Labetalol

Generic Name: Labetalol
Pharmacological Class: Mixed alpha- and beta-adrenergic blocker
Therapeutic Class: Antihypertensive agent
ATC Code: C07AG01
Common Brand Names: Trandate, Normodyne, Presolol
Regulatory Status: Prescription-only medicine (Rx)
Formulations Available:
– Oral tablets (100 mg, 200 mg, 300 mg)
– Intravenous injection (5 mg/mL ampoules or vials)

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Chemical and Pharmacological Characteristics

• Molecular Formula: C19H24N2O3

• Molecular Weight: 328.41 g/mol

• Chirality: Administered as a racemic mixture of four stereoisomers; alpha-blockade is mainly from the (S,R)-isomer, beta-blockade from (R,R)-isomer

• Receptor Affinity:

  • Non-selective β1 and β2 antagonist

  • Selective α1 antagonist

  • No intrinsic sympathomimetic activity (ISA)

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Mechanism of Action

Labetalol reduces blood pressure via combined alpha-1 and non-selective beta blockade:

• Beta-blockade (β1 and β2):

  • ↓ Heart rate

  • ↓ Cardiac output

  • ↓ Renin secretion from kidneys

• Alpha-1 blockade:

  • ↓ Peripheral vascular resistance (vasodilation)

  • Prevents reflex vasoconstriction from beta blockade alone

The net effect is reduced blood pressure without reflex tachycardia, which is a common limitation of pure vasodilators.

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Therapeutic Indications

Approved Indications (Oral and IV):

1. Hypertension (essential and secondary)

   • Monotherapy or in combination

2. Hypertensive emergencies (IV route)

   • Acute aortic dissection

   • Hypertensive encephalopathy

   • Acute intracerebral hemorrhage

3. Pregnancy-induced hypertension / preeclampsia

   • Preferred agent for blood pressure control in pregnancy

4. Post-operative hypertension

   • Short-term IV control after major surgery

5. Hypertension during anesthesia or perioperative care

6. Thyrotoxic crisis with hypertension and tachycardia

   • Adjunctive off-label use

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Dosage and Administration

Oral Formulation (Hypertension):

• Initial dose:

  • 100 mg twice daily

• Titration:

  • Increase by 100–200 mg twice daily every 2–3 days

• Usual maintenance dose:

  • 200–400 mg twice daily

• Maximum daily dose:

  • 2400 mg in divided doses

May be combined with diuretics, calcium channel blockers, or other antihypertensives.

Intravenous Formulation (Hypertensive Emergency):

• IV bolus:

  • 20 mg over 2 minutes

  • Followed by 40–80 mg every 10 minutes as needed

  • Maximum cumulative dose: 300 mg

• IV infusion:

  • Continuous rate of 1–2 mg/min

  • Adjusted according to response

  • Onset: 2–5 minutes

  • Duration: 2–6 hours

Transition to oral therapy once BP is controlled.

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Pharmacokinetics

• Oral bioavailability: ~25% (due to extensive first-pass metabolism)

• Onset of action (oral): 20–120 minutes

• Onset of action (IV): 2–5 minutes

• Half-life: 5.5 hours (can be prolonged in hepatic impairment)

• Protein binding: ~50%

• Metabolism: Hepatic (glucuronidation)

• Excretion: Primarily via urine (~50–60%), and feces

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Contraindications

• Bronchial asthma or severe chronic obstructive pulmonary disease (COPD)

• Second- or third-degree heart block (without pacemaker)

• Overt cardiac failure or cardiogenic shock

• Severe bradycardia (<45 bpm)

• Sick sinus syndrome (without pacemaker)

• Pheochromocytoma (without alpha blockade)

• Hypersensitivity to labetalol or formulation excipients

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Warnings and Precautions

1. Bronchospasm:

   • Non-selective β2 blockade may provoke bronchoconstriction in susceptible individuals

