EDARBYCLOR (azilsartan medoxomil and chlorthalidone) Now Available in

U.S. Pharmacies for Patients with Hypertension

DEERFIELD, Ill., and OSAKA, Japan, Feb. 6, 2012 /PRNewswire/ -- Takeda

Pharmaceutical Company Limited (Takeda) and its wholly-owned

subsidiary, Takeda Pharmaceuticals U.S.A., Inc., today announced

EDARBYCLOR (azilsartan medoxomil and chlorthalidone) is now available

by prescription in U.S. pharmacies for the treatment of hypertension

to lower blood pressure in adults. It is the only fixed-dose therapy

in the U.S. to combine an angiotensin II receptor blocker (ARB) with

chlorthalidone in a once-daily, single tablet. In a phase 3 clinical

trial, the systolic blood pressure reductions of the maximum dose of

EDARBYCLOR (40/25 mg), by both clinic and trough 24-hour ambulatory

blood pressure monitoring, were shown to be statistically superior to

those of the fixed-dose combination of olmesartan

medoxomil-hydrochlorothiazide at its maximum dose (40/25 mg).

Additionally, similar blood pressure lowering effects of EDARBYCLOR

were observed in a sub-group analysis of black patients.

EDARBYCLOR is a fixed-dose combination of two medications: azilsartan

medoxomil, an ARB, and chlorthalidone, a long-acting diuretic used in

the treatment of hypertension. Azilsartan medoxomil is approved under

the trade name EDARBI in the U.S., Europe and Mexico. The two

medications work to help lower blood pressure levels in patients with

hypertension. EDARBYCLOR was approved by the U.S. Food and Drug

Administration on December 20, 2011, at a recommended starting dose of

40/12.5 mg and a maximal dose of 40/25 mg.

Lowering blood pressure reduces the risk of fatal and nonfatal

cardiovascular events, primarily strokes and heart attacks. There are

no controlled trials of EDARBYCLOR demonstrating reductions in

cardiovascular risk in patients with hypertension; however, trials

with chlorthalidone and at least one drug similar to azilsartan

medoxomil have demonstrated such benefits.

"February is American Heart Month and it's important to recognize that

nearly 40 percent of hypertension patients are not at their blood

pressure targets, putting them at increased cardiovascular risk," said

Douglas Cole, president, Takeda Pharmaceuticals U.S.A., Inc. "We're

pleased to bring EDARBYCLOR to market and expand the EDARBI family of

products to help appropriate patients with hypertension work towards

reaching their blood pressure goals."

About Hypertension Hypertension, or high blood pressure, is a chronic

medical condition in which blood pressure is elevated to levels of 140

mm Hg or greater systolic and/or 90 mm Hg or greater diastolic.

Elevated systolic or diastolic pressure causes increased

cardiovascular risk, and the absolute risk increase per mm Hg is

greater at higher blood pressures, so that even modest reductions of

severe hypertension can provide substantial benefit. Control of high

blood pressure should be part of comprehensive cardiovascular risk

management including, as appropriate, lipid control, management of

diabetes, prevention of blood clots, smoking cessation, exercise and

limited sodium intake.

Hypertension impacts approximately 76 million Americans, or nearly one

in three adults. It is estimated that nearly one billion people are

affected by hypertension worldwide, and this figure is predicted to

increase to 1.5 billion by 2025. Hypertension typically has no

symptoms. Adults of all ages and backgrounds can develop hypertension;

however, the risk of developing the condition increases with age, with

more than half of people over age 60 affected. Hypertension is also

costly to the nation's health care system. The American Heart

Association recently estimated that direct and indirect expenses

associated with hypertension cost the nation more than $73 billion in


About EDARBI and EDARBYCLOR EDARBI (azilsartan medoxomil) is an

angiotensin II receptor blocker (ARB) developed by Takeda for the

treatment of hypertension to lower blood pressure in adults. EDARBI

lowers blood pressure by blocking the action of angiotensin II, a

vasopressor hormone, which naturally exists within the body. When

EDARBI blocks the angiotensin II receptor, blood vessels can stay

relaxed and open, and blood pressure can be reduced. EDARBI is

indicated for the treatment of hypertension to lower blood pressure in

adults, either alone or in combination with other antihypertensive

agents. The recommended dose of EDARBI in adults is 80 mg taken once

daily. A starting dose of 40 mg may be appropriate for patients on

high doses of diuretics. EDARBI is approved in the United States,

Europe and Mexico.

EDARBYCLOR (azilsartan medoxomil and chlorthalidone) is a fixed-dose

combination therapy for the treatment of hypertension that combines

azilsartan medoxomil and chlorthalidone in a single tablet.

