Nebivolol
Nebivolol
Generic Name
Nebivolol
Mechanism
- Primary: Competitive inhibition of β1‑adrenergic receptors → ↓ heart rate, ↓ cardiac output, ↓ renin release.
- Secondary (vasodilatory):
- Stimulates endothelial NO synthase via β1‑adrenoceptor‑coupled signaling.
- Promotes NO‑dependent smooth‑muscle relaxation → ↓ peripheral resistance.
- Metabolic actions include minor β2‑blocking activity and increased exercise tolerance in some patients.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability ≈ 5 % (first‑pass hepatic metabolism). Peak plasma at 2–3 h. |
| Distribution | High plasma protein binding (~90 %). Volume of distribution ≈ 1.5 L/kg. |
| Metabolism | Primarily via CYP2D6 (CYP2D6 poor metabolizers → ↑ plasma levels). Minor CYP1A2, CYP3A4 involvement. |
| Elimination | Hepatobiliary (≈70 %) and renal (≈20 %). Terminal half‑life ≈ 12 h (β1‑selective component). |
| Drug interactions | Strong inhibitors of CYP2D6 (e.g., fluoxetine) ↑ nebivolol levels; CYP3A4 inducers (e.g., carbamazepine) ↓ levels; concurrent β‑blockers/additive bradycardia. |
Indications
- Essential hypertension (titrated up to 20 mg once daily).
- Heart failure – reduced ejection fraction (HFrEF) as an adjunct to ACEI/ARB and MRA.
- Pre‑operative prophylaxis of postoperative atrial fibrillation (in select trials).
Contraindications
- Contraindications
- Known hypersensitivity to nebivolol or its excipients.
- Severe bradycardia, second‑ or third‑degree heart block (without pacemaker).
- Acute myocardial infarction or decompensated heart failure.
- Warnings
- Heart failure: Monitor for worsening HF; adjust dose if signs progress.
- Hypotension: Initiate at low dose; titrate slowly.
- Beta‑blocker interactions: Avoid simultaneous use with other strong β‑blockers unless clinically justified.
- Pregnancy/Lactation: Category C; avoid unless benefits outweigh risks.
Dosing
- Adults
- Start: 2.5 mg orally once daily (preferably in the morning).
- Titration: Increase by 2.5 mg every 1–2 weeks based on BP response.
- Target: 5–15 mg/day; max 20 mg/day.
- Elderly / CKD – Initiate at low end of range; monitor renal/hepatic parameters.
- Administration tip: Take with water; can be taken with or without food.
Adverse Effects
| Adverse Effect | Frequency / Notes |
| Common (≤10 %) | Fatigue, dizziness, headache, nasopharyngitis, dry mouth, mild bradycardia, mild constipation. |
| Moderate (1–10 %) | Raynaud’s phenomenon, edema, palpitations, dyspnea. |
| Serious (≤1 %) | Severe bradycardia, AV block, hypotension, exacerbation of heart failure, severe asthma exacerbation in susceptible patients. |
| Unique | Rare cases of paradoxical vasoconstriction; monitor for paradoxical tachycardia in the first week. |
Monitoring
- Baseline: BP, heart rate, ECG, renal & liver function tests.
- Follow‑up:
- BP & HR: Week 1–2, then monthly until stable.
- Renal/liver function: Every 3 months or if dose > 10 mg/day.
- ECG: If new symptoms or dose ↑ > 10 mg/day.
- Special populations: More frequent checks in CKD G3‑G5 or hepatic impairment.
Clinical Pearls
- β1‑selectivity + NO‑mediated vasodilation → better tolerability in heart failure than older β‑blockers.
- CYP2D6 poor metabolizers may experience higher plasma concentrations; consider genetic testing or lower starting dose.
- Nebivolol’s once‑daily profile improves adherence over twice‑daily β‑blockers, especially in geriatric cohorts.
- Combination therapy: Nebivolol plus ACEI/ARB offers synergistic BP reduction with minimal additive bradycardia due to its NO effect.
- Perioperative use: In patients undergoing cardiac surgery, nebivolol may reduce postoperative atrial fibrillation incidence when started ≥ 4 weeks pre‑op.
- Rebound hypertension is less common compared to other β‑blockers; abrupt withdrawal can still cause tachycardia and HTN—taper over 1–2 weeks.
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• *References: Standard pharmacology texts (Katzung & Trevor, Goodman & Gilman), FDA prescribing information 2023, and recent meta‑analyses on nebivolol in heart failure.*