What is the recommended dosing for Ibesartan (Angiotensin II receptor antagonist) in patients with hypertension and diabetic nephropathy?

Irbesartan Dosing for Hypertension and Diabetic Nephropathy

For patients with hypertension and diabetic nephropathy, irbesartan should be dosed at 300 mg once daily to achieve optimal renoprotective effects, with titration starting at 150 mg once daily if needed. 1, 2

Initial Dosing Algorithm

• Standard starting dose: 150 mg once daily for hypertension 1
• Maximum dose: 300 mg once daily 1
• Diabetic nephropathy: 300 mg once daily (recommended fixed dose) 1, 2
• Volume/salt-depleted patients: 75 mg once daily (including patients on vigorous diuretic therapy or hemodialysis) 1

Specific Dosing Based on Clinical Presentation

For Hypertension with Diabetic Nephropathy:

• Patients with albuminuria (≥30 mg/g creatinine): Start with 150 mg once daily and titrate to 300 mg once daily 2
• Patients with overt nephropathy (≥300 mg/g creatinine): Use 300 mg once daily 2, 1

Dosing Considerations:

• Blood pressure targets: Aim for <130/80 mmHg in most patients with diabetes and hypertension 2
• Severe hypertension (≥160/100 mmHg): Consider combining irbesartan with another agent (thiazide-like diuretic or dihydropyridine calcium channel blocker) 2, 3
• Administration: Can be taken with or without food 1

Evidence Supporting 300 mg Dosing for Nephropathy

• The IRMA-2 study demonstrated a dose-dependent reduction in progression of CKD with irbesartan, showing almost 3-fold risk reduction with 300 mg daily compared to lower doses 2, 4
• At 300 mg daily, irbesartan reduced the risk of developing overt nephropathy by 70% versus placebo in patients with microalbuminuria 5
• In the IDNT trial, irbesartan 300 mg daily decreased the risk of doubling serum creatinine by 33% compared to placebo and 37% compared to amlodipine 6
• The renoprotective effect of irbesartan is independent of its blood pressure-lowering properties 2, 4, 6

Monitoring and Titration

• Initial monitoring: Check serum creatinine and potassium within 2-4 weeks after starting or changing dose 2
• Ongoing monitoring: Check serum creatinine/eGFR and potassium at least annually 2
• Dose adjustment: Continue therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 2

Important Precautions

• Pregnancy: Contraindicated during pregnancy; advise contraception in women receiving irbesartan 2
• Hyperkalemia management: Often can be managed by measures to reduce serum potassium rather than immediately stopping the medication 2
• Combination therapy: Never combine irbesartan with ACE inhibitors, other ARBs, or direct renin inhibitors 2, 3
• Volume depletion: Consider reduced starting dose (75 mg) in patients with intravascular volume depletion 1

Clinical Pearls

• Irbesartan provides 24-hour blood pressure control with once-daily dosing 7
• The renoprotective effects of irbesartan at 300 mg daily extend to both early nephropathy (microalbuminuria) and late nephropathy (overt proteinuria) 5
• Optimal systolic blood pressure target for renoprotection appears to be between 120-130 mmHg 8
• Irbesartan is generally well-tolerated with an adverse event profile similar to placebo 7