新型拟钙剂Parsabiv(Etelcalcetide)静脉注射剂为12年来首个治疗：继发性甲状旁腺功能亢进 近日，新型拟钙剂Parsabiv(etelcalcetide)是美国生物技术巨头安进（ Amgen）开发的新一代肾脏病药物，获FDA批准用于血液透析成年患者继发性甲状旁腺功能亢进的治疗，本品也是12年来首个获批用于治疗血液透析及继发性甲状旁腺功能亢进的药物。 批准日期：2017年2月7日；公司：Amgen Inc PARSABIV(etelcalcetide)注射液，为静脉使用 美国初次批准：2017 作用机制 Etelcalcetide是一种拟钙剂[calcimimetic agent]别构作用地调节钙敏感受体(CaSR)。Etelcalcetide结合至CaSR和通过细胞外钙增强受体的活化。CaSR的活化对甲状旁腺主细胞减低PTH分泌。 适应证和用途 PARSABIV是一种钙敏感受体激动剂适用为： ● 继发性甲状旁腺功能亢进(HPT)在成年患者有慢性肾病(CKD)用血液透析。 使用的限制： PARSABIV尚未曽在患者有甲状旁腺癌，原发性甲状旁腺功能亢进，或有CKD是不用血液透析成年中研究和是不推荐为这些人群中使用。 剂量和给药方法 ● 确保校正的血清钙是处于或高于正常低限开始前，剂量增加，或再-开始。 ● 推荐开始剂量是通过静脉推注注射液5mg给予每周三次在血液透析治疗结束时。 ● 维持剂量是个体化和被滴定调整根据甲状旁腺激素(PTH)决定和校正的血清钙反应。这个剂量范围是2.5至15mg每周三次。 ● 这个剂量可能被增加以2.5mg或5mg增量不频于每4周。 ● 开始或剂量调整后1周内测量血清钙和每4周为维持。 ● 从开始或剂量调整测量后4周测量PTH。 ● 减低或暂时地终止PARSABIV，在个体有PTH水平低于目标范围。 ● 考虑减低或暂时地终止PARSABIV或使用同时治疗增加校正的血清钙在有一个校正的血清钙低于正常低限单处于或高于7.5mg/dL低钙血症的无症状患者。 ● 终止PARSABIV和治疗低钙血症如校正的血清钙下降低于7.5mg/dL或患者报告低钙血症症状。 ● 给药前不要混合或稀释。 ● 在冲洗后或静脉内冲洗后期间血液透析的结束时通过静脉推注注射液给入至透析环路静脉线。 剂型和规格 ● 注射液：2.5mg/0.5mL溶液在一个单剂量小瓶中 ● 注射液：5mg/mL溶液在一个单剂量小瓶中 ● 注射液：10mg/2mL溶液在一个单剂量小瓶中 禁忌证 PARSABIV是禁忌在患者对etelcalcetide或它的赋形剂的任何有已知的超敏性。 警告和注意事项 ● 低钙血症有时严重。严重的低钙血症可能致皮肤感觉异常，肌痛，肌肉痉挛，癫痫，QT 延长，和室性心律失常。患者易患QT间期延长，室性心律失常，和癫痫可能处于增加风险和需要严密监视。教育患者对低钙血症的症状和建议如他们发生联系卫生保健提供者。 ● 恶化的心衰校正的血清钙中减低可能伴随充血性心衰，但是，不能完全地排除与PARSABIV一个因果相互关系。严密地监视患者对心衰的恶化的体。 ● 上胃肠(GI)出血患者对上GI出血风险因子患者可能是处于增加风险。监视患者和及时地评价和治疗任何怀疑的GI出血。 ● 可能发生无力的骨[Adynamic Bone] 如PTH水平被慢性地抑制，如PTH水平减低低于推荐的目标范围，PARSABIV的剂量应被减低或终止。 不良反应 最常见不良反应(≥ 5%)为血钙减低，肌肉痉挛，腹泻，恶心，呕吐，头痛，低钙血症，和感觉异常。 特殊人群中使用 哺乳：当哺乳喂养时建议不使用PARSABIV。 供应/贮存和处置 PARSABIV(etelcalcetide)注射液被供应在一个单剂量小瓶中(型I玻璃)有塞子(氟聚合物层压弹性体)和一个铝封易拉防尘盖含5mg/mL的etelcalcetide作为一个 随时可用的透明和无色溶液在以下强度规格： 贮存 在冰箱贮存在原始纸盒在2°C至8°C(36°F至46°F)以避光保护。一旦从冰箱取出： ● 不要暴露至温度高于25°C(77°F). ● 如贮存在原始纸盒中在7天内使用。 ● 如从原始纸盒中取出，在4小时内使用和不要暴露于直接阳光。 FDA Approves Amgen's Parsabiv™ (Etelcalcetide), First New Treatment In More Than A Decade For Secondary Hyperparathyroidism In Adult Patients On Hemodialysis ' U.S. Food and Drug Administration (FDA) has approved Parsabiv (etelcalcetide) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Parsabiv is the first therapy approved for this condition in 12 years and the only calcimimetic that can be administered intravenously by the dialysis health care team three times a week at the end of the hemodialysis session. We are excited about today's approval of Parsabiv in the U.S. and the opportunity to provide patients and health care providers with a novel option to help treat a complex disease that affects a significant number of patients on hemodialysis," said Sean E. Harper, M.D.executive vice president of Research and Development at Amgen. "Parsabiv not only has demonstrated strong efficacy in clinical trials; it also fills an unmet need by putting the delivery of the therapy in the hands of the health care professional." Phase 3 Studies The approval of Parsabiv in the U.S. was largely based on data from two placebo-controlled Phase 3 studies, both of which met their primary endpoints. In the two 26-week, randomized, double-blind, placebo-controlled studies, an aggregate of 1,023 patients with moderate-to-severe secondary HPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week, at the end of their dialysis sessions in addition to standard of care that could include vitamin D and/or phosphate binders. The primary endpoint of both studies was the proportion of patients achieving greater than 30 percent reduction from baseline in PTH during the Efficacy Assessment Phase (EAP), defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300 pg/mL during the EAP; and percent reductions in PTH, albumin-adjusted calcium (cCa), phosphate (P) and cCa x P during the EAP. The two studies showed that significantly more Parsabiv than placebo patients, respectively, achieved: •A greater than 30 percent reduction from baseline in PTH during the EAP: 77 percent versus 11 percent in Study 1, and 79 percent versus 11 percent in Study 2 •PTH levels of 300 pg/mL or less during the EAP: 52 percent versus 6 percent in Study 1, and 56 percent versus 5 percent in Study 2 Additionally, greater percent reduction from baseline was achieved in Parsabiv-treated patients than placebo-treated patients during the EAP, for PTH, corrected calcium and phosphate in both studies. In a pooled analysis of the two Phase 3 placebo-controlled studies, asymptomatic reductions in serum calcium and symptomatic hypocalcemia occurred more frequently in patients treated