Irbesartan
Irbesartan
Generic Name
Irbesartan
Brand Names
[Atenol]) is a second‑generation angiotensin‑II receptor blocker (ARB) indicated primarily for the management of hypertension and renal protection in diabetic patients.
Mechanism
Irbesartan selectively blocks the binding of angiotensin‑II to the AT1 receptor on vascular smooth muscle and adrenal zona glomerulosa cells, leading to:
• Vasodilation through diminished intracellular Ca²⁺ influx.
• Reduced aldosterone secretion, lowering sodium and water retention.
• Lower systemic vascular resistance and decreased renal efferent arteriole constriction, preserving glomerular filtration.
• Attenuated cell‑proliferative and fibrotic signaling via inhibition of AT1‑mediated MAPK/ERK pathways (beneficial in diabetic nephropathy).
The blockade is reversible and dose‑dependent, with no significant affinity for AT2 receptors.
Pharmacokinetics
| Parameter | Key Points | Notes |
| Absorption | ~70 % oral bioavailability | Absorption enhanced on empty stomach; food may delay Tmax by ~1 h. |
| Distribution | Plasma protein binding ~95 % (primarily albumin). | Volume of distribution ~55 L. |
| Metabolism | Minor hepatic metabolism; major pathway is unchanged excretion. | CYP3A4 may competitively bind but not involved in biotransformation. |
| Elimination | Primarily renal (≈90 %) via glomerular filtration, tubular secretion, and reabsorption. | Half‑life ~12 h (load‑dose ~7 h); steady state reached within 3 days. |
| Special Populations | Dose adjustment in severe renal impairment (CrCl 15‑30 mL/min). | No adjustments required for mild‑moderate hepatic disease. |
Indications
- Hypertension – used alone or in combination with diuretics, calcium‑channel blockers, or β‑blockers.
- Diabetic Nephropathy – in patients with type 2 diabetes and microalbuminuria to slow CKD progression (Class I recommendation).
- Heart Failure – as add‑on to ACEI or ARB therapy in select patients (Class IIa).
- Salt Restriction – tolerable in patients requiring low‑salt diets.
Contraindications
- Pregnancy – Category X: embryotoxicity in animals; contraindicated anytime during pregnancy.
- Severe Renal or Hepatic Impairment – CrCl <30 mL/min or significant hepatic dysfunction.
- Angioedema – prior angiotensin‑II‑receptor blocker or ACE inhibitor induced angioedema.
- Hypersensitivity to irbesartan or other ARBs.
Warnings
• Hyperkalemia – caution when co‑prescribed with potassium‑sparing diuretics, potassium supplements, or ACEI/ARB combination.
• Renal function decline – particularly in volume‑depleted states, post‑prandial HTN, or severe dehydration.
• Hyponatremia – monitor electrolytes in older adults.
Dosing
| Condition | Starting Dose | Titration | Max Daily Dose | Form |
| Hypertension | 150 mg once daily | ↑ 150 mg every 2–4 weeks to 300/450/600 mg | 600 mg | Tablets (150, 300, 450, 600 mg) |
| Diabetic Nephropathy | 150 mg once daily | Titrate to 300 mg if tolerated | 600 mg | Tablets (150, 300, 450, 600 mg) |
| Heart Failure | 150 mg once daily | Increment by 150 mg every 2–4 weeks | 450 mg | Tablets (150, 300, 450 mg) |
• Administration: Take with or without food; never split tablets.
• Missed Dose: Take at next scheduled time; do not double dose.
• Renal Dose Reduction: Not required until CrCl <30 mL/min, then reduce dose by half.
• Elderly: Start at lower end of dosing range.
Adverse Effects
Common (≤10 %)
• Dizziness (hypotension).
• Headache.
• Hyperkalemia (serum K >5.5 mmol/L).
• GI upset (nausea, flatulence).
• Fatigue.
Serious (≤1 %)
• Severe hyperkalemia (>6.5 mmol/L).
• Acute kidney injury or sudden worsening of chronic kidney disease.
• Angioedema (rare).
• Severe hypotension.
Other Rare – peripheral edema, cough (rare for ARBs), allergic reactions.
Monitoring
| Parameter | Frequency | Target / Alert |
| Blood pressure | Weekly for first month, then monthly | ↓≥20 mmHg systolic or 10 mmHg diastolic or >140/90 mmHg |
| Serum potassium | Every 2 weeks after initiation, then every 4 weeks | K >5.5 mmol/L → hold dose |
| Serum creatinine & BUN | Every 2 weeks initially, then monthly | ↑≥30 % from baseline → assess volume status |
| Urine albumin‑to‑creatinine ratio | Every 6 months in diabetic nephropathy | ↑ ≥30 % from baseline → consider dose adjustment |
| Pregnancy test (female of reproductive potential) | Prior to initiation, then as clinically indicated | Positive → discontinue |
Clinical Pearls
- ARB‑ACEi “switch” strategy – If an ACE inhibitor is discontinued for cough or angioedema, switch to irbesartan rather than restarting ACEI to preserve renoprotective benefit.
- Combination with amlodipine – Provides synergistic BP lowering with minimal additive potassium increase; add‑on therapy is Class IIa for resistant HTN.
- Hyperkalemia risk – Concomitant use with potassium‑sparing diuretics or potassium supplements necessitates dosing every other day in high‑risk patients.
- Renal protection window – Early initiation in type 2 diabetic patients with microalbuminuria (within 2 years of diagnosis) offers the greatest benefit in slowing CKD progression.
- Contraindication in pregnancy – A single inadvertent dose in a lactating mother will be excreted excreted; however, low systemic exposure mitigates fetal risk.
- Drug–Drug Interactions – Concomitant statins (e.g., atorvastatin) can modestly increase irbesartan levels; monitor for rhabdomyolysis symptoms.
- Non‑classic ARB side‑effect profile – Irbesartan lacks the cough seen in some ARBs, making it a favorable option for patients with a history of drug‑induced cough.
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• Key Takeaway: *Irbesartan* offers potent AT1 receptor blockade with favorable pharmacokinetics and a robust renal protective effect, making it a cornerstone drug for hypertension and diabetic nephropathy when tailored dosing and vigilant monitoring are employed.