Avapro (Irbesartan) for Hypertension and Diabetic Nephropathy
Recommended Use and 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 in type 2 diabetes, use 300 mg once daily as the standard dose. 1
Hypertension Management
- Initial dose: 150 mg once daily 1
- Maximum dose: 300 mg once daily for blood pressure control 1
- Volume-depleted patients: Start at 75 mg once daily in patients on vigorous diuretic therapy or hemodialysis 1
- Irbesartan may be administered with or without food and can be combined with other antihypertensive agents 1
Diabetic Nephropathy in Type 2 Diabetes
The recommended dose is 300 mg once daily for renoprotection in patients with type 2 diabetes and nephropathy. 1
Evidence for Nephropathy Treatment
The 300 mg daily dose is supported by landmark trials demonstrating superior renal outcomes:
- IRMA-2 trial (microalbuminuria): Irbesartan 300 mg daily showed a 70% risk reduction in progression to overt nephropathy compared to placebo, with a dose-dependent effect (150 mg showed only 39% reduction) 2, 3
- IDNT trial (macroalbuminuria): Irbesartan 300 mg daily reduced the risk of doubling serum creatinine by 33% versus placebo and 37% versus amlodipine, independent of blood pressure lowering 2, 4
- The renoprotective effects exceed what would be expected from blood pressure reduction alone 2, 3
Patient Selection Criteria
Initiate irbesartan in patients with diabetes, hypertension, and albuminuria, titrating to the highest tolerated dose. 2
Specific Indications:
- Type 2 diabetes with hypertension and microalbuminuria (30-300 mg/g) 2, 3
- Type 2 diabetes with hypertension and macroalbuminuria (>300 mg/g or >900 mg/24h) 2, 4
- Hypertension requiring blood pressure control to <130/80 mmHg in diabetic patients 2
Monitoring Requirements
Check serum creatinine and potassium within 2-4 weeks after starting or changing dose, then monitor at least annually. 5
Key Monitoring Parameters:
- Acceptable creatinine rise: Continue therapy unless serum creatinine increases by >30% within 4 weeks of initiation or dose increase 5
- Potassium monitoring: Essential due to risk of hyperkalemia, particularly in advanced CKD 2
- Albuminuria tracking: Monitor urine albumin excretion to assess treatment response and disease progression 2
Critical Precautions and Contraindications
Absolute Contraindications:
- Pregnancy: Irbesartan is contraindicated; ensure adequate contraception in women of childbearing potential 5
- Bilateral renal artery stenosis: Risk of acute renal failure 6
Combination Therapy Warnings:
Never combine irbesartan with ACE inhibitors, other ARBs, or direct renin inhibitors. 2, 5
- Dual RAS blockade increases risks of hyperkalemia, hypotension, and acute kidney injury without additional benefit 2
- Two clinical trials demonstrated higher adverse event rates with ACE inhibitor plus ARB combinations 2
Temporary Discontinuation Scenarios:
- Interval illness with volume depletion 6
- Planned IV radiocontrast administration 6
- Bowel preparation for colonoscopy 6
- Prior to major surgery 6
Clinical Outcomes and Benefits
Renal Protection:
- Reduces progression from microalbuminuria to macroalbuminuria by 70% at 300 mg dose 2, 3
- Decreases risk of doubling serum creatinine by 33-37% 2, 4
- Reduces proteinuria by 33% on average 4
- Lowers risk of end-stage renal disease by 23% 4
Cardiovascular Considerations:
- While renoprotective, the IDNT trial showed a trend toward higher stroke and non-fatal MI rates with irbesartan versus amlodipine, despite similar blood pressure control 2
- This underscores the importance of comprehensive cardiovascular risk management alongside renal protection 2
Tolerability Profile
Irbesartan is generally well tolerated with an adverse event incidence similar to placebo 2, 7