (4.5%), febrile neutropenia (2.7%). Dose Reduced: leukopenia (4.5%), neutropenia (4.1%), thrombocytopenia (3.2%). Discussion of Adverse Reactions Information The data described below reflect exposure to Vidaza in 268 patients, including 116 exposed for 6 cycles (approximately 6 months) or more and 60 exposed for greater than 12 cycles (approximately one year). Vidaza was studied primarily in supportive care-controlled and uncontrolled trials (n= 150 and n=118, respectively). The population in the subcutaneous studies (n = 220) was 23 to 92 years old (mean 66.4 years), 68% male, and 94% white, and had MDS or AML. The population in the IV study (n = 48) was 35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients received average daily doses between 50 and 100 mg/m2. The following table presents the most common adverse events, whether or not considered drug related by investigators, occurring in at least 5% of patients treated with Vidaza in the supportive care-controlled trial and the uncontrolled subcutaneous trial combined. It is important to note that duration of exposure was longer for the Vidaza-treated group than for the observation group: patients received Vidaza for a mean of 11.4 months while mean time in the observation arm was 6.1 months. Table 4: Most Frequently Observed Adverse Events (≥ 5% in All Vidaza)*
In clinical studies of either SC or IV Vidaza, the following serious treatment-related adverse events occurring at a rate of <5% (not described in Table 4) were reported: Blood and lymphatic system disorders: agranulocytosis, bone marrow depression, splenomegaly. Cardiac disorders: atrial fibrillation, cardiac failure, cardiac failure congestive, cardio-respiratory arrest, congestive cardiomyopathy. Gastrointestinal disorders: diverticulitis, gastrointestinal hemorrhage, melena, perirectal abscess. General disorders and administration site conditions: catheter site hemorrhage, general physical health deterioration, systemic inflammatory response syndrome. Hepatobiliary disorders: cholecystitis. Immune system disorders: anaphylactic shock, hypersensitivity. Infections and infestations: abscess limb, bacterial infection, blastomycosis, injection site infection, Klebsiella sepsis, pharyngitis streptococcal, pneumonia Klebsiella, sepsis, Staphylococcal bacteremia, Staphylococcal infection, toxoplasmosis. Metabolism and nutrition disorders: dehydration. Musculoskeletal and connective tissue disorders: bone pain aggravated, muscle weakness, neck pain. Neoplasms benign, malignant and unspecified: leukemia cutis. Nervous system disorders: convulsions, intracranial hemorrhage. Psychiatric disorders: confusion. Renal and urinary disorders: hematuria, loin pain, renal failure. Respiratory, thoracic and mediastinal disorders: hemoptysis, lung infiltration, pneumonitis, respiratory distress. Skin and subcutaneous tissue disorders: pyoderma gangrenosum, rash pruritic, skin induration. Surgical and medical procedures: cholecystectomy. Vascular disorders: orthostatic hypotension. OVERDOSAGE One case of overdose with Vidaza was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose. The events resolved without sequelae, and the correct dose was resumed the following day. In the event of overdosage, the patient should be monitored with appropriate blood counts and should receive supportive treatment, as necessary. There is no known specific antidote for Vidaza overdosage. DOSAGE AND ADMINISTRATION First Treatment Cycle The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously, daily for seven days. Patients should be premedicated for nausea and vomiting. Subsequent Treatment Cycles Cycles should be repeated every four weeks. The dose may be increased to 100 mg/m2 if no beneficial effect is seen after two treatment cycles and if no toxicity other than nausea and vomiting has occurred. It is recommended that patients be treated for a minimum of 4 cycles. However, complete or partial response may require more than 4 treatment cycles. Treatment may be continued as long as the patient continues to benefit. Patients should be monitored for hematologic response and renal toxicities (see PRECAUTIONS), and dosage delay or reduction as described below may be necessary. Dosage Adjustment Based on Hematology Laboratory Values: •For patients with baseline (start of treatment) WBC ≥3.0 x109/L, ANC ≥1.5 x109/L, and platelets ≥75.0 x109/L, adjust the dose as follows, based on nadir counts for any given cycle:
