What is the difference between irbesartan (Angiotensin II Receptor Blocker (ARB)) and losartan (Angiotensin II Receptor Blocker (ARB))?

From the Guidelines

Irbesartan and losartan are both effective Angiotensin II Receptor Blockers (ARBs) for treating hypertension and protecting kidney function in diabetic nephropathy, but irbesartan is generally considered more potent and has a longer half-life, allowing for more consistent 24-hour blood pressure control. The main differences between irbesartan and losartan lie in their pharmacokinetic properties.

• Irbesartan has a longer half-life of 11-15 hours, compared to losartan's 2 hours, though its active metabolite lasts 6-9 hours, allowing for once-daily dosing and more consistent blood pressure control 1.
• Irbesartan is more potent, with typical starting doses of 150 mg once daily (maximum 300 mg), while losartan starts at 50 mg daily (maximum 100 mg) 1.
• Irbesartan has higher bioavailability (60-80%) compared to losartan (25-33%) 1.
• Losartan undergoes significant first-pass metabolism in the liver to form an active metabolite (EXP-3174), while irbesartan does not require metabolic activation 1. Both medications are generally well-tolerated with similar side effect profiles, including dizziness, hypotension, and hyperkalemia, and both are contraindicated during pregnancy 1. In terms of clinical outcomes, both irbesartan and losartan have been shown to be effective in reducing the risk of kidney failure and major cardiovascular events in patients with chronic kidney disease (CKD) and diabetes 1. However, a recent network meta-analysis suggested that angiotensin-converting enzyme inhibitors (ACEi) may have a greater benefit in reducing all-cause mortality compared to ARBs, including irbesartan and losartan 1. Overall, the choice between irbesartan and losartan should be based on individual patient factors, such as tolerance, comorbidities, and concomitant medications, as well as consideration of the latest clinical guidelines and evidence-based recommendations 1.

From the FDA Drug Label

Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT1 angiotensin II receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). Losartan potassium is an angiotensin II receptor blocker acting on the AT1 receptor subtype.

The main difference between irbesartan and losartan is their chemical structure and pharmacokinetics.

• Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor.
• Losartan is a non-peptide molecule that acts on the AT1 receptor subtype and has an active metabolite. Both drugs are Angiotensin II Receptor Blockers (ARBs) and work by blocking the effects of angiotensin II on the AT1 receptor, but their exact mechanisms and properties may differ slightly 2 3.

From the Research

Comparison of Irbesartan and Losartan

• Both irbesartan and losartan are Angiotensin II Receptor Blockers (ARBs) used to treat hypertension and other cardiovascular conditions 4, 5.
• The primary difference between the two lies in their pharmacokinetic profiles, including oral bioavailability, potential for food interactions, degree of metabolism, dosing interval, time to peak, volume of distribution, and terminal half-life 6.
• Studies have shown that irbesartan provides a greater and longer-lasting antihypertensive effect compared to losartan 7, 8.
• Irbesartan has been found to be more effective in preventing deterioration of kidney function in patients with diabetic nephropathy, and is considered cost-effective in several countries 4, 6.
• The antihypertensive potency of ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan, based on daily mg dose 5.
• Both irbesartan and losartan are well-tolerated, with a low incidence of adverse effects, but irbesartan has been associated with a lower incidence of adverse events and discontinuations due to adverse events 7, 8.

Efficacy and Safety

• Irbesartan has been shown to be more effective than losartan in reducing trough seated diastolic blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) in patients with mild-to-moderate hypertension 7, 8.
• The 300 mg dose of irbesartan has been found to be associated with the lowest incidence of adverse events and discontinuations due to adverse events 8.
• Both drugs have been found to be well-tolerated, with a similar safety profile 7, 8.

Clinical Implications

• The choice between irbesartan and losartan should be based on individual patient needs and characteristics, as well as the specific clinical context 6.
• Irbesartan may be preferred in patients with diabetic nephropathy or those requiring a more potent antihypertensive effect 4, 6.
• Losartan may be preferred in patients who require a lower dose or have specific concerns about adverse effects 5, 7.