FDA Approves EDARBYCLOR (azilsartan medoxomil and chlorthalidone) for the Treatment of Hypertension

DEERFIELD, Ill. and OSAKA, Japan, Dec. 20, 2011 /PRNewswire/ -- Takeda Pharmaceutical Company Limited (Takeda) and its wholly-owned subsidiary, Takeda Pharmaceuticals North America, Inc., announced today that the U.S. Food and Drug Administration (FDA) approved EDARBYCLOR (azilsartan medoxomil and chlorthalidone) for the treatment of hypertension to lower blood pressure in adults. EDARBYCLOR is the only fixed-dose therapy in the U.S. to combine an angiotensin II receptor blocker (ARB) with the diuretic chlorthalidone in a once-daily, single tablet. The recommended starting dose of EDARBYCLOR is 40/12.5 mg and the maximum dose is 40/25 mg.

The two medications in EDARBYCLOR work to help lower blood pressure in patients with hypertension. Azilsartan medoxomil, marketed as EDARBI in the U.S., reduces blood pressure by blocking the action of angiotensin II, a vasopressor hormone that 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. Chlorthalidone reduces the amount of water in the body by increasing the flow of urine, which helps to lower blood pressure. Prior landmark clinical outcomes trials have demonstrated that chlorthalidone is effective in reducing blood pressure in patients with hypertension and that long-term use is associated with reductions in serious hypertension-related complications.

"Hypertension is a complex disease that affects one in three Americans. It is critical to control hypertension because lowering blood pressure has been shown to reduce the risk of serious health consequences, including stroke and heart attack," said Domenic Sica, M.D., professor of internal medicine and nephrology at Virginia Commonwealth University Medical Center. "The approval of EDARBYCLOR provides an effective treatment option to lower blood pressure for appropriate patients with hypertension who may require a combination of drugs to help achieve blood pressure goals."

Takeda Global Research & Development Center, Inc. U.S. submitted the new drug application for EDARBYCLOR in February 2011. The overall clinical program consisted of five phase 3 clinical studies involving more than 5,000 patients with hypertension. The studies, evaluating the safety and efficacy of EDARBYCLOR, ranged from eight weeks to 52 weeks in duration, with doses of azilsartan medoxomil/chlorthalidone ranging from 20/12.5 to 80/25 mg once daily. The studies demonstrated EDARBYCLOR:

• Lowered mean trough (22-24 hours) systolic blood pressure (SBP) by Ambulatory Blood Pressure Monitoring significantly more than either azilsartan medoxomil or chlorthalidone alone
• Lowered blood pressure in black and non-black patients at similar levels
• Lowered clinic SBP significantly more than the fixed-dose combination of olmesartan medoxomil-hydrochlorothiazide at its highest approved dose (40/25 mg doses for both medications)

The most common adverse reactions seen in clinical studies were dizziness and fatigue.

"In clinical studies, EDARBYCLOR demonstrated statistically significant blood pressure reductions compared to its respective monotherapies and was shown to be superior to the fixed-dose combination of olmesartan medoxomil and hydrochlorothiazide at maximum respective doses," said Paulos Berhanu, M.D., executive medical director of medical & scientific affairs at Takeda. "It is our belief this innovative treatment helps reinforce Takeda's family of cardiovascular therapies by providing a new option to help appropriate patients, regardless of age, gender or race, work toward reaching their blood pressure goals."

About Hypertension
Hypertension, or high blood pressure, is a chronic medical condition in which blood pressure is elevated at 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. Hypertension impacts approximately 75 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 2009.

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 recently received Marketing Authorization in Europe and is currently available in the United States 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 and may be used as an initial therapy if a patient is likely to need multiple drugs to achieve blood pressure control. The recommended starting dose of EDARBYCLOR in adults is 40/12.5 mg taken orally once daily. The maximum recommended 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 fetus.

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. Adverse reactions include 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 can cause symptomatic hypotension. 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 and 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.

EDARBYCLOR attenuates chlorthalidone-associated hypokalemia. Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone. Coadministration of digitalis may exacerbate the adverse effects of hypokalemia.

Hyperuricemia (chlorthalidone) 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 and fatigue. Elevations of creatinine (2 percent) were typically transient, or nonprogressive and reversible, and associated with large blood pressure reductions.

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 increase risk of renal dysfunction and interfere with antihypertensive effect. Renal clearance of lithium is reduced by diuretics, such as chlorthalidone, increasing the risk of lithium toxicity.

For further information:

Please click here for complete EDARBI Prescribing Information or here for complete EDARBYCLOR Prescribing Information.

Indications and Usage
EDARBI and EDARBYCLOR are indicated for the treatment of hypertension to lower blood pressure. EDARBI is an angiotensin II receptor blocker (ARB) and EDARBYCLOR is an ARB and a thiazide-like diuretic combination. EDARBYCLOR may be used if not adequately controlled on monotherapy or as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. There are no controlled trials demonstrating risk reduction with EDARBI or EDARBYCLOR, but trials with chlorthalidone and at least one pharmacologically similar drug to azilsartan medoxomil have demonstrated such benefits.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. EDARBI and EDARBYCLOR may be used with other antihypertensive agents.

Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals North America, 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 www.tpna.com.

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, www.takeda.com.

Contacts
Ashleigh Duchene
GolinHarris
312-729-4428
[email protected]

Josephine Zammuto
Takeda Global Research & Development Center, Inc., U.S.
224-554-2795
[email protected]

Corporate Communications Dept.
Takeda Pharmaceutical Company Limited
+81-3-3278-2037
 

SOURCE Takeda Pharmaceuticals North America, Inc.