General Information

Edarbi (azilsartan medoxomil), a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. It's mechanism of action is to lower blood pressure by inhibiting action of vasopressor hormone Angiotensin II, a polypeptide that causes vasoconstriction, increased blood pressure and aldosterone release.

Edarbi is specifically indicated for the treatment of hypertension, alone or in combination with other antihypertensive agents.

Edarbi is supplied as a tablet for oral administration. The recommended initial dose in adults is 80 mg taken orally once daily.

Edarbyclor is a combination of azilsartan and chlorthalidone, which produces diuresis.

Edarbyclor is specifically indicated for the treatment pf hypertension to lower blood pressure:

• In patients not adequately controlled with monotherapy
• As initial therapy in patients likely to need multiple drugs to help achieve blood pressure goals

Edarbyclor is supplied as a tablet for oral administration. The recommended starting dose of Edarbyclor is 40/12.5 mg taken orally once daily. Most of the antihypertensive effect is apparent within 1 to 2 weeks. The dosage may be increased to 40/25 mg after 2 to 4 weeks as needed to achieve blood pressure goals. Edarbyclor doses above 40/25 mg are probably not useful.

Mechanism of Action

Edarbi, a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzymes (ACE, kinase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.

Edarbyclor also contains chlorthalidone, which produces diuresis with increased excretion of sodium and chloride. The site of action appears to be the cortical diluting segment of the ascending limb of Henle's loop of the nephron. The diuretic effects of chlorthalildone lead to decreased extracellular fluid volume, plasma volume, cardiac output, total exchangeable sodium, glomerular filtration rate, and renal plasma flow. Although the mechanism of action of chlorthalidone and related drugs is not wholly clear, sodium and water depletion appear to provide a basis for its antihypertensive effect.

Side Effects

Adverse events associated with the use of Edarbi may include, but are not limited to, the following:

• diarrhea

Adverse events associated with the use of Edarbyclor may include, but are not limited to, the following:

• dizziness
• fatigue

Clinical Trial Results

The FDA approval of Edarbi was based on seven double-blind, randomized studies. A total of 5,941 subjects with mild, moderate or severe hypertension were studied. The subjects received Edarbi (n=3,672), placebo (n=801) or active comparator (n=1,468). Two 6-week randomized, double blind studies compared the effect on blood pressure of Edarbi at doses of 40 mg and 80 mg, with placebo and with active comparators. Blood pressure reductions compared to placebo were based on clinic blood pressure measurements at trough and 24 hour mean blood pressure by ambulatory blood pressure monitoring (ABPM). Edarbi, 80 mg, was statistically superior to placebo and active comparators for both clinic and 24 hour mean blood pressure measurements. Edarbi also showed a sustained and consistent antihypertensive effect during long-term treatment, as shown in a study that randomized patients to placebo or continued Edarbi after 26 weeks. No rebound effect was observed following the abrupt cessation of Edarbi therapy.

The FDA approval of Edarbyclor was based on the following trials:

A 12-week, randomized, double-blind, forced-titration, active-controlled study in patients (N=1,071) with a mean sitting clinic SBP ≥160 mm Hg and ≤190 mm Hg. There was a 3- to 4-week washout period. Mean ambulatory SBP baselines for each arm were 150.4 mm Hg (Edarbyclor 40/25 mg) and 150.3 mm Hg (Benicar HCT 40/25 mg). The primary endpoint was change from baseline in clinic SBP at week 12. Significantly more patients achieved <140/90 mm Hg with Edarbyclor 40/25 mg vs Benicar HCT at week 12 81.4% of patients taking Edarbyclor 40/25 mg achieved the BP target of <140/90 mm Hg vs 74.6% of patients taking Benicar HCT (olmesartan medoxomil-hydrochlorothiazide) 40/25 mg. Edarbyclor significantly reduced ambulatory systolic BP over 24 hours vs Benicar HCT. Edarbyclor 40/25 mg significantly reduced ambulatory systolic blood pressure (SBP) at each hour of the 24-hour interdosing period in a 12-week study. 

A 12-week, randomized, double-blind, forced-titration, active-controlled study in patients (N=1,071) with a mean sitting clinic SBP of ≥160 mm Hg and ≤190 mm Hg. There was a 3- to 4-week washout period. Mean clinic SBP baselines for each arm were 164.8 mm Hg (Edarbyclor 40/25 mg) and 164.6 mm Hg (Benicar HCT 40/25 mg). The primary endpoint was change from baseline in clinic SBP at week 12. Edarbyclor 40/25 mg lowered clinic SBP by 42.5 mm Hg vs 37.1 mm Hg for Benicar HCT 40/25 mg.

Based on a subgroup analysis of a 12-week, randomized, double-blind, forced-titration, active-controlled study in patients (N=1,071) with a mean sitting clinic SBP of ≥160 mm Hg and ≤190 mm Hg. There was a 3- to 4-week washout period. The primary endpoint was change from baseline in clinic SBP at week 12. Mean clinic SBP baselines for each arm within this subgroup analysis were 166.8 mm Hg (Edarbyclor 40/25 mg) and 165.4 mm Hg (BENICAR HCT 40/25 mg). Edarbyclor 40/25 mg was effective in treating black patients, usually a low-renin population. Edarbyclor 40/25 mg lowered trough SBP in black patients by 31.9 mm Hg vs 26.2 mm Hg for Benicar HCT 40/25 mg, as measured by ambulatory BP.