What is the recommended dosage and use of Azilsartan (angiotensin II receptor antagonist) for treating high blood pressure (hypertension)?

Azilsartan for Hypertension: Dosage and Usage Guidelines

The recommended dosage of azilsartan (Edarbi) for treating hypertension is 80 mg taken once daily, with a starting dose of 40 mg considered for patients treated with high doses of diuretics. 1

Dosing Recommendations

• Azilsartan is an angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension in adults to lower blood pressure and reduce the risk of fatal and nonfatal cardiovascular events 1
• The medication can be administered with or without food and may be used either alone or in combination with other antihypertensive agents 1
• Steady-state levels of azilsartan are achieved within five days, and no accumulation in plasma occurs with repeated once-daily dosing 1
• For patients who are volume or salt-depleted (such as those on high-dose diuretics), consider starting with the lower 40 mg dose to reduce the risk of hypotension 1
• No dosage adjustment is required for patients with mild to severe renal impairment or for elderly patients, though higher serum creatinine values were more likely in patients aged 75 or older 1

Mechanism of Action and Pharmacology

• Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland 1
• The drug has more than 10,000-fold greater affinity for the AT1 receptor than for the AT2 receptor 1
• Azilsartan has tighter and longer-lasting binding to the AT1 receptor compared to other ARBs, which may contribute to its more effective blood pressure reduction 2
• After oral administration, peak plasma concentrations of azilsartan are reached within 1.5 to 3 hours, with an elimination half-life of approximately 11 hours 1
• The estimated absolute bioavailability of azilsartan is approximately 60% 1

Clinical Efficacy

• Studies have shown that azilsartan doses of 40 mg and 80 mg daily reduce blood pressure significantly better than maximal clinical doses of valsartan or olmesartan 2, 3
• At the maximum approved dosage of 80 mg once daily, azilsartan was significantly more effective than maximum dosages of olmesartan (40 mg) or valsartan (320 mg) based on 24-hour ambulatory blood pressure monitoring 3
• When compared to ramipril 10 mg daily, both azilsartan 40 mg and 80 mg resulted in significantly greater reductions in mean systolic blood pressure 4
• The International Society of Hypertension recommends ARBs like azilsartan as part of first-line therapy for hypertension, particularly in specific populations such as those with chronic kidney disease 5

Combination Therapy

• For patients not achieving blood pressure goals on monotherapy, azilsartan can be combined with other antihypertensive agents 1
• The combination of azilsartan with chlorthalidone has shown superior efficacy compared to other sartan-thiazide combinations 6
• When coadministered with amlodipine 5 mg daily, both azilsartan 40 mg and 80 mg decreased systolic blood pressure significantly more than amlodipine alone 4
• In resistant hypertension, azilsartan may be particularly effective as part of a multi-drug regimen due to its potent AT1 receptor blockade 5

Special Populations and Considerations

• For patients with hypertension and chronic kidney disease, ARBs like azilsartan are recommended first-line drugs because they reduce albuminuria in addition to blood pressure control 5
• In patients with hypertension and coronary artery disease, RAS blockers like azilsartan are recommended as first-line therapy, with a target blood pressure of <130/80 mmHg (<140/80 in elderly patients) 5
• For patients with hypertension and heart failure, ARBs are effective in improving clinical outcomes, with a target blood pressure of <130/80 mmHg but >120/70 mmHg 5
• Caution should be exercised when using azilsartan in patients with an activated renin-angiotensin system (e.g., volume or salt depletion), as excessive hypotension may occur 1

Safety and Adverse Effects

• Azilsartan is generally well-tolerated with a safety profile similar to other ARBs 3
• The most common adverse events reported include diarrhea (2%), dizziness, and headache 1, 4
• When pregnancy is detected, azilsartan should be discontinued as soon as possible due to potential fetal toxicity 1
• Dual inhibition of the renin-angiotensin system (e.g., combining azilsartan with ACE inhibitors or aliskiren) is not recommended due to increased risk of renal impairment, hypotension, and hyperkalemia 1
• Monitor for worsening renal function in patients with renal impairment 1

Common Pitfalls and Caveats

• Underdosing is common in clinical practice, with many physicians using lower doses of ARBs than those proven effective in clinical trials 7
• Azilsartan should not be coadministered with aliskiren-containing products in patients with diabetes 1
• Monitor serum lithium levels in patients receiving azilsartan and lithium, as increases in serum lithium concentrations and lithium toxicity have been reported 1
• Correct volume or salt depletion prior to administration of azilsartan to reduce the risk of symptomatic hypotension 1
• Breastfeeding is not recommended during treatment with azilsartan 1