FDA Approves New Combination for Hypertension

Allison Shelley


December 20, 2011

December 20, 2011 — The US Food and Drug Administration today approved azilsartan medoxomil with chlorthalidone (Edarbyclor, Takeda) for the treatment of hypertension. The new combination is the first fixed-dose therapy in the United States to combine an angiotensin II receptor blocker with the diuretic chlorthalidone.

Azilsartan medoxomil, marketed as Edarbi, is already available for the treatment of hypertension in adults. Combining the drug with a diuretic increases its antihypertensive efficacy.

"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," Domenic Sica, MD, from Virginia Commonwealth University Medical Center in Richmond, said in a news release.

The overall clinical program for this new combination with chlorthalidone consisted of 5 clinical trials involving more than 5000 patients with hypertension. The phase 3 studies evaluating the safety and efficacy of the drug ranged from 8 weeks to 52 weeks.

The studies showed the new agent lowered systolic blood pressure significantly more than either azilsartan medoxomil or chlorthalidone alone. The levels as measured by ambulatory blood pressure monitoring were similar across races.

Comparing Olmesartan Medoxomil-Hydrochlorothiazide

Previous studies have shown that azilsartan medoxomil with chlorthalidone lowered systolic blood pressure significantly more than the fixed-dose combination of olmesartan medoxomil-hydrochlorothiazide (Benicar HCT, Daiichi Sankyo) at its highest approved dose of 40/25 mg. The olmesartan combination is marketed under the brand name Olmetec in Europe and Canada.

The new azilsartan medoxomil combination will have a recommended starting dose of 40/12.5 mg with the same maximum dose as the olmesartan medoxomil combination of 40/25 mg. It will be prescribed in a once-daily, single tablet.

The most common adverse reactions are reportedly dizziness and fatigue.

The combination therapy is contraindicated in patients with anuria. Patients with renal impairment should be monitored for worsening renal function.

Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone. Edarbyclor attenuates chlorthalidone-associated hypokalemia. Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone or other thiazide diuretics.

Azilsartan medoxomil with or without chlorthalidone is not recommended during pregnancy. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

The investigators point out that reducing high blood pressure should be part of any comprehensive cardiovascular risk management strategy, which should also include lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limiting sodium intake.

Some patients will require more than 1 drug to achieve blood pressure goals. This new combination may be used with other antihypertensives.