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英文药名: Lupron Depot(Leuprolide Acetate Prefilled Syringes) 中文药名: 醋酸亮丙瑞林预充注射剂 品牌药生产厂家: Abbott 规格 3.75mg; 7.5mg; 11.25mg; 22.5mg; 30mg 药品名称 通用名：注射用醋酸亮丙瑞林 药理毒理 子宫内膜异位症; 伴有月经过多、下腹痛、腰痛及贫血等的子宫肌瘤；绝经前乳腺癌，且雌激素受体阳性患者；前列腺癌；中枢性性早熟症。 子宫内膜异位症：通常，成人每4周1次，皮下注射醋酸亮丙瑞林3.75mg。当患者体重低于50kg时，可以使用1.88mg的制剂。初次给药应从月经周期的1～5日开始。 内分泌系统：发热，颜面潮红，发汗，性欲减退，阳痿，男子女性化乳房，睾丸萎缩，会阴不适等现象。 对本制剂成分、合成的LH-RH或LH-RH衍生物有过敏史者。孕妇或有可能怀孕的妇女，或哺乳期妇女；有性质不明的、异常的阴道出血者[有可能为恶性疾病]。 首次用药初期，由于高活性LH－RH衍生物对垂体－性腺系统的刺激作用，使血清睾丸素浓度上升，可见骨性疼痛暂时加重，尿储留或脊髓压迫症状，应对症处理。已存在由脊髓压迫或尿储留引起的肾功能障碍者或者是有重新发作可能性的患者及高龄者慎用。治疗时一定要确认患者未妊娠，且于月经周期的1-5天开始给药，在治疗期内应采用非激素性方法避孕。 孕妇以及可能怀孕的妇女或哺乳妇女不应给予醋酸亮丙瑞林。[已有LH-RH衍生物导致流产的报告。在本品的动物研究中，观察到胎鼠和胎兔死亡率增加和体重减轻，而且胎兔骨骼形成异常有增加的趋势。在大鼠中还观察到醋酸亮丙瑞林可进入母鼠乳转运。] 醋酸亮丙瑞林对早产儿，新生儿和乳儿的安全性尚未确定。 产品规格： 注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
LUPRON DEPOT is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, becomes a suspension intended as a monthly intramuscular injection. The front chamber of LUPRON DEPOT 7.5 mg prefilled dual-chamber syringe contains leuprolide acetate (7.5 mg), purified gelatin (1.3 mg), DL-lactic and glycolic acids copolymer (66.2 mg), and D-mannitol (13.2 mg). The second chamber of diluent contains carboxymethylcellulose sodium (5 mg), D-mannitol (50 mg), polysorbate 80 (1 mg), water for injection, USP, and glacial acetic acid, USP to control pH. During the manufacture of LUPRON DEPOT 7.5 mg, acetic acid is lost, leaving the peptide. CLINICAL PHARMACOLOGY Leuprolide acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses. Animal and human studies indicate that following an initial stimulation, chronic administration of leuprolide acetate results in suppression of ovarian and testicular steroidogenesis. This effect is reversible upon discontinuation of drug therapy. Administration of leuprolide acetate has resulted in inhibition of the growth of certain hormone dependent tumors (prostatic tumors in Noble and Dunning male rats and DMBA-induced mammary tumors in female rats) as well as atrophy of the reproductive organs. In humans, administration of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of leuprolide acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to castrate levels. In premenopausal females, estrogens are reduced to postmenopausal levels. These decreases occur within two to four weeks after initiation of treatment. Castrate levels of testosterone in prostatic cancer patients have been demonstrated for up to 10 years. Leuprolide acetate is not active when given orally. Pharmacokinetics Absorption Following a single injection of LUPRON DEPOT 7.5 mg to patients, mean plasma leuprolide concentration was almost 20 ng/mL at 4 hours and 0.36 ng/mL at 4 weeks. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. Nondetectable leuprolide plasma concentrations have been observed during chronic LUPRON DEPOT 7.5 mg administration, but testosterone levels appear to be maintained at castrate levels. Distribution The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%. Metabolism In healthy male volunteers, a 1 mg bolus of leuprolide administered intravenously revealed that the mean systemic clearance was 7.6 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model. In rats and dogs, administration of 14C-labeled leuprolide was shown to be metabolized to smaller inactive peptides, a pentapeptide (Metabolite I), tripeptides (Metabolites II and III) and a dipeptide (Metabolite IV). These fragments may be further catabolized. The major metabolite (M-I) plasma concentrations measured in 5 prostate cancer patients reached maximum concentration 2 to 6 hours after dosing and were approximately 6% of the peak parent drug concentration. One week after dosing, mean plasma M-I concentrations were approximately 20% of mean leuprolide concentrations. Excretion Following administration of LUPRON DEPOT 3.75 mg to 3 patients, less than 5% of the dose was recovered as parent and M-I metabolite in the urine. Special Populations The pharmacokinetics of the drug in hepatically and renally impaired patients have not been determined. Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT. However, because leuprolide acetate is a peptide that is primarily degraded by peptidase and the drug is only about 46% bound to plasma proteins, drug interactions would not be expected to occur. CLINICAL STUDIES In an open-label, non-comparative, multicenter clinical study of LUPRON DEPOT 7.5 mg, 56 patients with stage D2 prostatic adenocarcinoma and no prior systemic treatment were enrolled. The objectives were to determine if a 7.5 mg depot formulation of leuprolide injected once every 4 weeks would reduce and maintain serum testosterone to castrate range (≤;50 ng/dL), to evaluate objective clinical response, and to assess the safety of the formulation. During the initial 24 weeks, serum testosterone was measured weekly, biweekly, or every four weeks and objective tumor response assessments were performed at Weeks 12 and 24. Once the patient completed the initial 24-week treatment phase, treatment continued at the investigator's discretion. Data from the initial 24-week treatment phase are summarized in this section. In the majority of patients, serum testosterone increased by 50% or more above baseline during the first week of treatment. Serum