2. Heart failure:

   • May worsen pre-existing heart failure or precipitate decompensation

3. Bradycardia / AV block:

   • Monitor heart rate closely

   • Avoid use with other AV nodal blockers unless clinically justified

4. Orthostatic hypotension:

   • Especially with IV use or high doses

   • Monitor closely in elderly or volume-depleted patients

5. Hepatic impairment:

   • Clearance significantly reduced

   • Monitor liver enzymes; discontinue if hepatotoxicity suspected

6. Diabetes mellitus:

   • May mask hypoglycemia symptoms (e.g., tachycardia)

   • Does not significantly impair glucose metabolism

7. Peripheral vascular disease and Raynaud’s syndrome:

   • May worsen symptoms due to β2 blockade

8. Abrupt withdrawal:

   • Avoid; may precipitate rebound hypertension or angina

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Adverse Effects

Very Common / Common (>1%):

• Orthostatic hypotension

• Dizziness

• Fatigue

• Nausea

• Headache

• Paresthesia

• Ejaculatory failure

• Diarrhea

Uncommon (0.1–1%):

• Hepatotoxicity (including hepatitis)

• Scalp tingling

• Dyspnea

• Nasal congestion

• Palpitations

• Skin rash

• Edema

Rare (<0.1%):

• Bronchospasm

• Heart block

• Exacerbation of angina

• Hepatic necrosis (very rare but potentially fatal)

• Thrombocytopenia

• Depression or mood changes

Liver function abnormalities typically appear within 2–12 weeks of therapy initiation and resolve upon discontinuation.

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Drug Interactions

Interacting Agent	Effect	Clinical Consideration
Calcium channel blockers (verapamil, diltiazem)	Additive bradycardia or AV block	Avoid concomitant IV use; monitor closely
Anesthetic agents	Enhanced hypotension	Monitor BP intraoperatively
Other antihypertensives	Additive hypotension	Adjust doses accordingly
Insulin or oral hypoglycemics	Masks hypoglycemia symptoms	Monitor glucose and educate patients
Cimetidine	↑ Labetalol levels	May require dose adjustment
Tricyclic antidepressants	↓ Antihypertensive effect	Monitor BP

Pregnancy and Lactation

Pregnancy:

• Category C (FDA) / Preferred agent (UK NICE) for severe hypertension in pregnancy

• Widely used for preeclampsia and gestational hypertension

• Does not reduce uteroplacental perfusion significantly, unlike pure beta-blockers

• Appears safe for fetus when used under medical supervision

Lactation:

• Excreted in breast milk in small amounts

• Considered compatible with breastfeeding

• Monitor infant for bradycardia, hypotension, or poor feeding (rare)

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Use in Special Populations

• Elderly: Increased sensitivity to hypotension; start at lower dose

• Hepatic impairment: Clearance reduced; use with caution

• Renal impairment: No dose adjustment needed

• Children: Not commonly used; data limited to special cases

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Monitoring Parameters

• Blood pressure (baseline, during titration, ongoing)

• Heart rate (avoid <60 bpm)

• Liver function tests (especially during the first 12 weeks)

• Signs of orthostatic hypotension (especially with IV use)

• ECG (if AV block or arrhythmias suspected)

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Comparison with Other Antihypertensives

Feature	Labetalol	Atenolol	Amlodipine	Methyldopa	Hydralazine
Beta-blocking	Yes (non-selective)	Yes (β1-selective)	No	No	No
Alpha-blocking	Yes	No	No	No	No
Vasodilation	Moderate	Minimal	High	Yes	High
Use in pregnancy	Preferred	Not preferred	Safe	Safe	Second-line
IV formulation	Yes	No	No	Rarely used	Yes

Patient Counseling Information

• May cause dizziness or fatigue when standing; rise slowly from sitting or lying

• Do not discontinue suddenly; taper gradually under physician supervision

• Report symptoms of wheezing, shortness of breath, slow pulse, or fainting

• Monitor blood pressure regularly

• May interact with diabetes medications – monitor glucose

• Inform anesthesiologist before surgery about labetalol use

• If using IV form, remain supine or seated during infusion to avoid syncope

• Tablets can be taken with or without food, but consistently in the same way

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Storage

• Store oral tablets at controlled room temperature (15–30°C)

• Protect IV solution from light and excessive heat

• Use IV preparation immediately after dilution; discard unused portion