英文药名: ZOLADEX Depot(Goserelin Acetate Long Acting Disposable Syringe)

中文药名: 诺雷德（醋酸戈舍瑞林注射剂）

生产厂家: AstraZeneca
药品名称
药品名称：诺雷德 Zoladex
药物别名：戈舍瑞林；goserelin
药物类别：抗肿瘤激素类
诺雷德是一种可在体内逐渐进行生物降解的多聚缓释植入剂。无菌、白色或乳白色柱形，含醋酸戈舍瑞林（相当于3.6毫克和10.8毫克的戈舍瑞林），置于一注射器中，单剂量给药。
生产厂家
AstraZeneca(阿斯利康)
药理作用
药效学：
作用方式：诺雷德(D-Ser (But)6 Azgly10 LHRH) 是促黄体生成素释放激素的一种类似物，长期使用诺雷德抑制脑垂体促黄体生成素的合成，从而引起 男性血清睾丸酮和女性血清雌二醇的下降，停药后这一作用可逆，初期用药时诺雷德同其它LHRH激动剂一样，可暂时增加男性血清睾丸酮和女性血清雌二醇的浓度。在接受诺雷德治疗的早期阶段，一些女性可出现不同程度的阴道出血，持续时间和出血量各有不同。这种现象为雌激素水平下降所导致并可自动停止。
男性病人在第一次注射此药后21天左右血清睾丸酮浓度下降至去势水平，并在以后的治疗中维持此浓度，这可使大多数病人的前列腺肿瘤消退，症状有所改善。
女性患者在初次给药后21天左右血清中雌二醇浓度受到抑制，并在以后每28天的治疗中维持在绝经后水平。这种抑制与激素依赖性的乳腺癌、子宫肌瘤和子宫内膜异位症相关。可导致子宫内膜变薄及多数病人闭经。
诺雷德和铁剂伍用可使贫血的子宫肌瘤患者产生闭经并改善血红蛋白浓度及相关的血液学参数。诺雷德和铁制剂伍用与单独铁剂疗法相比较，前者血红蛋白浓度的增高较后者多1g/dl。在用LHRH类似物治疗期间产生停经且停止治疗后未恢复月经的患者很少见。
药动学：
诺雷德具有几乎完全的生物利用度，每四周用药一次，在无组织蓄积的情况下保持有效的血药浓度，诺雷德与血浆蛋白的结合能力较弱，在肾功能正常情况下血浆清除半衰期为2－4小时，对肾功能不全的病人其半衰期将会增加，此改变在每月一次的治疗中影响很小，故不需要调整剂量，在肝功能不全的病人中其药代动力学无明显变化。
适应症
1.前列腺癌：诺雷德适用于可用激素治疗的前列腺癌。
2.乳腺癌：适用于可用激素治疗的绝经前期及绝经期妇女的乳腺癌。
3.子宫内膜异位症：缓解症状包括减轻疼痛并减少子宫内膜损伤的大小和数目。
4.使子宫内膜变薄：在刮宫术或内膜切除术之前，用诺雷德使子宫内膜 变薄。
5.子宫肌瘤：术前与补铁药伍用可使患有贫血的肌瘤病人的贫血状况得到改善。
用法用量
成人：
-- 在腹部皮下注射诺雷德一支，每28天一次。
-- 肾功能不全者不需调整剂量。
-- 肝功能不全者不需调整剂量。
-- 老年病人不需调整剂量。
-- 子宫内膜异位症的治疗不应超过六个月，因为目前尚没有长期治疗的临床数据，考虑到有关骨质丢失的问题，应避免重复疗程。
-- 用于使子宫内膜变薄：每隔四周注射一支诺雷德共注射两次。手术在第二次注射后两周内进行。
-- 对由于子宫肌瘤导致贫血的妇女，手术前三月之内给予诺雷德及补铁治疗。
儿童：
-- 诺雷德不推荐用于儿童。
任何疑问，请遵医嘱！
禁忌症
已知对诺雷德或LHRH类似物过敏的病人不可使用诺雷德。
妊娠期及哺乳期妇女不可使用诺雷德。
注意事项
由于诺雷德的安全性及有效性在儿童中尚未论证，故儿童病人不推荐使用诺雷德。
男性：
对有发展为尿道阻塞或脊髓压迫危险的男性病人 诺雷德应慎用，而且在 治疗的第一个月期间应密切监护病人，如果因尿道梗阻而引起脊髓压迫或肾脏损伤并恶化，则应给予适当治疗。
女性：
妇女使用LHRH激动剂可能引起骨密度丢失，从目前所得到的诺雷德研究数据表明六个月疗程结束时椎骨矿物质密度平均下降4.6％，再经六个月后逐渐恢复到只比基值低2.6％。
