What is the recommended dosing regimen for irbesartan (Angiotensin II Receptor Blocker) in patients with hypertension or diabetic nephropathy?

Irbesartan Dosing

For hypertension, start irbesartan at 150 mg once daily and titrate to 300 mg once daily as needed for blood pressure control; for diabetic nephropathy, use 300 mg once daily as the mandatory target dose for optimal renal protection. 1

Hypertension Dosing

• Initial dose: 150 mg once daily 1
• Maximum dose: 300 mg once daily for blood pressure control 1
• The antihypertensive effect is apparent after the first dose, with near-maximal effect achieved by 2 weeks 1
• Trough effects (24 hours post-dose) after 6-12 weeks show systolic/diastolic reductions of 8-10/5-6 mmHg at 150 mg and 8-12/5-8 mmHg at 300 mg 1
• No further blood pressure reduction occurs at doses exceeding 300 mg 1
• May be administered with or without food 1

Diabetic Nephropathy Dosing

• The recommended dose is 300 mg once daily—this is not negotiable for optimal renal protection 1
• Start at 150 mg once daily and titrate to 300 mg once daily 2
• The 300 mg dose provides maximal renoprotection independent of blood pressure lowering, making it the target even if blood pressure is already controlled 3
• KDIGO guidelines strongly recommend (Grade 1B) titrating to the highest approved dose tolerated in patients with diabetes, hypertension, and albuminuria 3

Evidence Supporting 300 mg for Nephropathy

• The IRMA-2 trial demonstrated a dose-dependent renoprotective effect, with 300 mg daily showing almost 3-fold greater risk reduction in CKD progression compared to lower doses at 2 years—an effect independent of blood pressure 3, 2
• The IDNT trial showed 300 mg daily resulted in a 33% decrease in risk of doubling serum creatinine and a 20% risk reduction in the composite endpoint of doubling serum creatinine, ESRD, or death (p=0.0234) 1
• Irbesartan 300 mg reduced proteinuria by approximately 27% within 3 months and slowed the rate of loss of renal function by 18.2% 1
• In IDNT, 83% of patients received the target 300 mg dose more than 50% of the time 1

Special Populations

• Volume- or salt-depleted patients (including those on vigorous diuretic therapy or hemodialysis): Start at 75 mg once daily 1
• No dosage adjustment required in elderly patients or those with renal or hepatic impairment 4

Monitoring Requirements

• Check serum creatinine and potassium within 2-4 weeks after starting or changing dose 2
• Continue therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 2
• Monitor at least annually thereafter 2

Combination Therapy

• Irbesartan plus hydrochlorothiazide produces additive blood pressure reductions 1
• Adding irbesartan to hydrochlorothiazide 6.25 mg, 12.5 mg, or 25 mg produced further dose-related reductions similar to irbesartan monotherapy 1
• Never combine with ACE inhibitors, other ARBs, or direct renin inhibitors 2

Critical Precautions

• Contraindicated in pregnancy—ensure contraception in women of childbearing potential 2
• Counsel patients to hold irbesartan during intercurrent illness, volume depletion, bowel preparation, or prior to major surgery 5
• The drug is well tolerated with adverse event rates similar to placebo; headache was the most common complaint 4
• Cough incidence is lower than with ACE inhibitors, and ankle edema does not occur 6