Labetalol Hydrochloride

Pronunciation: (la-BAYT-a-lol HYE-droe-KLOR-ide)
Class: Alpha-adrenergic blocker, Beta-adrenergic blocker

Trade Names

Labetalol Hydrochloride
- Injection 5 mg/mL

Trandate
- Tablets 100 mg
- Tablets 200 mg
- Tablets 300 mg

Apo-Labetalol (Canada)

Pharmacology

Selectively blocks alpha-1 receptors and nonselectively blocks beta receptors to decrease BP, heart rate, and myocardial oxygen demand.

Pharmacokinetics

Absorption

Completely absorbed from the GI tract. T _max is 1 to 2 h. Relative bioavailability is 100% (oral and IV). Absolute bioavailability for oral compared with IV is 25%. Absolute bioavailability increases when administered with food. Steady-state levels are reached by approximately the third day of dosing.

Distribution

Crosses the placental barrier. Approximately 50% protein bound.

Metabolism

Mainly through conjugation to glucuronide metabolites.

Elimination

Plasma half-life is 6 to 8 h (not altered in patients with decreased hepatic or renal function). Metabolites excreted in urine and via the bile into the feces. Approximately 55% to 60% appears in urine as conjugates or unchanged labetalol within 24 h. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the general circulation.

Peak

2 to 4 h.

Duration

Lasting at least 8 h following single oral dose of 100 mg and more than 12 h after a 300 mg dose.

Special Populations

Elderly

Elimination is reduced; lower maintenance dosage is generally required in elderly patients.

Indications and Usage

Management of hypertension.

Unlabeled Uses

Treatment of pheochromocytoma; management of clonidine-withdrawal hypertension.

Contraindications

Bronchial asthma; overt cardiac failure; greater than first-degree heart block; cardiogenic shock; severe bradycardia; conditions associated with severe and prolonged hypotension; history of obstructive airway disease, including asthma; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO Start with 100 mg twice daily. After 2 or 3 days, using standing BP as an indicator, the dosage may be titrated in increments of 100 mg twice daily every 2 or 3 days. Usual maintenance dosage is 200 to 400 mg twice daily. IV 20 mg over 2 min; then 40 or 80 mg every 10 min up to max of 300 mg. Infusions of 2 mg/min can be initiated and titrated to response.

General Advice

• Tablets
• Administer with food; tablets can be crushed.
• If nausea and dizziness occur with twice-daily dosing of oral form, same total daily dose can be administered as divided doses 3 times daily.

• Injection
• Keep patient supine during IV administration and for 3 h afterward.
• Labetalol is compatible with following parenteral solutions: Ringer's, lactated Ringer's, dextrose 5% and Ringer's, lactated Ringer's 5% and dextrose 5%, dextrose 5%, sodium chloride 0.9%, dextrose 5% and sodium chloride 0.2%, dextrose 2.5% and sodium chloride 0.45%, dextrose 5% and sodium chloride 0.9%, and dextrose 5% and sodium chloride 0.33%.
• Do not freeze injection vials. Protect from light. Parenteral solution is stable for 24 h after dilution.

Storage/Stability

Store tablets between 36° and 86°F. Protect from excessive moisture. Store injection between 36° and 86°F. After dilution, the parenteral solution is stable for 24 h refrigerated or at room temperature. Protect from freezing. Protect from light.

Drug Interactions

Beta-adrenergic agonists

Blunted bronchodilator effect.

Cimetidine

Increased bioavailability of labetalol.

Digitalis

Concomitant use may increase the risk of bradycardia.

Diuretics

Additive antihypertensive effect may occur. When used therapeutically, be prepared to adjust the labetalol dosage as needed.

Inhalation anesthetics

May exaggerate hypotension.

Nitroglycerin

Increased hypotension.

Tricyclic antidepressants

Bioavailability may be increased, increasing the adverse effects.

Incompatibility

Injection not compatible with sodium bicarbonate 5%.

Laboratory Test Interactions

False-positive tests for urinary amphetamines; false-positive increases in levels of urinary catecholamines, metanephrine, normetanephrine, and vanillymandelic acid.

Adverse Reactions

Cardiovascular

Edema, postural hypotension (1%); bradycardia, heart block, hypotension, syncope.

CNS

Dizziness (16%); fatigue (10%); paresthesia often described as scalp tingling (5%); headache (2%); asthenia (1%).

Dermatologic

Rash (1%); alopecia, bullous lichen planus, facial erythema, generalized maculopapular rash, lichenoid rash, Peyronie disease, pruritus, psoriasiform rash, urticaria.

EENT

Nasal stuffiness (6%); vertigo (2%); abnormal vision (1%); dry eyes.

GI

Nausea (19%); dyspepsia (4%); vomiting (3%); taste distortion (1%).

Genitourinary

Ejaculation failure (5%); impotence (4%); difficulty in micturition including urinary bladder retention.

Hepatic

Cholestatic jaundice, elevated liver function tests, hepatic necrosis, hepatitis.

Hypersensitivity

Anaphylactoid reactions, angioedema.

Lab Tests

Reversible increases in serum transaminases (4%).

Musculoskeletal

Muscle cramps, toxic myopathy.

Respiratory

Dyspnea (2%); bronchospasm.

Miscellaneous

Edema (2%); antimitochondrial antibodies, fever, positive antinuclear factor, SLE.

Precautions

Monitor Monitor BP to determine response to parenterally administered labetalol.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hepatic Function

Use with caution because drug metabolism may be impaired.

Special Risk Patients

Use with caution in patients with diabetes mellitus, CHF, respiratory difficulties, or severely elevated BP, or with nonallergic bronchospasm (eg, chronic bronchitis, emphysema).

Cardiac failure

Cardiac failure has been observed in patients with or without history.

Diabetes mellitus and hypoglycemia

Labetalol may prevent the appearance of premonitory signs and symptoms (eg, tachycardia) of acute hypoglycemia.

Hepatic injury

Rarely, severe hepatocellular injury may occur.

Major surgery

Protracted severe hypotension and difficulty in restarting or maintaining a heartbeat has been reported with beta-blockers.

Pheochromocytoma

Use with caution in patients with pheochromocytoma because paradoxical hypertension may occur in some patients.

Withdrawal

Do not discontinue abruptly. Abrupt discontinuation may worsen angina and precipitate ischemic event in susceptible patients.

Overdosage

Symptoms

Bronchospasm, cardiac failure, excessive bradycardia, excessive orthostatic hypotension, seizures.

Patient Information

• Caution patient to avoid sudden position changes to prevent orthostatic hypotension. Advise use of support hose.
• Advise patient to notify dentist and other health care providers of drug therapy before treatment or surgery.
• Caution diabetic patient to monitor serum glucose carefully.
• Instruct patient to not discontinue drug abruptly.
• Advise patient to carry medical identification (eg, card, bracelet) indicating medical condition and drug regimen.
• Instruct patient how to measure BP and pulse.
• Emphasize importance of the following other modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
• Inform patient that transient scalp tingling may occur, especially when treatment is initiated.
• Instruct patient to report the following symptoms to health care provider: confusion, dizziness, fatigue, fever or depression, shortness of breath, slow heart rate, swelling of ankles and feet.
• Advise patient that drug causes dizziness and to use caution while driving or performing other tasks requiring mental alertness.

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