rt.
Store at 25°C (77°F); excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room
Temperature].
Protect from moisture and light.
Dispense and store in original container.
Rx Only
Takeda
Distributed by:
Takeda Pharmaceuticals
America, Inc.
Deerfield, IL 60015
C081-01
Manufacturer:
Takeda Pharmaceuticals North America, Inc.
Pharmacological Class:
Angiotensin II receptor blocker (ARB).
Active Ingredient(s):
Azilsartan medoxomil 40mg, 80mg; tabs.
Indication(s):
Hypertension. May be used alone or in combination with other antihypertensive agents.
Pharmacology:
Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II, a pressor agent, by selectively blocking the binding of angiotensin II to the AT1 receptor in tissues such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.
The actual drug substance is the potassium salt of azilsartan medoxomil, also known as azilsartan kamedoxomil. This is hydrolyzed to the active metabolite, azilsartan, in the gastrointestinal tract as it is absorbed. Azilsartan is highly protein-bound to plasma albumin, and it undergoes metabolism by the CYP2C9 enzyme. It is cleared by both renal and hepatic mechanisms. Steady-state levels are attained within 5 days of dosing. There were no observed clinically significant changes in serum potassium or sodium.
Clinical Trials:
The results of seven double-blind, randomized studies, including both placebo-controlled and active comparator-controlled studies ranging from 6 weeks to 6 months in duration, have demonstrated the antihypertensive effects of azilsartan. A total of 5941 patients with mild, moderate, or severe hypertension were involved in the studies. Azilsartan, dosed at 80mg daily, was statistically superior to placebo and active comparators (olmesartan and valsartan) in both clinic (trough measurements) and 24-hour mean blood pressure measurements (ambulatory) in two 6-week studies. In a study comparing azilsartan to valsartan over 24 weeks, similar results were observed. Most of the antihypertensive effect was evident within the first 2 weeks of treatment.
In a study that randomized patients to placebo or continued azilsartan therapy after 26 weeks, azilsartan has demonstrated a sustained and consistent antihypertensive effect during long-term treatment. There was no rebound effect observed after the abrupt cessation of azilsartan treatment. While azilsartan was effective regardless of race, the effect, as monotherapy, in black patients was about half as great as the effect in others. This difference in effectiveness has been observed in other ARBs and in ACE inhibitors as well, and it is attributed to the generally low levels of renin in this population.
Legal Classification:
Rx
Adults:
≥18 years: Monotherapy, not volume-depleted: 80mg once daily. Volume-depleted (eg, concomitant high-dose diuretics): initially 40mg once daily.
Children:
<18 years: not recommended.
Warnings/Precautions:
Correct salt/volume depletion before starting therapy, or reduce initial dose; monitor for hypotension. Severe CHF. Renal artery stenosis. Renal impairment (monitor serum creatinine). Pregnancy (Cat. C in 1st trimester; Cat. D in 2nd and 3rd tri |
