Usage
Labetalol is prescribed for the management of hypertension (high blood pressure), including hypertensive emergencies and hypertension in pregnancy. It’s also used to treat angina pectoris (chest pain). Its pharmacological classification is a combined alpha- and beta-adrenergic blocker (specifically, a nonselective beta-blocker and a selective alpha1-blocker). Labetalol lowers blood pressure by blocking alpha1-adrenergic receptors in peripheral arterioles (reducing peripheral vascular resistance) and beta-adrenergic receptors in the heart (reducing heart rate and cardiac output).
Alternate Names
Labetalol hydrochloride. Brand names include Trandate, Normodyne.
How It Works
Pharmacodynamics: Labetalol blocks both alpha1- and beta-adrenergic receptors. The alpha1-blockade leads to vasodilation, reducing peripheral resistance. Beta1-blockade decreases heart rate and myocardial contractility, lowering cardiac output. The combined effect results in a decrease in blood pressure.
Pharmacokinetics: Labetalol is well-absorbed orally, but undergoes significant first-pass metabolism, resulting in about 25% bioavailability. It’s metabolized in the liver, primarily by glucuronidation. Excretion is mainly through the kidneys (55-60% as metabolites), with the rest in feces. Half-life is 5 to 8 hours.
Mode of Action: Labetalol competitively binds to alpha1-adrenergic receptors in vascular smooth muscle, inhibiting the binding of norepinephrine and preventing vasoconstriction. It also competitively binds to beta1-adrenergic receptors in the heart, inhibiting the effects of catecholamines, which reduces heart rate and contractility.
Elimination Pathways: Primarily renal excretion of metabolites, some fecal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 100 mg orally twice daily. The dose can be increased by 100 mg twice daily every 2-3 days or weekly, depending on response. Usual maintenance dosage is 200-400 mg twice daily. Maximum dose: 2400 mg/day divided into 2 or 3 doses.
- Hypertensive emergency: 20 mg IV over 2 minutes, followed by 40-80 mg every 10 minutes as needed. Maximum IV dose: 300 mg. Alternatively, 1-2 mg/min continuous IV infusion up to a total dose of 300 mg.
Children:
Labetalol use in children is off-label. Dosage must be determined by the doctor, typically starting at 1-3 mg/kg/day divided twice daily, not to exceed 1200 mg/day. Alternatively, 0.3-1 mg/kg intermittent IV bolus. Pediatric safety and efficacy are not fully established. For hypertensive emergency 0.4-1 mg/kg/hr by continuous IV infusion; not to exceed 3 mg/kg/hr.
Special Cases:
- Elderly Patients: Initiate with a lower dose (e.g., 50 mg twice daily) due to potential for reduced clearance. Titrate cautiously.
- Patients with Renal Impairment: No dose adjustment is generally recommended, but cautious titration is advised.
- Patients with Hepatic Dysfunction: Dose reduction may be necessary due to reduced metabolism.
- Patients with Comorbid Conditions: Use cautiously in patients with asthma, diabetes, or heart failure. Monitor closely for worsening of these conditions.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use: Labetalol may be used intravenously in these settings for blood pressure control, titrated to effect. Refer to guidelines for dosage in hypertensive emergencies.
- Emergency Situations (e.g., hypertensive crisis): See dosage for hypertensive emergencies above.
Dosage Adjustments:
Dose adjustments may be necessary in elderly patients, those with hepatic impairment, and those taking interacting medications. Close monitoring is essential.
Side Effects
Common Side Effects:
Dizziness, lightheadedness, fatigue, nausea, scalp tingling, stuffy nose.
Rare but Serious Side Effects:
Bradycardia, hypotension, heart failure, bronchospasm, liver damage, severe allergic reactions.
Long-Term Effects:
Chronic complications from prolonged use are rare, but may include worsening of pre-existing heart failure or bronchospastic disease.
Adverse Drug Reactions (ADR):
Severe hypotension, bradycardia, bronchospasm, heart failure exacerbation, liver injury.
