摘要

BACKGROUND:Desmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin. METHODS AND FINDINGS:We conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)-matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135-145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin. CONCLUSIONS:Use of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.

译文

背景: 去氨加压素于 1978年被美国食品和药物管理局 (FDA) 批准用于尿崩症和出血性疾病,但也为夜尿患者开了标签。量化成年患者服用去氨加压素的潜在风险变得更加重要,因为一种新的鼻内去氨加压素制剂于 2017年获得美国食品和药物管理局的批准。像旧的配方一样,主要的活性成分是醋酸去氨加压素,但是新配方也含有一种旨在增强吸收的赋形剂。我们的目的是量化在常规临床护理中使用旧配方去氨加压素的患者的低钠血症发生率。方法和结果: 我们从 2006年2月1日到 2017年2月1日使用全国商业健康计划数据库进行了一项基于人群的新用户队列研究。新开药较老的去氨加压素配方的患者的倾向评分 (PS) 与新开药奥昔布宁的患者相匹配。作为敏感性分析,坦索罗辛被用作比较器而不是奥昔布宁。主要结果是低钠血症的主要诊断。1:1 PS 匹配后的比例风险模型用于估计风险比 (HRs) 和 95% 置信区间 (CI)。我们确定了 3,137 名新服用去氨加压素的成年人,并将他们与 3,137 名新服用奥昔布宁的成年人进行了匹配。平均年龄为 70 岁,55% 为男性,13% 在基线时间内为利尿剂配药, 在接受任何一种研究药物之前,平均基线钠浓度为 140 mmol/L (正常: 135-145)。服用去氨加压素的成年人的低钠血症比率为每 146 人年 1,000,而服用奥昔布宁的成年人的低钠血症比率为每 1,000 人年 11,相当于高 13 倍 (HR 13.19; 95% CI 6.69,26.01; p <0.01)。当随访在 30 天被截断时,观察到类似的增加率 (HR 19.41; 95% CI 7.11,52.99; p & lt; 0.01)。当坦索罗辛为对照时,去氨加压素的低钠血症发生率也更高 (HR 12.10; 95% CI 6.54,22.37; p <0.01)。我们研究的重要限制包括未测量的混杂 (例如,非处方药的使用,饮食摄入),缺失的数据 (例如,只有 20% 的患者有基线血清钠), 以及缺乏关于去氨加压素新制剂的数据。结论: 使用较旧的去氨加压素制剂与使用其他治疗下泌尿系统症状的药物相比,随后的低钠血症发生率显著增加。这种风险应该清楚地传达给开了这种去氨加压素制剂的患者。

Desmopressin

神经 尿崩症 治疗药物
概述  :  

去氨加压素系人工合成的环状九肽,巯基丙酰-L-酪氨酰-L-苯丙氨酰-L-谷氨酰氨酰-L-天冬酰氨酰-L-半胱氨酰-L-脯氨酰-D-精氨酰-L-甘氨酰氨,类似于抗利尿激素(ADH)。去氨加压素是治疗夜尿症以及中枢性尿崩症的一线替代治疗药物。适应证 ①在介人性治疗或诊断性手术前,用于先天性或药物诱发的血小板功能障碍、尿毒症、肝硬化及不明原因引起的出血时间延长,使延长的出血时间缩短或恢复正常。②对本品试验剂量呈阳性反应的轻度甲型血友病及血管性血友病的患者,可用于控制及预防小型手术时的出血,甚至对中

desmopressin

释    义   n. 去氨加压素

例    句   All intranasal formulations of desmopressin are now contraindicated for the treatment of PNE. 从现在开始去氨加压素所有鼻腔用剂型都禁忌用于PNE。

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