testosterone suppressed to the castrate range within 30 days of the initial depot injection in 94% (51/54) of patients for whom testosterone suppression was achieved (2 patients withdrew prior to onset of suppression) and within 66 days in all 54 patients. Mean serum testosterone suppressed to castrate level by Week 3. The median dosing interval between injections was 28 days. One escape from suppression (2 consecutive testosterone values greater than 50 ng/dL after achieving castrate level) was noted at Week 18, associated with a substantial dosing delay. In this patient, serum testosterone returned to the castrate range at the next monthly measurement. Serum testosterone was minimally above the castrate range on a single occasion for 4 other patients. No clinical significance was attributed to these rises in testosterone. Secondary efficacy endpoints evaluated included objective tumor response, assessed by clinical evaluations of tumor burden (complete response, partial response, objectively stable, and progression), as well as changes in local disease status, assessed by digital rectal examination, and changes in prostatic acid phosphatase (PAP). These evaluations were performed at Weeks 12 and 24. The objective tumor response analysis showed a "no progression" (ie. complete or partial response, or stable disease) in 77% (40/52) of patients at Week 12, and in 84% (42/50) of patients at Week 24. Local disease improved or remained stable in all (42) patients evaluated at Week 12 and in 98% (41/42) of patients elevated at Week 24. PAP normalized or decreased at Week 12 and/or 24 in the majority of patients with elevated baseline PAP. Periodic monitoring of serum testosterone and PSA levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions. INDICATIONS AND USAGE LUPRON DEPOT 7.5 mg is indicated in the palliative treatment of advanced prostatic cancer. CONTRAINDICATIONS
WARNINGS Initially, LUPRON DEPOT, like other LH-RH agonists, causes increases in serum levels of testosterone to approximately 50% above baseline during the first week of treatment. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may occasionally develop during the first few weeks of LUPRON DEPOT treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other LH-RH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. For patients at risk, initiation of therapy with daily LUPRON® (leuprolide acetate) Injection (see DOSAGE AND ADMINISTRATION section in the LUPRON Injection labeling) for the first two weeks to facilitate withdrawal of treatment may be considered. If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted. PRECAUTIONS Information for Patients An information pamphlet for patients is included with the product. General Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy (see WARNINGS section). Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes. Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice. Laboratory Tests Response to LUPRON DEPOT 7.5 mg should be monitored by measuring serum levels of testosterone as well as prostate-specific antigen. In the majority of patients, testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week. Castrate levels were reached within two to four weeks and once achieved were maintained for the duration of treatment in all 54 patients. Minimal and transient increases to above the castrate level occurred in eight patients (see CLINICAL STUDIES section). Drug Interactions (See Pharmacokinetics.) Drug/Laboratory Test Interactions Administration of LUPRON DEPOT in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within three months after treatment is discontinued. Due to the suppression of the pituitary-gonadal system by LUPRON DEPOT, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and for up to three months after discontinuation of LUPRON DEPOT may be affected. Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies were conducted in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no leuprolide acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities. Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of a mutagenic potential. Clinical and pharmacologic studies in adults (≥ 18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks. Pregnancy Category X See CONTRAINDICATIONS section. Pediatric Use See LUPRON DEPOT-PED® (leuprolide acetate for depot suspension) labeling for the safety and effectiveness of the monthly formulation in children with central precocious puberty. Geriatric Use In the clinical trials for LUPRON DEPOT, the majority (68%) of the subjects studied were at least 65 years of age. Therefore, the labeling reflects the pharmacokinetics, efficacy and safety of LUPRON DEPOT in this population. Adverse Reactions Clinical Trials In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. Potential exacerbations of signs and symptoms during the first few weeks of treatment is a concern in patients with vertebral metastases and/or urinary obstruction or hematuria which, if aggravated, may lead to neurological problems such as temporary weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms (see WARNINGS section). In a clinical trial of LUPRON DEPOT 7.5 mg, the following adverse reactions were reported in 5% or more of the patients during the initial 24-week treatment period regardless of causality.
