Introduction
- 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.
- 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.
- Contraindications
- Asthma.
- Congestive heart failure.
- Atrioventricular block.
- Known hypersensitivity.
- Adverse effects
- 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.
- Orthostatic hypotension and negative inotropic effects.
- Dyspnea and bronchospasm, particularly in patients with asthma.
- Nausea, abdominal pain, diarrhea, tremors, dizziness, and lethargy have been reported.
- Labetalol may mask physiologic responses to hypoglycemia (tremor, tachycardia, and glycogenolysis) and, therefore, should be used with caution in patients with diabetes.
- Use in pregnancy. FDA Category C (indeterminate). This does not preclude its acute, short-term use for a seriously symptomatic patient (Introduction).
- Drug or laboratory interactions
- Additive lowering of blood pressure with other antihypertensive agents, halothane, calcium channel antagonists, or nitroglycerin.
- Cimetidine increases oral bioavailability.
- Forms a precipitate (incompatible) with 5% sodium bicarbonate injection.
- Labetalol may cause false-positive elevation of urinary catecholamine levels and can produce a false-positive test for amphetamines on urine drug screening.
- Dosage and method of administration
- 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.
- 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.