labetalol hydrochloride
Normodyne, Trandate

Available forms
Available by prescription only
Injection: 5 mg/ml in 20-, 40-, and 60-ml vials and 4- and 8-ml disposable syringes
Tablets: 100 mg, 200 mg, 300 mg

Indications and dosages
 Hypertension, pheochromocytoma. Adults: 100 mg P.O. b.i.d. with or without a diuretic. Dosage may be increased by 100 mg b.i.d. q 2 or 3 days until optimum response is reached. Usual maintenance dosage is 200 to 600 mg b.i.d.; maximum daily dose is 2,400 mg.
Elderly patients: Use a lower maintenance dosage of 100 to 200 mg P.O. b.i.d.
 Severe hypertension and hypertensive emergencies, clonidine withdrawal hypertension ◇. Adults: Initially, 20 to 80 mg I.V. bolus slowly over 2 minutes; may repeat injections of 40 to 80 mg q 10 minutes to maximum dose of 300 mg. Or, give drug as continuous I.V. infusion at 0.5 to 2 mg/minute until satisfactory response is obtained. Usual effective, cumulative dose is 50 to 200 mg, although up to 300 mg may be required.
Oral dose following I.V. therapy: 200 mg P.O. followed by 200 to 400 mg in 6 to 12 hours (depending on blood pressure response); then increase in usual increments at 1-day intervals while patient is hospitalized to achieve desired effects.
 Controlled hypotension during anesthesia ◇. Adults: Initially, 10 to 30 mg I.V. bolus slowly; may repeat injections of 5 to 10 mg I.V., p.r.n.

Pharmacodynamics
Antihypertensive action: Labetalol inhibits catecholamine access to both beta- and postsynaptic alpha-adrenergic receptor sites. Drug also may have a vasodilating effect.

Pharmacokinetics
Absorption: Oral absorption is 90% to 100%; however, drug undergoes extensive first-pass metabolism in the liver and only about 25% of an oral dose reaches systemic circulation unchanged.
Distribution: Distributed widely throughout the body; about 50% protein-bound.
Metabolism: Orally administered drug is metabolized extensively in the liver and possibly in GI mucosa.
Excretion: About 5% of a dose is excreted unchanged in urine; remainder is excreted as metabolites in urine and feces (biliary elimination). Plasma half-life is about 51/2 hours after I.V. administration or 6 to 8 hours after oral administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, patients with severe and prolonged hypotension, patients with a history of obstructive airway disease such as bronchial asthma, and patients with overt cardiac failure, greater than first-degree heart block, cardiogenic shock, or severe bradycardia.
  Use cautiously in patients with heart failure, hepatic failure, chronic bronchitis, emphysema, peripheral vascular disease, and pheochromocytoma.

Interactions
Drug-drug. Beta-adrenergic agonists: May antagonize bronchodilation produced by these drugs. Avoid use together.
Cimetidine: May increase bioavailability of oral labetalol. If used together, labetalol dosage may need adjustment.
Diuretics, other antihypertensives: May potentiate antihypertensive effects of these drugs. Monitor patient closely.
Glutethimide: May decrease bioavailability of oral labetalol. Adjust labetalol dosage as needed.
Halothane: Causes synergistic antihypertensive effect and significant myocardial depression. Monitor patient closely.
Nitroglycerin: Blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. For patients with angina, additional antihypertensive effects may occur. Use cautiously.
Tricyclic antidepressants: May increase risk of labetalol-induced tremor. Avoid use together.

Adverse reactions
CNS: vivid dreams, fatigue, headache, paresthesia, syncope.
CV: orthostatic hypotension, dizziness, ventricular arrhythmias.
EENT: nasal stuffiness.
GI: nausea, vomiting, diarrhea.
GU: sexual dysfunction, urine retention.
Musculoskeletal: muscle spasm, toxic myopathy.
Respiratory: dyspnea, bronchospasm.
Skin: rash, transient scalp tingling.

Effects on lab test results
• May increase transaminase and blood urea levels.

Overdose and treatment
Signs and symptoms of overdose include severe hypotension, bradycardia, heart failure, and bronchospasm.
 After acute ingestion, empty stomach by induced emesis or gastric lavage, and give activated charcoal to reduce absorption. Subsequent treatment is usually symptomatic and supportive.

Special considerations
• For I.V. infusion, dilute labetalol injection to an appropriate concentration (such as 200 mg of drug added to 160 ml of solution to provide a concentration of 1 mg/ml). Administer using a controlled infusion device.
• Don’t mix labetalol with 5% sodium bicarbonate injection because of incompatibility; avoid giving drug in same infusion line with other alkaline solutions (such as furosemide).
• Keep patients receiving I.V. labetalol infusion in the supine position during the infusion and for 3 hours after the infusion.
• Closely monitor blood pressure during and after I.V. infusion; after infusion, monitor blood pressure every 5 minutes for 30 minutes, then at 30-minute intervals for 2 hours, then hourly for 6 hours.
• During direct I.V. infusion, monitor blood pressure before and at 5-minute intervals after each injection; maximum hypotensive effect usually occurs in 5 to 15 minutes after each injection.
• Unlike other beta blockers, labetalol doesn’t decrease resting heart rate or cardiac output.
• Dosage reduction may be needed in patients with hepatic insufficiency and severe renal impairment.
• Dizziness, a troublesome adverse effect, tends to occur in early stages of treatment and in patients taking diuretics or receiving higher doses.
• Ejaculation failure, impotence, and decreased libido have been reported in men.
• Drug may cause a false-positive increase of urine free and total catecholamine levels when measured by a nonspecific trihydroxindole fluorometric method.
• Store tablets and injection at 36° to 86° F (2° to 30° C) and protect from light, moisture, and freezing.
Pregnant patients
• Labetalol has been effective for managing hypertension related to pregnancy and for reduced proteinuria and prevention of eclampsia. Rarely, neonates have had transient hypotension, bradycardia, respiratory depression, and hypoglycemia.
Breast-feeding patients
• Small amounts of drug appear in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established; use drug only if benefits outweigh risk.
Geriatric patients
• These patients may need reduced maintenance dosages because of increased bioavailability or delayed metabolism; they also may experience enhanced adverse effects. Use drug cautiously in elderly patients.

Patient education
• Advise patient that transient scalp tingling may occur at start of therapy but that it usually subsides quickly.
• Tell patient to take drug as prescribed to maintain adequate blood pressure control.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use