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Introduction

  1. Pharmacology. Labetalol is a mixed alpha- and beta-adrenergic antagonist; after intravenous administration, the nonselective beta-antagonist properties are approximately sevenfold greater than the alpha-1 antagonist activity. Hemodynamic effects generally include decreases in heart rate, blood pressure, systemic vascular resistance and possibly atrioventricular conduction velocity. After intravenous injection, peak hypotensive effects occur within 10-15 minutes and persist for 2-4 hours. The drug is eliminated by hepatic metabolism, and has a half-life of 5-6 hours.
  2. Indications. Labetalol may be used to treat hypertension and tachycardia associated with stimulant drug overdoses (eg, cocaine or amphetamines), and clonidine withdrawal. Note: Hypertension with bradycardia suggests excessive alpha1-mediated vasoconstriction, making phentolamine or nitroglycerin preferable. Labetalol could potentially worsen hypertension by reversing beta2-mediated vasodilation or have an unpredictable effect on coronary vascular tone.
  3. Contraindications
    1. Asthma.
    2. Congestive heart failure.
    3. Atrioventricular block.
    4. Known hypersensitivity.
  4. Adverse effects
    1. Paradoxical hypertension may result if used in the presence of stimulants that have strong mixed alpha and beta-adrenergic agonist properties (eg, cocaine, amphetamines) or in patients with pheochromocytoma, owing to labetalol's relatively weak alpha-antagonist properties.
    2. Orthostatic hypotension and negative inotropic effects.
    3. Dyspnea and bronchospasm, particularly in patients with asthma.
    4. Nausea, abdominal pain, diarrhea, tremors, dizziness, and lethargy have been reported.
    5. Labetalol may mask physiologic responses to hypoglycemia (tremor, tachycardia, and glycogenolysis) and, therefore, should be used with caution in patients with diabetes.
    6. Use in pregnancy. FDA Category C (indeterminate). This does not preclude its acute, short-term use for a seriously symptomatic patient (Introduction).
  5. Drug or laboratory interactions
    1. Additive lowering of blood pressure with other antihypertensive agents, halothane, calcium channel antagonists, or nitroglycerin.
    2. Cimetidine increases oral bioavailability.
    3. Forms a precipitate (incompatible) with 5% sodium bicarbonate injection.
    4. Labetalol may cause false-positive elevation of urinary catecholamine levels and can produce a false-positive test for amphetamines on urine drug screening.
  6. Dosage and method of administration
    1. Adult. Give 20 mg by slow IV bolus (over 2 minutes); repeat with 20-80 mg doses every 10 minutes until blood pressure is controlled. Most patients respond to a total dose of 50-200 mg. Alternatively, administer a continuous infusion of 0.5-2 mg/min until blood pressure is controlled. Maximum cumulative dose is 300 mg. After this, give orally 100 mg twice daily.
    2. Children (off-label dosing). Give 0.2-1 mg/kg IV slowly over 2 minutes; repeat every 10 minutes as needed. Alternatively, administer a continuous IV infusion of 0.25-3 mg/kg/hr. Maximum cumulative dose is 40 mg.