with Parsabiv compared to placebo (64 percent versus 10 percent, and 7 percent versus 0.2 percent, respectively). Other commonly reported adverse reactions were muscle spasms (12 percent versus 7 percent), diarrhea (11 percent versus 9 percent), nausea (11 percent versus 6 percent), vomiting (9 percent versus 5 percent), headache (8 percent versus 6 percent), and paresthesia/hypoesthesia (6 percent versus 1 percent). About Secondary Hyperparathyroidism Secondary hyperparathyroidism (HPT) is a chronic and serious condition which affects many of the approximately two million people throughout the world who are receiving dialysis, including 468,000 people in the U.S.Approximately 88 percent of CKD patients on hemodialysis will develop secondary HPT.Secondary HPT refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to decreased renal function and impaired mineral metabolism. The elevated levels of PTH can lead to an increase in the release of calcium and phosphate from the bones.Secondary HPT is often initially silent and asymptomatic.As a result, secondary HPT is frequently underdiagnosed and undertreated. About Parsabiv™ (etelcalcetide) in the U.S.Parsabiv is a novel calcimimetic agent indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Parsabiv has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations. A calcimimetic is a drug that mimics the action of calcium by activating the calcium-sensing receptors on the parathyroid gland. Parsabiv binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby decreasing PTH levels. Parsabiv Important Safety Information in the U.S. Contraindication: Parsabiv™ is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred. Hypocalcemia: Parsabiv™ lowers serum calcium and can lead to hypocalcemia, sometimes severe. Significant lowering of serum calcium can cause QT interval prolongation and ventricular arrhythmia.  Patients with conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv. Closely monitor corrected serum calcium and QT interval in patients at risk on Parsabiv™. Significant reductions in corrected serum calcium may lower the threshold for seizures. Patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to Parsabiv™.   Monitor corrected serum calcium in patients with seizure disorders on Parsabiv™. Concurrent administration of Parsabiv™ with another oral calcimimetic could result in severe, life-threatening hypocalcemia. Patients switching from cinacalcet to Parsabiv™ should discontinue cinacalcet for at least 7 days prior to initiating Parsabiv™. Closely monitor corrected serum calcium in patients receiving Parsabiv™ and concomitant therapies known to lower serum calcium.  Measure corrected serum calcium prior to initiation of Parsabiv™. Do not initiate in patients if the corrected serum calcium is less than the lower limit of normal. Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every weeks during treatment with Parsabiv™. Measure PTH weeks after initiation or dose adjustment of Parsabiv™. Once the maintenance dose has been established, measure PTH per clinical practice. Worsening Heart Failure: In Parsabiv™ clinical studies, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. Closely monitor patients treated with Parsabiv™ for worsening signs and symptoms of heart failure. Upper Gastrointestinal Bleeding: In clinical studies, 2 patients treated with Parsabiv™ in patient years of exposure had upper gastrointestinal (GI) bleeding at the time of death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether these cases were related to Parsabiv™. Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv™. Monitor patients for worsening of common Parsabiv™ GI adverse reactions and for signs and symptoms of GI bleeding and ulcerations during Parsabiv™ therapy.  Adynamic Bone: Adynamic bone may develop if PTH levels are chronically suppressed.  Adverse Reactions: In clinical trials of patients with secondary HPT comparing Parsabiv™ to placebo, the most common adverse reactions were blood calcium decreased (64% vs. 10%), muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea (11% vs 6%), vomiting (9% vs 5%), headache (8% vs 6%), hypocalcemia (7% vs 0.2%), and paresthesia (6% vs 1%). This article Department of pharmacists/medical experts original translation finishing, welcome to reprint! At the same time the procurement of domestic scientific research institutions can contact us: 2363244352.3330889895