Two new molecular entities treat hypertension and COPD

June 15, 2011

FDA has approved azilsartan medoxomil 40-mg and 80-mg tablets for the treatment of hypertension, either alone or in combination with other antihypertensive agents. FDA has also approved roflumilast as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations (not the relief of acute bronchospasm).

Azilsartan medoxomil

(Edarbi, Takeda Pharmaceuticals America)

FDA approved azilsartan medoxomil 40-mg and 80-mg tablets for the treatment of hypertension, either alone or in combination with other antihypertensive agents. A selective AT1 subtype angiotensin II receptor antagonist, azilsartan lowers blood pressure by blocking the action of angiotensin II, a vasopressor hormone that constricts blood vessels.

Efficacy. The antihypertensive efficacy of azilsartan was evaluated in 7 randomized, double-blind trials. Of note, 2 6-week, randomized, double-blind trials compared azilsartan 40 mg and 80 mg to placebo, olmesartan 40 mg, and valsartan 320 mg. Compared to placebo, azilsartan lowered systolic and diastolic blood pressure by up to 15.5 mmHg and 8.6 mmHg, respectively, when measured during clinic visits, and by as much as 14.3 mmHg and 9.4 mmHg, respectively, upon use of 24-hour ambulatory blood pressure monitoring. Most of the antihypertensive effect seen with azilsartan occurred within the first 2 weeks of treatment. When compared to active controls, azilsartan 80 mg daily was found to be statistically superior to the highest FDA-approved doses of olmesartan and valsartan upon both clinic and 24-hour ambulatory blood pressure monitoring.

Safety. Nearly 5,000 patients taking azilsartan (at doses between 20 mg and 80 mg) were evaluated for safety end points during clinical trials. Diarrhea (2%) was the most common adverse effect seen in patients during clinical trials. Other adverse effects (occurring in ≥0.3% of patients and more often than placebo) included: dizziness, cough, asthenia, fatigue, and muscle spasm. As with all approved angiotensin receptor antagonists and other medications that act directly on the renin-angiotensin system, use during pregnancy can result in fetal injury and death and is contraindicated.

Dosing. The recommended dose of azilsartan in adults is 80 mg once daily with or without food. No initial dose adjustment is recommended for elderly patients or patients with mild-to-severe renal impairment, end-stage renal disease, or mild-to-moderate hepatic impairment (not studied in severe hepatic dysfunction). However, prescribers should consider a lower starting dose of 40 mg in patients with volume- or salt depletion, including patients concomitantly treated with higher doses of diuretics.