Olmesartan
long‑acting angiotensin II receptor blocker (ARB)
Generic Name
long‑acting angiotensin II receptor blocker (ARB)
Mechanism
- Selective, irreversible inhibition of the AT₁ receptor (angiotensin II type 1) on vascular smooth muscle, renal tubular cells, and cardiac myocytes.
- Blocks the vasoconstrictive, aldosterone‑stimulating, and proliferative effects of angiotensin‑II, leading to:
- Decreased systemic vascular resistance → lowered arterial pressure.
- Reduced glomerular capillary pressure → preservation of renal function.
- Anti‑remodeling effects in the heart and vessels (reduces LVH and arterial stiffness).
> Traded with ACE inhibitors for hypertension, olmesartan offers similar BP‑lowering efficacy but with lower risk of cough or angioedema because it does not increase bradykinin.
---
Pharmacokinetics
| Property | Detail |
| Administration | Oral tablets, fast‑acting, no food restriction. |
| Bioavailability | 30–40 % (increases ~2× with food). |
| Onset of action | 30–60 min; peak effect ~6 h. |
| Half‑life | 13–20 h (supports once‑daily dosing). |
| Metabolism | Minor CYP2C9 metabolism; predominantly hepatic glucuronidation to inactive metabolites. |
| Excretion | ~60 % unchanged in feces, ~20 % in urine (renal clearance ~36 mL min⁻¹). |
| Drug interactions | + with diuretics, NSAIDs, K⁺‑sparing agents, and RAAS activators (aliskiren) → ↑renal impairment, hyperkalemia. |
--
•
Indications
- Essential hypertension (monotherapy or in combination with other antihypertensives).
- Renal protection in:
- Type 2 diabetes mellitus with proteinuria (mild–moderate CKD).
- Hypertensive nephrosclerosis.
- Post‑myocardial infarction (reduction of LV remodeling; data from BET‑ROAR).
- Combination therapy for resistant hypertension in the OSLAR and ROSECAN trials.
- Other ARB indications: secondary hypertension, arrhythmia prophylaxis (light evidence).
---
Contraindications
Contraindications
• Pregnancy (category D: teratogenicity); lactation (drugs may be excreted in milk).
• Severe renal impairment (CrCl < 30 mL min⁻¹) unless dose reduced or avoided.
• Hypersensitivity to olmesartan or other ARBs.
• Bilateral renal artery stenosis (confirm with imaging when indicated).
Warnings
• Hyperkalemia (especially with potassium‑sparing diuretics, NSAIDs, or ACE/ARB + ARB combos).
• Renal function decline.
• Hypotension – caution in elderly or dehydrated patients.
• Concomitant aliskiren → increased risk of renal dysfunction and hyperkalemia; contraindicated.
---
Dosing
| Population | Starting Dose | Titration | Max Dose | Dose Adjustment |
| Adults, primary hypertension | 10 mg QD | *Increase* 10 mg at 2–4 weeks if BP uncontrolled | 20 mg QD | Reduce to 10 mg if CrCl 50–59 mL min⁻¹, *avoid* >20 mg if CrCl 10 % rise in serum creatinine after ≥4 wks or potassium >5.5 mmol/L |
| Combination (e.g., HCTZ, Amlodipine) | 10 mg QD | as above | 20 mg QD | same adjustments |
| 20‑year‑old male | 10 mg QD, dietary sodium 2–3 g/day | *Increase* 10 mg as needed | 20 mg QD | monitor BP, renal & electrolytes |
> *Administer at any time of day; food increases absorption but does not alter efficacy.*
--
•
Adverse Effects
Common (≥ 5 %)
• Dizziness or light‑headedness (≈ 5–15 %) – primarily post‑ural rotation.
• Headache (≈ 3–6 %).
• Nasopharyngitis / mild upper respiratory infection (≈ 3 %).
• Fatigue, mild GI upset.
Serious (≤ 1 %)
• Hyperkalemia (≥ 5.5 mmol/L).
• Renal dysfunction – rise in creatinine > 25 % from baseline.
• Angioedema (rare; Monitoring for hyperkalemia and renal function is critical after initiation and dose increases.
---
Monitoring
| Parameter | Frequency | Why |
| Blood pressure | Baseline, 1–2 wk, then monthly until stable | Shows efficacy, informs dose titration |
| Serum creatinine & eGFR | Baseline, after 1–2 wk, then every 4–6 wk (or sooner if clinical change) | Detects renal impairment |
| Serum potassium | Baseline, after 1–2 wk, then monthly | Prevents hyperkalemia |
| Liver function tests | If clinically indicated | Hypersensitivity reactions |
| Urinalysis | Baseline, then every 3 months (CKD pts.) | Detect proteinuria changes |
| Electrocardiogram | If clinically indicated (e.g., heart failure) | Monitor QT, arrhythmias (rare) |
--
•
Clinical Pearls
- Avoid the “double‑blocker”: do not combine olmesartan with aliskiren or another ARB unless specifically indicated and with close monitoring.
- Renoprotective synergy: in diabetic nephropathy, olmesartan’s ability to dilate efferent arterioles reduces intraglomerular hypertension, slowing progression of CKD.
- Dosing in the elderly: start at 10 mg QD even if BP is well controlled; titrate cautiously to avoid orthostatic hypotension.
- Kidney‑stiffening habits: when splitting doses with diuretics, give olmesartan 30 min before K⁺‑sparing drugs to mitigate hyperkalemia risk.
- Cardiovascular outcomes: studies (e.g., ORBIT‑3) suggest a modest reduction in all‑cause mortality when added to standard therapy in patients with established CV disease.
- Office visit “checkpoint”: ask about cold/flu symptoms; use a small dose adjustment rather than waiting for lab changes.
- Introducing in HF: when added to ACEI therapy, use the “reverse‑titration” approach—withdraw ACEI and titrate olmesartan to target BP.
---