近日，Endo制药公司得到 FDA批准Aveed(十一烷酸睾酮[testosterone undecanoate])注射剂为成年男性有性腺机能减退或“低-睾酮” 伴随睾酮[testosterone]不足或缺乏。
Aveed适用于产生在正常范围血清睾酮水平通过一个在治疗开始肌内注射给予一次单次3 mL(750 mg)，在第4周再1次，然后以后每10周。
Aveed还对低睾酮男性扩展治疗选择。到现在为止，这些选择包括持续更短时间的注射剂，局部外用凝胶，和皮肤贴剂组成。
批准日期: 2014年3月5日；公司: Endo Pharmaceuticals
AVEED(十一烷酸睾酮[testosterone undecanoate])注射剂，为肌肉注射使用CIII
美国初次批准：1953
作用机制
内源性雄激素，包括睾酮和二氢睾酮(DHT)是负责男性器官正常生长和发育和为维持第二性征特征。这些作用包括前列腺，精囊腺，阴茎和阴囊的生长和成熟；男性毛发分布发育，例如面，耻骨，胸，和腋毛；喉扩大，声带变厚，和身体身体的肌肉和脂肪分布的变化。 男性性腺机能减退，来自睾酮分泌不足结果的一种临床综合征，有两种主要病因。原发性性腺机能减退是生殖腺缺陷引起，例如Klinefelter氏综合征或Leydig细胞增生不良，而继发性性腺机能减退是下视丘(或垂体)产生充分促性腺激素(FSH，LH)的衰竭所致。
适应证和用途
Aveed(十一烷酸睾酮)注射剂是一种雄激素适用在伴随内源性睾酮不足或缺乏成年男性为睾酮替代治疗：
（1）原发性性腺机能减退(先天性或获得性)
（2）低性腺促素性腺机能减退(先天性或获得性)
Aveed只应在需要睾酮替代治疗和产品获益胜过肺油微栓塞和过敏反应的严重风险患者中使用。
使用限制：
Aveed在小于18岁男性的安全性和疗效没有保留。慎用，尤其被确定有心，肾患者.
剂量和给药方法
（1）只为进入注射使用.
（2）在初始时，在4周时，和其后每10周肌肉注射3 mL(750 mg)
（3）每次注射Aveed后，在严重POME反应或过敏反应事件中为了提供适当医学处理在卫生保健情况观察患者30分钟。
（4）遵循油溶液肌肉给药通常注意事项深度注射Aveed入臀部肌肉。
剂型和规格
无菌可注射卷边密封和灰色塑料帽750mg/3mL(250 mg/mL)十一烷酸睾酮。
禁忌证
（1）有乳癌或已知或怀疑前列腺癌男性。
（2）妊娠或哺乳妇女。睾酮可能致胎儿危害。
（3）对Aveed或其成分(睾酮十一酸酯，精制蓖麻油，苯甲酸苄酯)已知超敏性。
警告和注意事项
（1）监视患者有良性前列腺肥大(BPH)对BPH体征和症状恶化。
（2）外源性给予雄激素可能导致无精子。
（3）在有预先存在心，肾，或肝病患者水肿有或无充血性心衰可能是并发症。
（4）在那些有风险因子可能发生睡眠呼吸暂停。
（5）定期地监视前列腺特异性抗原(PSA)，血红蛋白，红细胞比容，和脂质浓度。
不良反应
最常报道不良反应(≥2%)是痤疮，注射部位疼痛，前列腺特异性抗原(PSA)增加，雌二醇增加，性腺机能减退，疲劳，易怒，血红蛋白增加，失眠，和情绪波动。
药物相互作用
（1）在糖尿病患者中雄激素可能减低血糖，和因此可能减低胰岛素需求。
（2）用雄激素可能见到抗凝活性变化。用华法林[warfarin]患者中建议更频繁监视国际标准化比值(INR)和凝血酶原时间。
（3）睾酮与皮质激素类的使用可能导致液体或肝病增加。
特殊人群中使用
老年患者：没有足够长期安全性数据评估心血管病和前列腺癌的潜在风险。
包装供应/贮存和处置
Aveed，NDC 67979-511-43：750 mg/3 mL (250 mg/mL)十一烷酸睾酮无菌可注射溶液在一个琥珀色玻璃小瓶与银色卷边密封和灰色塑料帽内提供。每个小瓶独立包装在一纸盒内。
贮存在控制室温25 ºC(77 ºF)；外出允许至15 -30 ºC(59 -86 ºF)[见USP控制室温]在其原始纸盒直至指示日期。
使用前，应肉眼观测小瓶。只应使用无颗粒小瓶。单次使用小瓶。遗弃未使用部分。
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f80f025b-17d8-40af-8739-20ce07902045 。

INDICATIONS AND USAGE
AVEED® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.
Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range.
AVEED® should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis.
Limitations of use:
Safety and efficacy of AVEED® in males less than 18 years old have not been established.
IMPORTANT SAFETY INFORMATION
WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS
Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose.
Following each injection of AVEED®, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis.
Because of the risks of serious POME reactions and anaphylaxis, AVEED® is available only through a restricted program under a Risk eva luation and Mitigation Strategy (REMS) called the AVEED® REMS Program.
CONTRAINDICATIONS
Men with carcinoma of the breast or known or suspected carcinoma of the prostate.
Women who are or may become pregnant, or who are breastfeeding. Testosterone can cause fetal harm when administered to a pregnant woman. AVEED® may cause serious adverse reactions in nursing infants. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization.
Men with known hypersensitivity to AVEED® or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate).
WARNINGS AND PRECAUTIONS
Serious Pulmonary Oil Microembolism (POME) Reactions and Anaphylaxis
Serious POME reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL). The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization. To minimize the risk of intravascular injection of AVEED®, care should be taken to inject the preparation deeply into the gluteal muscle, being sure to follow the recommended procedure for intramuscular administration.
In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate.
Both serious POME reactions and anaphylaxis can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. Patients with suspected hypersensitivity reactions to AVEED® should not be re-treated with AVEED®.
Following each injection of AVEED®, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions and anaphylaxis.
AVEED® Risk eva luation and Mitigation Strategy (REMS) Program
AVEED® is available only through a restricted program called the AVEED® REMS Program because of the risk of serious POME and anaphylaxis.
Notable requirements of the AVEED® REMS Program include the following:
Healthcare providers who prescribe AVEED® must be certified with the REMS Program before ordering or dispensing AVEED®.
Healthcare settings must be certified with the REMS Program and have healthcare providers who are certified before ordering or dispensing AVEED®. Healthcare settings must have on-site access to equipment and personnel trained to manage serious POME and anaphylaxis.
Further information is available at www.AveedREMS.com or call 1-855-755-0494.
Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer - Patients with BPH treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at an increased risk for prostate cancer. eva luate patients for prostate cancer prior to initiating and during treatment with androgens.
Polycythemia - Increases in hematocrit, reflective of increases in red blood cell mass, may require discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-eva luate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events.
Venous thromboembolism (VTE) - There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as AVEED®. eva luate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with AVEED® and initiate appropriate workup and management.
Use in Women - Due to lack of controlled eva luations in women and potential virilizing effects, AVEED® is not indicated for use in women.
Potential for Adverse Effects on Spermatogenesis - With large doses of exogenous androgens, including AVEED®, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.
Hepatic Adverse Effects - Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. AVEED® is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue AVEED® while the cause is eva luated.
Edema - Androgens, including AVEED®, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
Gynecomastia - Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism.
Sleep Apnea - The treatment of hypogonadal men with testosterone products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.
Lipids - Changes in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy.
Hypercalcemia - Androgens, including AVEED®, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.
Decreased Thyroxine-binding Globulin - Androgens, including AVEED®, may decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Laboratory Monitoring - Monitor prostatic specific antigen (PSA), hemoglobin, hematocrit, and lipid concentrations at the start of treatment and periodically thereafter.
ADVERSE REACTIONS
AVEED® was eva luated in an 84-week clinical study using a dose regimen of 750 mg (3 mL) at initiation, at 4 weeks, and every 10 weeks thereafter in 153 hypogonadal men. The most commonly reported adverse reactions (≥2%) were: acne, injection site pain, prostate specific antigen increased, hypogonadism, estradiol increased, fatigue, irritability, hemoglobin increased, insomnia, and mood swings.
In the 84-week clinical trial, 7 patients (4.6%) discontinued treatment because of adverse reactions. Adverse reactions leading to discontinuation included: hematocrit increased, estradiol increased, prostatic specific antigen increased, prostate cancer, mood swings, prostatic dysplasia, acne, and deep vein thrombosis.
Postmarketing Experience
Pulmonary Oil Microembolism (POME) and Anaphylaxis
Serious pulmonary oil microembolism (POME) reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL) in post-approval use outside the United States.
In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate in post-approval use outside of the United States.
DRUG INTERACTIONS
Insulin - Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.
Oral Anticoagulants - Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.
Corticosteroids - The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease.
USE IN SPECIFIC POPULATIONS
Geriatric Use - There have not been sufficient numbers of geriatric patients in controlled clinical studies with AVEED® to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. There are insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer.
DRUG ABUSE
AVEED® contains testosterone undecanoate, a Schedule III controlled substance in the Controlled Substances Act. Anabolic steroids, such as testosterone, are abused. Abuse is often associated with adverse physical and psychological effects.