对已知有骨代谢异常的妇女使用, 诺雷德时应注意。 诺雷德可引起子宫颈阻抗增加，因而可导致扩宫困难。
目前尚无用诺雷德治疗子宫内膜异位症超过六个月的临床数据。
妊娠和哺乳
虽然动物生殖毒理研究没有提供致畸的证据，但如果在妊娠期间使用LHRH激动剂理论上有流产或致畸的危险性，因而在妊娠期间不要使用。对于可能妊娠的妇女在使用本药前应先仔细检验以排除妊娠可能，在治疗中应使用非激素的避孕方法，直到治疗后月经恢复为止。
哺乳期间不推荐使用诺雷德。
对驾驶和机械操作者的影响
无证据表明诺雷德对上述能力有损害。
不良反应
一般的：
过敏反应发生率很低，一些过敏现象已见报道。关节痛已见报道。有报道出现皮疹，多为轻度，不需中断治疗即可恢复。
血压的变化，服用诺雷德的病人，发生低血压或高血压反应的病例已偶见报道。这种变化通常很短暂，继续治疗或停止治疗后均可恢复，很少需要停药及其它药物治疗。偶然出现的局部反应包括在注射位置上有轻度瘀血。
男性：
男性病人副作用包括潮红和性欲下降，少有必需中断治疗，偶见乳房肿胀和触痛，给药初期前列腺癌症病人可能有骨骼疼痛暂时性加重，应对症处理。尿道梗阻和脊髓压缩的个别病例也曾有报道。
女性：
女性病人副作用有潮红，多汗及性欲下降，无需中止治疗；也曾观察到头痛，情绪变化如抑郁，阴道干燥及乳房大小的变化。治疗初期乳腺癌的病人会有症状的加剧，应按症状进行处理。子宫肌瘤患者可见肌瘤退行性变性。在治疗初期，有骨转移的乳腺癌患者很少发展为高钙血征。
药物过量
人体尚无超剂量用药的试验。动物试验表明使用超剂量的诺雷德时除对性激素浓度和生殖道的预想的作用外无其它影响，如发生超量使用的情况，应对症处理。
与处方有关的临床前安全资料
长期重复注射诺雷德之后曾在雄性鼠中观察到良性脑垂体肿瘤发病率上升的现象，这一发现与对雄鼠阉割后所得结果相似，尚未发现与人体使用的经验有任何关联。 在小鼠体内，长期重复使用几倍人用的剂量下在消化道内产生了组织结构的变化，这可由胃部幽门区域良性增生和胰岛细胞增殖来证明。这些事实与临床的关系尚不清楚。
规格
Zoladex (goserelin acetate)
Zoladex: 3.6mg in a biodegradable depot; single-dose syringe applicator.
Zoladex LA: 10.8mg in a biodegradable depot; single-dose syringe applicator.

Zoladex 3.6 mg (Canada)Zoladex LA (Canada)
Pharmacology
Synthetic analog of gonadotropin-releasing hormone (GnRH) that acts as potent inhibitor of pituitary gonadotropin secretion.
Pharmacokinetics
Absorption
T max for the 3.6 mg implant is 12 to 15 days in men and 8 to 22 days in women. T max for the 10.8 mg implant is 2 h in men. C max for the 3.6 mg implant is about 1.46 ng/mL in women and 2.84 ng/mL in men and for the 10.8 mg is about 8 ng/mL in men.
Distribution
Vd is 44.1 L in men and 20.3 L in women. Protein binding is 27%.
