快樂小藥師 Im pharmacist nichts glücklich

Indication and Clinical Profile^1,2

Azilsartan is the newest angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension, alone or in combination with other antihypertensive agents. Hypertension, defined as systolic/diastolic blood pressure (BP) of ≥140 mmHg/90 mmHg, affects approximately 75 million Americans and is associated with increased risk of stroke, heart failure, heart attack, renal failure (RF), and death. Drugs that block the renin-angiotensin system, including ARBs, ACE inhibitors, and renin inhibitors, have become standard treatments for hypertension.

The efficacy of azilsartan was demonstrated by seven phase III clinical trials (placebo-controlled and active comparator-controlled) involving more than 5,900 patients. These trials showed that azilsartan was statistically superior to placebo and active comparators (olmesartan and valsartan) in the reduction of BP measurements at endpoint.

Pharmacology and Pharmacokinetics^1,2

Azilsartan is a benzimidazole ester (FIGURE 1) that inhibits the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the angiotensin type 1 (AT1) receptor in many tissues, such as vascular smooth muscle and the adrenal gland. The angiotensin type 2 (AT2) receptor is also found in many tissues, but it is not known to be associated with cardiovascular homeostasis. Azilsartan has a >10,000-fold greater affinity for the AT1 receptor than for the AT2 receptor. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of azilsartan on BP.

Azilsartan medoxomil is rapidly hydrolyzed to azilsartan, the active metabolite, in the gastrointestinal (GI) tract during absorption. The estimated absolute bioavailability of azilsartan is approximately 60% and is not affected by food. Azilsartan is metabolized by O-dealkylation by CYP2C9 (metabolite M-II) and decarboxylation (metabolite M-I). M-I and M-II do not contribute to the drug's pharmacologic activity. Azilsartan is eliminated in the urine and feces, mainly as metabolites.

Adverse Reactions and Drug Interactions^1,2

Adverse reactions to azilsartan in clinical trials were similar to those reported by subjects taking placebo. The most common adverse reactions were dizziness, increased blood creatine phosphokinase, and diarrhea. Azilsartan medoxomil has a black box warning stating that the drug should be avoided during the second and third trimesters of pregnancy because it can cause fetal injury or death (Pregnancy Category D). If a woman becomes pregnant while using azilsartan, the drug should be discontinued as soon as possible. In patients with an activated renin-angiotensin system, as by volume or salt depletion, ARBs can cause excessive hypotension; therefore, volume or salt depletion should be corrected prior to administration. ARBs can cause RF in susceptible patients (e.g., renal artery stenosis), so renal function should be monitored in patients with renal impairment.

Coadministration of nonsteroidal antiinflammatory drugs (NSAIDs) and ARBs may result in a deterioration in renal function, including possible acute RF, as well as a decreased antihypertensive effect of the ARB.

Dosage and Administration^1,2

Azilsartan is supplied as 40-mg and 80-mg tablets. The recommended dose is 80 mg once daily; the 40-mg dose may be used in patients taking high-dose diuretics. No initial dosage adjustment is recommended for elderly patients or in patients with mild-to-severe renal impairment, end-stage renal disease, or mild-to-moderate hepatic dysfunction. Azilsartan has not been studied in patients with severe hepatic impairment. If BP is not controlled with azilsartan alone, additional BP reduction may be achieved through the addition of other antihypertensives.

降血壓藥物機轉：

圖解藥理學 18 血壓用藥06

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美國食品和藥物管理局批准Edarbi錠（azilsartan medoxomil）用於治療成年人高血壓。

臨床研究數據顯示，與FDA批准的其他兩種高血壓藥物，Diovan (valsartan) 及 Benicar (olmesartan) 比較，Edarbi更有效地降低24小時血壓。

“高血壓常被稱為'沉默殺手'，因為它通常沒有症狀，直到它造成身體損害，”FDA藥物評估和研究中心心血管和腎臟藥物產品部主任Norman Stockbridge博士說，“許多人確診為高血壓後，仍然控制不佳，因此有多種治療選項是很重要的。”

Edarbi將有80毫克和40毫克的劑量，推薦劑量定在80毫克，每天一次。 40毫克的劑量將用於使用高劑量利尿劑減少體內鹽份的病人。

血壓是心臟抽吸血液後衝擊動脈壁的力量。如果血壓上升且一直居高不下，它會在許多方面破壞身體。近三分之一的美國成年人有高血壓，它會增加中風、心力衰竭、心臟病發作、腎臟衰竭的風險，甚至死亡。

Edarbi是angiotensinⅡ受體阻斷劑（angiotensin II receptor blocker，ARB），它藉由阻斷angiotensinⅡ(一種血管收縮激素)的作用而降低血壓。

臨床試驗中服用Edarbi患者報告的不良反應和服用安慰劑者報告的類似。

Edarbi有黑框警告，指出該藥物應避免在孕婦使用，因為在第二或第三孕期使用該藥物會造成傷害，甚至胎兒死亡。當婦女使用該藥物時，如果懷孕了，應該盡快停止使用。

Edarbi是由伊利諾伊州，武田製藥北美迪爾菲爾德製造。