FDA已经批准Edarbyclor（azilsartan沙坦和氯噻酮）用于降低成人血压以治疗高血压。Edarbyclor是美国境内唯一的固定剂量疗法，该疗法结合了血管紧张素II受体阻滞剂和利尿剂氯噻酮。该疗法的建议初始计量为40/12.5mg，最大剂量为40/25mg。
该疗法两类药品都有降低血压的作用，azilsartan沙坦（美国商品名为EDARBI）通过阻滞血管紧张素II的活动达到降血压的效，一旦该药物阻滞了血管紧张素II得受体，人体血管就会变得松弛，血压自然会下降；氯噻酮通过提高尿量从而减少体内水量达到降压的效果，之前的临床试验均显示氯噻酮对高血压患者降低血压是有效果的，长期服用还可以减少高血压相关综合症。
高血压是一种极为复杂的疾病,可以引起一系列的并发症如中风和心脏病。Edarbyclor疗法的通过为适宜病人降低血压提供了额外有效的选择。
EDARBYCLOR
Manufacturer:
Takeda Pharmaceuticals North America, Inc.

Pharmacological Class:
Angiotensin II receptor blocker (ARB) + diuretic.

Active Ingredient(s):
Azilsartan medoxomil, chlorthalidone; 40/12.5mg, 40/25mg; tablets.

Indication(s):
Hypertension (HTN) in patients not adequately controlled with monotherapy. As initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Pharmacology:
Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II, a pressor agent, by selectively blocking the binding of angiotensin II to the AT1 receptor in tissues such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.

Chlorthalidone is a monosulfamyl thiazide-like diuretic that produces diuresis with increased excretion of sodium and chloride. The site of action appears to be the cortical diluting segment of the ascending limb of Henle’s loop of the nephron. Although the mechanism of action of chlorthalidone and related drugs is not fully understood, sodium and water depletion appear to provide a basis for its antihypertensive effect.

Clinical Trials:
The antihypertensive effects of azilsartan medoxomil and chlorthalidone have been demonstrated in a total of 5 randomized controlled studies, which included 4 double-blind, active-controlled studies and 1 open-label, long-term active-controlled study. The studies ranged from 8 weeks to 12 months in duration, at doses ranging from 20/12.5mg to 80/25mg once daily. A total of 5,310 patients (3,082 given azilsartan medoxomil and chlorthalidone and 2,228 given active comparator) with moderate or severe hypertension were studied.

An 8-week, randomized, double-blind, active-controlled, parallel group factorial trial in patients with moderate-to-severe hypertension compared the effect on blood pressure of azilsartan medoxomil and chlorthalidone with the respective monotherapies. The trial randomized 1,714 patients to one of 11 active treatment arms. The 6 treatment combinations of azilsartan medoxomil 20, 40, or 80mg and chlorthalidone 12.5 or 25mg resulted in statistically significant reduction in systolic and diastolic blood pressure as determined by ambulatory blood pressure monitoring and clinic measurement at trough compared with the respective individual monotherapies.

In a 12-week, double-blind forced titration trial, azilsartan medoxomil and chlorthalidone 40/25mg was statistically superior (P<0.001) to olmesartan medoxomil and hydrochlorothiazide 40/25mg in reducing systolic blood pressure in patients with moderate-to-severe hypertension.

Legal Classification:
Rx

Adults:
≥18 years: initially 40/12.5mg once daily. May increase to 40/25mg after 2–4 weeks as needed. Max: 40/25mg. Patients titrated to the individual components: may give corresponding dose of Edarbyclor. See literature.

Children:
<18 years: not recommended.

Contraindication(s):
Anuria.

Warnings/Precautions:
Correct salt/volume depletion before starting therapy; monitor for hypotension. Severe CHF. Renal artery stenosis. Hepatic or renal impairment. Monitor serum creatinine, BUN. Gout. Hypokalemia. Hyperuricemia. Pregnancy (Cat. D; avoid). Nursing mothers: not recommended.

Interaction(s):
May be antagonized by, and renal toxicity potentiated by NSAIDs, including selective COX-2 inhibitors (monitor renal function periodically in elderly and/or volume depleted). May increase toxicity of lithium. Digitalis may exacerbate hypokalemia.

Adverse Reaction(s):
Dizziness, fatigue, hypotension, syncope, serum creatinine increased.

How Supplied:
Tabs—30, 90

Last Updated:
1/23/2012

FDA批准新型Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)上市,用于治疗高血压
Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)由武田制药研制生产,由一种血管紧张素Ⅱ受体阻断剂(阿齐沙坦酯)与一种利尿剂(氯噻酮)组成的固定剂量的复方药物。Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)获准基于5项3期临床研究,总共涉及逾5000例高血压患者,这些研究历时8-52周不等,阿齐沙坦酯/氯噻酮的剂量范围是20/12.5-80/25mg,每日用药1次。
研究结果显示,Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂))治疗组患者的平均谷值(22-24h)收缩压(SBP)较单用阿齐沙坦酯或氯噻酮治疗组显著降低,其SBP也比接受最高获准剂量下的奥美沙坦酯/氯噻酮复方制剂治疗组患者显著降低。当患者需要使用多种降压药物治疗时,可将Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)作为初始治疗,其针对成人的推荐初始剂量为40/12.5mg,经口服用药,每日1次,最大推荐剂量为80/25mg。
Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)最常见的不良反应为眩晕和疲乏。肌酐水平的升高(2%)一般呈一过性,或是非进行性和可逆性,并伴有血压大幅下降。
由于肾功能可能依赖肾素-血管紧张素系统活动的患者采用血管紧张素转换酶(ACE)抑制剂和ARB治疗可引起少尿和氮质血症,在极少数情况下还可导致肾衰竭和死亡。有肾动脉狭窄的患者使用Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)可能会造成肾衰竭。而肾病患者使用氯噻酮可能会诱发氮质血症。因此,在患者出现进行性肾功能损害时,应考虑停止Edarbyclor(阿齐沙坦酯/氯噻酮复方制剂)治疗,以防其肾功能恶化。