Metabolism
Hydrolysis of the C-terminal amino acids.
Elimination
The t 1/ 2 for the 3.6 mg implant is 4.2 h in men and 2.3 h in women. More than 90% is excreted in urine, 20% unchanged. Mean systemic Cl for the 3.6 mg implant is 111 mL/min in men and to 164 mL/min in women.
Onset
1 wk.
Peak
2 to 4 wk.
Special Populations
Renal Function Impairment
In CrCl less than 20 mL/min, the t 1/ 2 is 12.1 h.
Increased body weight
A decline in AUC of about 1% to 2.5% was observed with a kg increase in body weight.
Indications and Usage
Goserelin 3.6 mg implant
Palliative treatment of advanced breast cancer in pre- and peri-menopausal women; treatment of endometriosis; as an endometrial thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.
Goserelin 3.6 and 10.8 mg implants
Palliative treatment of advanced carcinoma of the prostate; in combination with flutamide for management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate.
Contraindications
Breast-feeding; women being treated for endometriosis or endometrial thinning who are or may become pregnant; known hypersensitivity to LHRH, LHRH agonist analogs, or any component of the product; 10.8 mg goserelin implant is not indicated in women.
Dosage and Administration
Adults 28 days
Subcutaneous 3.6 mg implant every 28 days into upper abdominal wall by sterile technique under health care provider's supervision.
Adults 12 weeks
Subcutaneous 10.8 mg implant every 12 wk into upper abdominal wall by sterile technique under health care provider's supervision.
Advanced Breast CancerAdults
Subcutaneous (3.6 mg only). Intended for long-term administration unless clinically inappropriate.
EndometriosisAdults
Subcutaneous (3.6 mg only). Current recommended duration of treatment is 6 mo.
Endometrial ThinningAdults
Subcutaneous (3.6 mg only). Recommendation is 1 or 2 depots, given 4 wk apart. When 1 depot is administered, surgery should be at 4 wk. When 2 depots are administered, surgery should be within 2 to 4 wk following the second depot.
Prostatic CarcinomaAdults
Subcutaneous (3.6 or 10.8 mg). Intended for long-term administration unless clinically inappropriate.
Stage B2 to C Prostatic CarcinomaAdults
Subcutaneous (3.6 or 10.8 mg only). When given in combination with radiotherapy and flutamide, start treatment 8 wk prior to initiating radiotherapy and continue during radiation therapy. A regimen using goserelin 3.6 mg depot 8 wk before radiotherapy, followed in 28 days by the 10.8 mg depot, can be administered. Alternatively, 4 injections of 3.6 mg depot can be administered at 28 day intervals, 2 depots preceding the 2 during radiotherapy.
General Advice
Dose (number or strength of implants), frequency of implantation, and duration of therapy are variable depending on condition being treated and clinical response.
For subcutaneous implantation only. Not for intradermal, IM, or oral administration.
Using preloaded syringe with attached needle, pellets are injected into the anterior abdominal wall below the navel line.
Follow manufacturer's instructions regarding preparation of injection site, preparation of preloaded syringe, injection of implant, and disposal of used syringe.
If blood appears in syringe, do not inject implant. Instead, withdraw needle and discard syringe. Use new syringe and inject implant at a different site.
Pellets can be localized by ultrasound if surgical removal is necessary.
Storage/Stability
Store preloaded syringe in foil pouch at controlled room temperature (less than 77°F). Do not remove syringe from foil pouch until just prior to use.
Drug Interactions
None well documented.
Laboratory Test Interactions
Diagnostic tests of pituitary-gonadotropic and gonadal functions
Results may be misleading.
Estrogen
Drug may cause initial transient increase in serum levels in women.
Hypercalcemia in patients with bone metastases
Drug may cause initial transient increase.
Testosterone
Drug may cause initial transient increases in serum levels in men.
Adverse Reactions
Cardiovascular
Women
Vasodilation (57%); migraine (7%); hypertension (6%); chest pain, hemorrhage, palpitations, tachycardia (at least 1%)
Men
CHF (5%); angina pectoris, arrhythmia, cerebral ischemia, cerebrovascular accident, chest pain, heart failure, hypertension, MI, peripheral vascular disorder, pulmonary embolus, varicose veins (greater than 1% but less than 5%).
