What is the maximum recommended dose of irbesartan for any indication?

Maximum Dose of Irbesartan

The maximum recommended dose of irbesartan is 300 mg once daily for both hypertension and diabetic nephropathy. 1

FDA-Approved Dosing

• For hypertension, the FDA-approved starting dose is 150 mg once daily, which can be increased to a maximum of 300 mg once daily as needed to control blood pressure. 1
• For nephropathy in type 2 diabetic patients, the recommended dose is 300 mg once daily. 1
• In patients with volume or salt depletion (e.g., those on vigorous diuretic therapy or hemodialysis), the initial dose should be reduced to 75 mg once daily. 1

Clinical Evidence Supporting Maximum Dose

• The Irbesartan Diabetic Nephropathy Trial (IDNT) demonstrated that the highest irbesartan dose (300 mg daily) reduced the risk of chronic kidney disease progression by approximately three-fold compared with lower doses, showing a clear dose-dependent benefit. 2
• Irbesartan 300 mg daily lowered the risk of doubling serum creatinine by 33% independent of blood pressure control, indicating direct renoprotective effects at this maximum dose. 2
• Clinical trials in hypertensive patients with chronic renal insufficiency used irbesartan 150 mg titrated to 300 mg once daily, demonstrating effective blood pressure control and good tolerability at the maximum dose. 3

Renal Impairment Considerations

• No dose adjustment is necessary in patients with mild to severe renal impairment, including those on maintenance hemodialysis, as pharmacokinetic studies showed no significant relationship between creatinine clearance and irbesartan exposure. 4
• Irbesartan is not cleared by hemodialysis, so the 300 mg maximum dose remains appropriate for dialysis patients. 4
• The KDIGO 2020 guideline recommends titrating ARBs like irbesartan to the maximum tolerated dose to achieve optimal renal protection in chronic kidney disease. 2

Important Safety Considerations

• Irbesartan can be administered with or without food, and food does not affect its bioavailability (60-80%). 5
• The drug is well tolerated at the maximum 300 mg dose, with adverse event rates similar to placebo in clinical trials. 6, 5
• Hyperkalemia requiring discontinuation occurred in only one patient across studies of irbesartan 150-300 mg in patients with chronic renal disease. 3
• In elderly patients (≥65 years), no dosage adjustment is required, and irbesartan 150-300 mg has been shown to be effective and well tolerated. 7

Common Pitfall to Avoid

• Do not exceed 300 mg daily; there is no evidence supporting higher doses, and the FDA label explicitly states 300 mg as the maximum. 1
• Ensure volume status is adequate before initiating therapy, particularly at higher doses, to avoid exaggerated hypotensive responses. 1, 4