Chlorthalidone reduces the amount of water in the body by increasing

the flow of urine, which helps lower blood pressure. EDARBYCLOR is

indicated for the treatment of hypertension to lower blood pressure;

it may be used in patients not adequately controlled with monotherapy

and as an initial therapy if a patient is likely to need multiple

drugs to achieve blood pressure goals. The recommended starting dose

of EDARBYCLOR in adults is 40/12.5 mg taken orally once daily. The

maximal dose is 40/25 mg.

Important Safety Information Boxed Warning for FETAL TOXICITY

When pregnancy is detected, patients should discontinue EDARBI or

EDARBYCLOR as soon as possible. Drugs that act directly on the

renin-angiotensin system can cause injury and death to the developing


EDARBYCLOR is contraindicated in patients with anuria.

Use of drugs that act on the renin-angiotensin system during the

second and third trimesters of pregnancy reduces fetal renal function

and increases fetal and neonatal morbidity and death. When pregnancy

is detected, patients should discontinue EDARBI or EDARBYCLOR as soon

as possible. Thiazides cross the placental barrier and appear in cord

blood and may be associated with adverse reactions, including fetal or

neonatal jaundice and thrombocytopenia.

In patients with an activated renin-angiotensin-aldosterone system

(RAAS), such as volume- and/or salt-depleted patients, EDARBI and

EDARBYCLOR can cause excessive hypotension. Correct volume or salt

depletion prior to administration of EDARBI or EDARBYCLOR.

Patients with renal impairment should be monitored for worsening renal

function. In patients whose renal function may depend on the activity

of the renin-angiotensin system, treatment with ACE inhibitors and

ARBs has been associated with oliguria or progressive azotemia and

rarely with acute renal failure and death. In patients with renal

artery stenosis, EDARBI and EDARBYCLOR may cause renal failure. In

patients with renal disease, chlorthalidone may precipitate azotemia.

Consider withholding or discontinuing EDARBI or EDARBYCLOR if

progressive renal impairment becomes evident.

Hypokalemia is a dose-dependent adverse reaction that may develop with

chlorthalidone. Coadministration of digitalis may exacerbate the

adverse effects of hypokalemia. EDARBYCLOR attenuates

chlorthalidone-associated hypokalemia.

Hyperuricemia may occur or frank gout may be precipitated in certain

patients receiving chlorthalidone or other thiazide diuretics.

The most common adverse reaction that occurred more frequently with

EDARBI than placebo in adults was diarrhea (2 percent versus 0.5

percent). The adverse reactions that occurred at an incidence of

greater than or equal to 2 percent of EDARBYCLOR-treated patients, and

greater than azilsartan medoxomil or chlorthalidone, were dizziness

(8.9 percent) and fatigue (2.0 percent). The incidence of consecutive

elevations of creatinine with EDARBYCLOR (greater than or equal to 50

percent from baseline and greater than the upper limit of normal) was

2 percent; elevations were typically transient, or nonprogressive and

reversible, and associated with large blood pressure reductions. With

EDARBI 80 mg, small reversible increases were seen.

Renal clearance of lithium is reduced by diuretics, such as

chlorthalidone, increasing the risk of lithium toxicity. Patients

receiving EDARBI or EDARBYCLOR and nonsteroidal anti-inflammatory

drugs (NSAIDs) who are also elderly, volume-depleted (including those

on diuretics), or who have compromised renal function due to potential

reversible deterioration of renal function should have their renal

function monitored periodically. NSAIDs may interfere with

antihypertensive effect.

For further information:

Please click here for complete EDARBI Prescribing Information or here

for complete EDARBYCLOR Prescribing Information.

Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research &

Development Center, Inc. Based in Deerfield, Ill., Takeda

Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development

Center, Inc. are subsidiaries of Takeda Pharmaceutical Company

Limited, the largest pharmaceutical company in Japan. The respective

companies currently market oral diabetes, insomnia, rheumatology, and

gastroenterology and cardiovascular treatments and seek to bring

innovative products to patients through a pipeline that includes

compounds in development for metabolic and cardiovascular disease,

gastroenterology, neurology and other conditions. To learn more about

these Takeda companies, visit

About Takeda Pharmaceutical Company Limited Located in Osaka, Japan,

Takeda is a research-based global company with its main focus on

pharmaceuticals. As the largest pharmaceutical company in Japan and

one of the global leaders of the industry, Takeda is committed to

strive towards better health for patients worldwide through leading

innovation in medicine. Additional information about Takeda is

available through its corporate website,


Ashleigh Duchene GolinHarris 312-729-4428

Jocelyn Gerst Takeda Pharmaceuticals U.S.A., Inc. 224-554-5542

Corporate Communications Dept. Takeda Pharmaceutical Company Limited


SOURCE Takeda Pharmaceutical Company Limited

-0- 02/06/2012

/Web Site:

CO: Takeda Pharmaceutical Company Limited; Takeda Pharmaceuticals U.S.A., Inc.

ST: Illinois Japan




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