Once-daily oral therapy for hypertension available
Company: Takeda Pharmaceuticals North America
Pharmacologic class: Angiotensin II receptor blocker (ARB)
Active ingredient: Azilsartan medoxomil 40 mg, 80 mg; tabs.
Indication: 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 five 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 six weeks to six months in duration, have demonstrated the antihypertensive effects of azilsartan. A total of 5,941 patients with mild, moderate, or severe hypertension were involved in the studies. Azilsartan, dosed at 80 mg daily, was statistically superior to placebo and active comparators (olmesartan and valsartan) in both clinic (trough measurements) and 24-hour mean BP measurements (ambulatory) in two six-week studies. In a study comparing azilsartan with valsartan over 24 weeks, similar results were observed. Most of the antihypertensive effect was evident within the first two 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.
Adults: ≥18 years: Monotherapy, not volume-depleted: 80 mg once daily. Volume-depleted (e.g., concomitant high-dose diuretics): initially 40 mg once daily.
Children: <18 years: not recommended.
Warnings/Precautions: Correct salt/volume depletion before starting therapy, or reduce initial dose; monitor for hypotension. Severe congestive heart failure. Renal artery stenosis. Renal impairment (monitor serum creatinine). Pregnancy (Cat. C in first trimester, Cat. D in second and third trimesters: avoid). Nursing mothers: not recommended.
Interactions: May be antagonized by, and renal toxicity potentiated by nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors (monitor renal function periodically in elderly and/or volume-depleted).
Adverse reactions: Diarrhea; rare: orthostatic hypotension, dizziness, nausea, asthenia, fatigue, muscle spasm, cough.
How supplied: Tabs—30, 90 n
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