In this same study, the following adverse reactions were reported in less than 5% of the patients on LUPRON DEPOT 7.5 mg. Body as a Whole - Asthenia, Cellulitis, Fever, Headache, Injection site reaction, Neoplasm; Cardiovascular System - Angina, Congestive heart failure; Digestive System - Anorexia, Dysphagia, Eructation, Peptic ulcer; Hemic and Lymphatic System - Ecchymosis; Musculoskeletal System - Myalgia; Nervous System - Agitation, Insomnia/sleep disorders, Neuromuscular disorders; Respiratory System - Emphysema, Hemoptysis, Lung edema, Sputum increased; Skin and Appendages - Hair disorder, Skin reaction; Urogenital System - Balanitis, Breast enlargement, Urinary tract infection. Laboratory: Abnormalities of certain parameters were observed, but their relationship to drug treatment are difficult to assess in this population. The following were recorded in ≥5% of patients at final visit: Decreased albumin, decreased hemoglobin/hematocrit, decreased prostatic acid phosphatase, decreased total protein, decreased urine specific gravity, hyperglycemia, hyperuricemia, increased BUN, increased creatinine, increased liver function tests (AST, LDH), increased phosphorus, increased platelets, increased prostatic acid phosphatase, increased total cholesterol, increased urine specific gravity, leukopenia. Postmarketing During postmarketing surveillance, which includes other dosage forms and other patient populations, the following adverse events were reported. Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported. Rash, urticaria, and photosensitivity reactions have also been reported. Localized reactions including induration and abscess have been reported at the site of injection. Symptoms consistent with fibromyalgia (eg, joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported individually and collectively. Cardiovascular System - Hypotension, Myocardial infarction, Pulmonary embolism; Hemic and Lymphatic System - Decreased WBC; Central/Peripheral Nervous System - Convulsion, Peripheral neuropathy, Spinal fracture/paralysis; Endocrine System – Diabetes; Musculoskeletal System - Tenosynovitis-like symptoms; Urogenital System - Prostate pain. Changes in Bone Density: Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LH-RH agonist analog. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprolide acetate for at least six months, underwent bone density studies as a result of pain. The leuprolide-treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density. Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. See other LUPRON DEPOT and LUPRON Injection package inserts for other events reported in women and pediatric populations. OVERDOSAGE In clinical trials using daily subcutaneous leuprolide acetate in patients with prostate cancer, doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose. DOSAGE AND ADMINISTRATION LUPRON DEPOT Must Be Administered Under The Supervision Of A Physician. The recommended dose of LUPRON DEPOT is 7.5 mg, incorporated in a depot formulation. The lyophilized microspheres are to be reconstituted and administered monthly as a single intramuscular injection.
Since the product does not contain a preservative, the suspension should be discarded if not used immediately. As with other drugs administered by injection, the injection site should be varied periodically. HOW SUPPLIED Each LUPRON DEPOT 7.5 mg kit (NDC 0074-3642-03) contains:
The prefilled dual-chamber syringe contains sterile lyophilized microspheres of leuprolide acetate incorporated in a biodegradable lactic acid/glycolic acid copolymer. When mixed with 1 mL of accompanying diluent, LUPRON DEPOT 7.5 mg is administered as a single monthly intramuscular injection. Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [See USP Controlled Room Temperature] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Lupron Depot（醋酸亮丙瑞林预充注射剂）简介：
英文药名: Lupron Depot(Leuprolide Acetate Prefilled Syringes)
中文药名: 醋酸亮丙瑞林预充注射剂
品牌药生产厂家: Abbott
规格
3.75mg; 7.5mg; 11.25mg; 22.5mg; 30mg
药品名称
通用名：注 ... 责任编辑：admin |
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