帕立骨化醇（paricalcitol 商品名：Zemplar）是雅培研发的一种维生素D类似物。帕立骨化醇注射液获得FDA批准，适用于预防和治疗与慢性肾病5期相关的继发性甲状旁腺功能亢进症。
批准日期：1998年4月17日 公司：雅培公司
ZEMPLAR（帕立骨化醇[paricalcitol]）注射液，用于静脉注射
最初的美国批准：1998年
作用机制
帕立骨化醇是一种合成的，具有生物活性的维生素D2类似物。临床前和体外研究表明，帕立骨化醇的生物学作用是通过维生素D受体（VDR）的结合介导的，这导致维生素D反应途径的选择性激活。已显示维生素D和帕立骨化醇通过抑制PTH合成和分泌来降低PTH水平。
适应症和用法
ZEMPLAR是一种维生素D类似物，用于预防和治疗5岁及以上患有透析的慢性肾病患者的继发性甲状旁腺功能亢进。
剂量和给药
开始前确保血清钙不超过正常上限。
在透析期间的任何时间通过血液透析血管通路静脉内施用ZEMPLAR。
成人剂量：
以每隔一天开始0.04mcg/kg至0.1mcg/kg（2.8mcg至7mcg）的频率开始。
将维持剂量靶向所需治疗范围内的完整甲状旁腺激素（PTH）水平和正常范围内的血清钙。
在剂量开始或调整后每2至4周经常监测血清钙（例如每周两次）和完整的PTH水平。
基于完整PTH水平的滴定建议的完整处方信息参见表1。
暂停或减少持续异常低完整PTH或血清钙的剂量始终高于正常范围。
儿科剂量：
启动ZEMPLAR作为静脉推注剂量：
如果基线完整PTH小于500pg/mL，则为0.04mcg/kg，或
如果基线完整PTH为500pg/mL或更高，则为0.08mcg/kg。
将维持剂量靶向所需治疗范围内的完整PTH水平和正常范围内的血清钙。
在剂量开始或调整后每2至4周经常监测血清钙（例如每周两次）和完整的PTH水平。
有关基于完整PTH水平的滴定建议的完整处方信息，请参见表2。
暂停或减少持续异常低完整PTH或血清钙的剂量始终高于正常范围。
剂量形式和强度
ZEMPLAR可用作：
注射：2mcg/mL单剂量小瓶
注射：5mcg/mL单剂量小瓶
注射：10mcg/2mL（5mcg/mL）多剂量小瓶
禁忌症
高钙血症
维生素D毒性
已知对帕立骨化醇或任何非活性成分的超敏反应。
警告和注意事项
高钙血症：在使用ZEMPLAR治疗期间可能发生，并可导致心律失常和癫痫发作。严重的高钙血症可能需要紧急注意。当ZEMPLAR与高剂量钙制剂，噻嗪类利尿剂或维生素D化合物同时使用时，风险可能会增加。告知患者高钙血症的症状，并在开始前和治疗期间监测血清钙，并相应地调整剂量。
洋地黄毒性：高钙血症会增加风险。在使用洋地黄化合物的患者中，监测血清钙和患者的洋地黄毒性症状和体征。在开始或调整ZEMPLAR剂量时更频繁地监测。
Adynamic Bone Disease：如果完整PTH水平被抑制到异常低水平，可能会发展并增加骨折风险。监测完整的PTH水平并根据需要调整剂量。
不良反应
最常见的不良反应（>5％且比安慰剂更频繁）是恶心，呕吐和水肿。
要报告疑似不良反应，请致电1-800-633-9110联系AbbVie Inc.或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
强CYP3A抑制剂：与强CYP3A抑制剂（例如酮康唑）共同给药增加了ZEMPLAR暴露。可能需要调整剂量。密切监测完整的PTH和血清钙。
包装提供/存储和处理
ZEMPLAR注射液是一种透明，无色的溶液，可在25个样品瓶的托盘中使用，如下所示：
总强度    每毫升强度  样品瓶容量和样品瓶类型   NDC
2mcg/mL    2mcg/mL      1mL单剂量小瓶        0074-4637-01
5mcg/mL    5mcg/mL      1mL单剂量小瓶        0074-1658-01
10mcg/2mL  5mcg/mL      2mL多剂量小瓶        0074-1658-05
储存在25°C（77°F）。 允许的偏差在15°至30°C（59°至86°F）之间。
使用后丢弃单剂量小瓶的任何未使用部分。
在初始使用后，当在受控的室温下储存时，多剂量小瓶的内容物保持稳定长达七天。
完整说明书附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7259652F-81BC-4AD1-BBA5-D01F9FAC1B80
Zemplar (Paricalcitol Tablets)
ZEMPLAR- paricalcitol capsule, liquid filled
AbbVie Inc.