CNS
Women
Headache (75%); emotional lability (60%); depression (54%); insomnia, asthenia (11%); dizziness (6%); fatigue, lethargy, malaise, nervousness (5%); hypertonia, abnormal thinking, anxiety, paresthesia somnolence (at least 1%).
Men
Lethargy (8%); dizziness, insomnia (5%); anxiety, depression, headache, paresthesia (greater than 1% but less than 5%).
Dermatologic
Women
Hot flashes (96%); sweating (45%); acne (42%); seborrhea (26%); hirsutism (7%); hair disorder (4%); pruritus (2%); alopecia, dry skin, ecchymosis, skin discoloration (at least 1%).
Men
Hot flashes (62%); rash, sweating (6%); herpes simplex, pruritus (greater than 1% but less than 5%).
EENT
Women
Pharyngitis (6%); amblyopia, dry eyes (at least 1%).
GI
Women
Nausea, abdominal pain (11%); vomiting (4%); increased appetite (2%); anorexia, constipation, diarrhea, dry mouth, dyspepsia, flatulence (at least 1%).
Men
Anorexia, nausea (5%); abdominal pain, constipation, diarrhea, hematemesis, ulcer, vomiting (greater than 1% but less than 5%).
Genitourinary
Women
Vaginitis (75%); decreased libido (61%); breast atrophy (33%); breast enlargement, pelvic symptoms (18%); dyspareunia (14%); increased libido (12%); breast pain, dysmenorrhea (7%); uterine hemorrhage (6%); vulvovaginitis (5%); menorrhagia (4%); urinary frequency, UTI, vaginal hemorrhage (at least 1%).
Men
Sexual dysfunction (21%); decreased erections (18%); lower UTIs (13%); bladder neoplasm, breast swelling and tenderness, hematuria, impotence, renal function impairment, urinary obstruction, urinary frequency, urinary incontinence, urinary infrequency, urinary retention, urinary tract disorder, UTI (greater than 1% but less than 5%).
Hematologic-Lymphatic
Men
Anemia (greater than 1% but less than 5%).
Hypersensitivity
Anaphylaxis.
Local
Women
Elevated liver enzymes (ALT, AST) (at least 1%).
Metabolic-Nutritional
Women
Weight gain (3%).
Men
Diabetes mellitus, gout, hyperglycemia, weight increase (greater than 1% but less than 5%); decreased bone mineral density and bony fracture in men, osteoporosis (postmarketing).
Musculoskeletal
Women
Back pain (7%); myalgia (3%); leg cramps (2%); arthralgia, joint disorder (at least 1%).
Men
Back pain (greater than 1% but less than 5%).
Respiratory
Women
Sinusitis (3%); bronchitis, epistaxis, increased cough, rhinitis (at least 1%).
Men
Upper respiratory infection (7%); chronic obstructive pulmonary disease (5%); dyspnea, increased cough, pneumonia (greater than 1% but less than 5%).
Miscellaneous
Women
Tumor flare (23%); peripheral edema (21%); pain (17%); infection (13%); flu syndrome (5%); voice alterations (3%), edema, fever (at least 1%).
Men
Pain, edema (8%); flu syndrome, sepsis, peripheral edema (greater than 1% but less than 5%).
Precautions
Monitor
Testosterone/Prostatic acid phosphatase
Ensure serum testosterone and prostatic acid phosphatase are periodically measured in patient being treated for prostate cancer to assess therapeutic response.
Pregnancy
Category D (breast cancer); Category X (endometriosis, endometrial thinning, 10.8 mg strength).
Lactation
Undetermined. Discontinue the drug prior to breast-feeding.
Children
Safety and efficacy not established.
Hypersensitivity
Antibody formation to goserelin has been observed. Anaphylactic reactions are possible.
Special Risk Patients
Isolated cases of spinal cord compression and ureteral obstruction have been reported in men. Use with caution in patients prone to these problems.
