Deerfield, Ill., February 6, 2012 and Osaka, Japan, February 7, 2012 – 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.”
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 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 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 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 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 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.