1 INDICATIONS AND USAGE
1.1 Chronic Kidney Disease Stages 3 and 4
ZEMPLAR capsules are indicated in adults and pediatric patients 10 years of age and older for the prevention and treatment of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 and 4.
1.2 Chronic Kidney Disease Stage 5
ZEMPLAR capsules are indicated in adults and pediatric patients 10 years of age and older for the prevention and treatment of secondary hyperparathyroidism associated with CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD).
2 DOSAGE AND ADMINISTRATION
2.1 Chronic Kidney Disease Stages 3 and 4 in Adults
Administer ZEMPLAR capsules orally once daily or three times a week [see Clinical Studies].
When dosing three times weekly, do not administer more frequently than every other day.
2.2 Chronic Kidney Disease Stage 5 in Adults
Initial Dose
Administer the dose of ZEMPLAR capsules orally three times a week, no more frequently than every other day based upon the following formula:
Dose (micrograms) = baseline iPTH (pg/mL) divided by 80
Treat patients only after their baseline serum calcium has been adjusted to 9.5 mg/dL or lower to minimize the risk of hypercalcemia[see Clinical Pharmacology and Clinical Studies].
Dose Titration
Individualize the dose of ZEMPLAR based on iPTH, serum calcium and phosphorus levels. Titrate ZEMPLAR dose based on the following formula:
Dose (micrograms) = most recent iPTH level (pg/ml) divided by 80
If serum calcium is elevated, the dose should be decreased by 2 to 4 micrograms.
As iPTH approaches the target range, small, individualized dose adjustments may be necessary in order to achieve a stable iPTH. In situations where monitoring of iPTH, Ca or P occurs less frequently than once per week, a more modest initial and dose titration ratio (e.g., iPTH divided by 100) may be warranted.
2.3 Pediatric Patients (Ages 10 to 16 Years)
CKD Stages 3 and 4
Initial Dose
Administer ZEMPLAR 1 mcg capsule orally three times a week, no more frequently than every other day.
Dose Titration
Individualize and titrate ZEMPLAR dose based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range.
Every 4 weeks, each administered ZEMPLAR dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., increase from 1 mcg three times per week to 2 mcg three times per week). At any time, each administered dose may be decreased by 1 mcg. ZEMPLAR may be stopped if the patient requires reduction while receiving 1 mcg three times per week, resuming when appropriate.
CKD Stage 5
Initial Dose
Administer the dose of ZEMPLAR capsules orally three times a week, no more frequently than every other day based upon the following formula:
Dose* (micrograms) = baseline iPTH (pg/mL) divided by 120 * Round down to the nearest whole number
Dose Titration
Subsequent dosing should be individualized and based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range.
Every 4 weeks, each administered ZEMPLAR dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., increase from 1 mcg three times per week to 2 mcg three times per week). At any time, each administered dose may be decreased by 2 mcg.
ZEMPLAR may be stopped if the patient requires reduction while receiving 2 mcg three times per week or 1 mcg three times per week, resuming when appropriate.
DESCRIPTION
Paricalcitol, USP, the active ingredient in ZEMPLAR capsules, is a synthetically manufactured, metabolically active vitamin D analog of calcitriol with modifications to the side chain (D2 ) and the A (19-nor) ring. ZEMPLAR is available as soft gelatin capsules for oral administration containing 1microgram or 2micrograms of paricalcitol.
Each capsule also contains medium chain triglycerides, alcohol, and butylated hydroxytoluene. The medium chain triglycerides are fractionated from coconut oil or palm kernel oil.
The capsule shell is composed of gelatin, glycerin, titanium dioxide, iron oxide red (2 microgram capsules only), iron oxide yellow (2 microgram capsules only), iron oxide black (1 microgram capsules only), and water.
Paricalcitol is a white, crystalline powder with the empirical formula of C27 H44 O3 , which corresponds to a molecular weight of 416.64. Paricalcitol is chemically designated as 19-nor-1?,3,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-triene
CLINICAL PHARMACOLOGY
Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin as vitamin D3 and from dietary intake as either vitamin D2 or D3 . Both vitamin D2 and D3require two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR).
The endogenous VDR activator, calcitriol[1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone.
In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis. Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy.
12.1 Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have demonstrated that paricalcitol�s biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.