Bone mineral density changes
Decreases in vertebral trabecular bone mineral density have been observed; patients with certain risk factors (eg, alcohol or tobacco abuse, family history of osteoporosis) may be at additional risk.
Breast cancer worsening
Drug initially causes transient increase in estrogen. Worsening of signs and symptoms of breast cancer, such as bone pain, may occur during the first few weeks of treatment.
Prostatic cancer worsening
Drug initially causes transient increase in testosterone. Worsening of signs and symptoms of prostate cancer, such as bone pain, may occur during first few weeks of treatment.
10.8 mg implant
The 10.8 mg implant is not indicated in women as the data are insufficient to support reliable suppression of serum estradiol.
Hormone replacement therapy (HRT)
Clinical studies suggest the addition of HRT (estrogens or progestins) to goserelin may decrease the occurrence of vasomotor symptoms and vaginal dryness associated with hypoestrogenism without compromising the efficacy of goserelin in relieving pelvic symptoms. The optimal drugs, dose, and duration of treatment not established.
Hypercalcemia
Hypercalcemia has occurred in some prostate and breast cancer patients with bone metastases after starting goserelin treatment. Ensure serum calcium levels are monitored in patient being treated for prostate or breast cancer. Inform health care provider immediately if hypercalcemia is noted or patient develops signs or symptoms of hypercalcemia (eg, polyuria, confusion, drowsiness). Be prepared to treat appropriately (eg, sodium chloride 0.9% injection, furosemide).
Hypoestrogenism
Hypoestrogenism may be induced by goserelin, which results in loss of bone mineral density over the course of treatment and may be irreversible. Adverse reactions occurring with hypoestrogenism most frequently include hot flashes, headaches, vaginal dryness, emotional lability, changes in libido, depression, sweating, and change in breast size.
Pituitary gonadal axis
As with other hormonal interventions that disrupt pituitary-gonadal axis, some patients may experience a delay in return to menses and, rarely, patients may experience persistent amenorrhea.
Vaginal bleeding
Some women experience vaginal bleeding of variable duration and intensity. The bleeding represents estrogen withdrawal bleeding and is expected to stop spontaneously.
Patient Information
Advise patient, family, or caregiver that medication will be prepared and administered by health care professionals in a health care setting.
Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
Advise patient that pellet is biodegradable and will be absorbed by the body and does not have to be removed when next dose is due or when therapy is discontinued.
Caution patient that missing 1 or more doses of goserelin may result in loss of beneficial effects and to be sure to return as scheduled for additional doses of medication.
Advise patient being treated for prostate or breast cancer that temporary worsening of symptoms or additional signs and symptoms of the cancer may develop during the first few weeks of therapy but should improve once the medication begins to take effect.
Advise women that the most common adverse reaction of therapy are associated with estrogen deficiency (eg, change in breast size, reduction or loss of libido, depression, emotional lability, hot flashes or flushes, sweating, vaginal dryness). Advise patient to be prepared to discuss potential value of starting hormone replacement therapy with health care provider if estrogen deficiency symptoms occur and are intolerable.
Advise patient, family, or caregiver to immediately report any of the following to health care provider: frequent urination or little or no urination; unexplained drowsiness; lower stomach or pelvic-area pain; abnormal skin sensations; numbness or tingling sensations; loss of sphincter control; unexplained weakness; rash or hives; difficulty breathing or unexplained shortness of breath; pain, redness, or swelling at injection site.
Advise women that menstruation should stop as a result of therapy with goserelin and to notify health care provider if regular menstruation continues. Caution patient that breakthrough menstrual bleeding and/or ovulation may occur if 1 or more does of goserelin are missed.
Instruct women of childbearing potential to use effective nonhormonal contraception during treatment and until the return of menses or for at least 12 wk following the last pellet implantation.

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产地国家: 美国
原产地英文商品名:
ZOLADEX Depot 3.6mg/Implant
原产地英文药品名:
GOSERELIN ACETATE
中文参考商品译名:
诺雷德 3.6毫克/注入剂
中文参考药品译名:
醋酸戈舍瑞林
生产厂家中文参考译名:
阿斯利康
生产厂家英文名:
AstraZeneca