Contraindications
- Asthma or chronic obstructive pulmonary disease
- Cardiogenic shock
- Severe bradycardia or heart block (greater than first degree)
- Severe hypotension
- Decompensated heart failure
Drug Interactions
- Other Antihypertensives: Additive hypotensive effects
- Calcium Channel Blockers (e.g., verapamil, diltiazem): May cause bradycardia and hypotension.
- Beta-Blockers (e.g., atenolol, metoprolol): Additive effects, increased risk of bradycardia and hypotension.
- Tricyclic Antidepressants: May reduce antihypertensive effect of labetalol.
- CYP450 Inhibitors/Inducers: Certain drugs that inhibit or induce CYP450 enzymes (e.g., cimetidine, rifampin) can affect labetalol metabolism.
- Halothane: Synergistic hypotensive effect.
Pregnancy and Breastfeeding
Labetalol is often preferred for treating hypertension during pregnancy. Small amounts are excreted in breast milk, but it’s generally considered safe during breastfeeding. However, monitor the infant for potential bradycardia.
Drug Profile Summary
- Mechanism of Action: Combined alpha1- and beta-adrenergic blockade, leading to vasodilation and reduced cardiac output.
- Side Effects: Dizziness, lightheadedness, fatigue, nausea, bradycardia, hypotension.
- Contraindications: Asthma, cardiogenic shock, severe bradycardia, heart block, severe hypotension.
- Drug Interactions: Other antihypertensives, calcium channel blockers, tricyclic antidepressants, halothane.
- Pregnancy & Breastfeeding: Generally safe during pregnancy and breastfeeding, monitor infant for bradycardia.
- Dosage: Initial 100 mg BID titrated to 200-400 mg BID for hypertension; 20 mg IV bolus followed by 40-80 mg IV q10min for hypertensive emergencies (max 300 mg IV).
- Monitoring Parameters: Blood pressure, heart rate, signs of heart failure, respiratory function.
Popular Combinations
Labetalol is often used in combination with diuretics (e.g., hydrochlorothiazide) for synergistic antihypertensive effects.
Precautions
- General Precautions: Monitor blood pressure and heart rate closely, especially when initiating therapy or adjusting doses.
- Specific Populations: See dosage adjustments for elderly patients and patients with renal or hepatic impairment. Monitor infants of breastfeeding mothers for bradycardia.
- Lifestyle Considerations: Advise patients to avoid alcohol, which can exacerbate hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Labetalol?
A: Initial dose for hypertension is 100 mg twice daily, titrated to 200-400 mg twice daily. Maximum: 2400 mg daily.
Q2: How does Labetalol differ from other beta-blockers?
A: Labetalol blocks both alpha1- and beta-adrenergic receptors, providing a more comprehensive effect on blood pressure.
Q3: Can Labetalol be used in patients with asthma?
A: No, labetalol is contraindicated in patients with asthma due to the risk of bronchospasm.
Q4: What are the common side effects of Labetalol?
A: Common side effects include dizziness, lightheadedness, fatigue, and nausea.
Q5: Can Labetalol be used during pregnancy?
A: Yes, Labetalol is often a preferred choice for hypertension during pregnancy.
Q6: How should Labetalol be administered in hypertensive emergencies?
A: Intravenously, with an initial bolus of 20 mg followed by increments of 40-80 mg every 10 minutes as needed (max 300 mg IV). Alternatively, as a continuous infusion of 1-2 mg/min (max 300 mg).
Q7: Are there any specific monitoring parameters for patients on Labetalol?
A: Closely monitor blood pressure, heart rate, and signs of heart failure or respiratory compromise.
Q8: Does labetalol interact with other medications?
A: Yes, it interacts with other antihypertensives, calcium channel blockers, certain antidepressants and halothane. Concurrent use may require dose adjustment or closer monitoring.
Q9: How does labetalol affect heart rate?
A: Labetalol slows heart rate through its beta1-blocking action. This is part of its mechanism for lowering blood pressure.