Dosage Adjustment Based on Renal Function and Serum Electrolytes: If unexplained reductions in serum bicarbonate levels to less than 20 mEq/L occur, the dosage should be reduced by 50% on the next course. Similarly, if unexplained elevations of BUN or serum creatinine occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment course (see PRECAUTIONS section). Use in Geriatric Patients: Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS section). Preparation of Vidaza Vidaza is a cytotoxic drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing Vidaza suspensions. Please refer to Handling and Disposal section. If reconstituted Vidaza comes into contact with the skin, immediately and thoroughly wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water. Vidaza should be reconstituted aseptically with 4 mL sterile water for injection. The diluent should be injected slowly into the vial. The vial should be inverted 2-3 times and gently rotated until a uniform suspension is achieved. The suspension will be cloudy. The resulting suspension will contain azacitidine 25 mg/mL. Preparation for Immediate Administration: Doses greater than 4 mL should be divided equally into two syringes. The product may be held at room temperature for up to 1 hour, but must be administered within 1 hour after reconstitution. Preparation for Delayed Administration: The reconstituted product may be kept in the vial or drawn into a syringe. Doses greater than 4 mL should be divided equally into two syringes. The product must be refrigerated immediately, and may be held under refrigerated conditions (2°C - 8°C, 36°F- 46°F) for up to 8 hours. After removal from refrigerated conditions, the suspension may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration. Administration To provide a homogeneous suspension, the contents of the syringe must be re-suspended by inverting the syringe 2-3 times and gently rolling the syringe between the palms for 30 seconds immediately prior to administration. Vidaza is administered subcutaneously. Doses greater than 4 mL should be divided equally into 2 syringes and injected into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm). New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, red, or hard. Stability Reconstituted Vidaza may be stored for up to 1 hour at 25°C (77°F) or for up to 8 hours between 2 and 8°C (36 and 46°F). The Vidaza vial is single-use and does not contain any preservatives. Unused portions of each vial should be discarded properly. See Handling and Disposal. Do not save any unused portions for later administration. *FDA于04年5月19日宣布批准Vidaza(商品名：维达扎；通用名：azacitidine<阿扎胞苷>)注射液为治疗骨髓增生异常综合症(Myelodysplastic Syndrome, MDS)的第一个有效药物。 FDA代理专员Lester M. Crawford博士说：“通过恢复骨髓细胞的正常生长和分化，该新药将向有此种罕见的并且在一些病例中恶化为白血病的那些患者提供一个非常需要的治疗手段。FDA将继续给予这类具有显著疗效的产品的批准以最高的优先权。” MDS是由骨髓细胞功能异常、正常血细胞生成减少而引起的一系列疾病的总称。MDS可由治疗其它疾病的药物或放射治疗所致，也可由未知病因引起。MDS的某些类型会恶化为急性髓细胞样白血病(AML)。AML是白细胞增生过度活跃的一种癌症。 FAB（法国-美国-英国）协作组织将MDS分为5型，分别是：顽固性贫血（RA）、环形铁粒幼红细胞性难治性贫血（RARS）、原始细胞过多性难治性贫血（RAEB）、转化型原始细胞过多性难治性贫血（RAEB-T）和慢性粒单核细胞白血病（CMMoL）。 Vidaza属于罕见病治疗药。罕见病治疗药用于治疗患者人数在美国少于20万的罕见疾病或症状。《罕见病药物法》规定：获得所指定罕见病药物上市批准的首个申报者将享有该药物在美国市场上7年期的独占上市权。 据估计，美国每年有7000－12,000的MDS新病例被确诊。这种疾病在各年龄段都可能发生，但是60岁以上人群发病率最高。典型症状包括虚弱、疲劳、感染、易淤伤、出血和发热。MDS患者可能需要接受红血球和血小板的输入，以及针对感染的抗生素治疗。 -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: VIDAZA 100mg/Vial 10Vials/box 原产地英文药品名: AZACITIDINE 原产地英文化合物名称: 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one 中文参考商品译名: 维达扎 100毫克/瓶 10瓶/盒 中文参考药品译名: 阿扎胞苷 中文参考化合物名称: 5-氮杂胞嘧啶核苷 曾用名: 阿扎胞苷、5-氮杂胞苷、5-氮杂胞嘧啶核苷、氮胞苷、氮杂胞苷、Ladakamycin 生产厂家中文参考译名: CELGENE 生产厂家英文名: CELGENE -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: VIDAZA 100mg/Vial 原产地英文药品名: AZACITIDINE 原产地英文化合物名称: 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one 中文参考商品译名: 维达扎 100毫克/瓶 中文参考药品译名: 阿扎胞苷 中文参考化合物名称: 5-氮杂胞嘧啶核苷 曾用名: 阿扎胞苷、5-氮杂胞苷、5-氮杂胞嘧啶核苷、氮胞苷、氮杂胞苷、Ladakamycin 生产厂家中文参考译名: CELGENE 生产厂家英文名: CELGENE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||