Pronunciation:

(la BET a lole)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

>10%:

Central nervous system: Dizziness (1% to 16%)

Gastrointestinal: Nausea (0% to 19%)

1% to 10%:

Cardiovascular: Edema (0% to 2%), hypotension (1% to 5%); with IV use, hypotension may occur in up to 58%

Central nervous system: Fatigue (1% to 10%), paresthesia (1% to 5%), headache (2%), vertigo (2%)

Dermatologic: Rash (1%), scalp tingling (1% to 5%)

Gastrointestinal: Vomiting (<1% to 3%), dyspepsia (1% to 4%)

Genitourinary: Ejaculatory failure (0% to 5%), impotence (1% to 4%)

Hepatic: Transaminases increased (4%)

Neuromuscular & skeletal: Weakness (1%)

Respiratory: Nasal congestion (1% to 6%), dyspnea (2%)

Miscellaneous: Taste disorder (1%), abnormal vision (1%)

<1% (Limited to important or life-threatening): Hypotension, syncope, bradycardia, heart block, fever, diaphoresis increased, diarrhea, drowsiness, systemic lupus erythematosus, positive ANA, dry eyes, antimitochondrial antibodies, hepatic necrosis, hepatitis, cholestatic jaundice, muscle cramps, toxic myopathy, bronchospasm, Peyronie's disease, alopecia (reversible), micturition difficulty, urinary retention, hypersensitivity, urticaria, angioedema, pruritus, anaphylactoid reaction, Raynaud's syndrome, claudication, CHF, ventricular arrhythmia (I.V.)

Postmarketing and/or case reports: Fever, toxic myopathy, muscle cramps, systemic lupus erythematosus, diabetes insipidus

Other adverse reactions noted with beta-adrenergic blocking agents include mental depression, catatonia, disorientation, short-term memory loss, emotional lability, clouded sensorium, intensification of pre-existing AV block, laryngospasm, respiratory distress, agranulocytosis, thrombocytopenic purpura, nonthrombocytopenic purpura, mesenteric artery thrombosis, and ischemic colitis.

Overdosage/Toxicology:

Drug Interactions:

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

Cimetidine increases the bioavailability of labetalol.

CYP2D6 inhibitors: May increase the levels/effects of labetalol. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Halothane, isoflurane, enflurane (possibly other inhalational anesthetics): Excessive hypotension may occur.

NSAIDs may reduce antihypertensive efficacy of labetalol.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Effects may be decreased by beta-blockers.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers; avoid concurrent I.V. use.

Ethanol/Nutrition/Herb Interactions:

Food: Labetalol serum concentrations may be increased if taken with food.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid natural licorice (causes sodium and water retention and increases potassium loss). Avoid garlic (may have increased antihypertensive effect).

Stability:

Labetalol should be stored at room temperature or under refrigeration and should be protected from light and freezing; the solution is clear to slightly yellow

Stability of parenteral admixture at room temperature (25°C) and refrigeration temperature (4°C): 3 days

Standard diluent: 500 mg/250 mL D5W

Minimum volume: 250 mL D5W

Incompatible with sodium bicarbonate, most stable at pH of 2-4; incompatible with alkaline solutions

Compatibility:

Y-site administration: Compatible: Amikacin, aminophylline, amiodarone, ampicillin, butorphanol, calcium gluconate, cefazolin, ceftazidime, ceftizoxime, chloramphenicol, cimetidine, clindamycin, diltiazem, dobutamine, dopamine, enalaprilat, epinephrine, erythromycin lactobionate, esmolol, famotidine, fentanyl, gatifloxacin, gentamicin, hydromorphone, lidocaine, linezolid, lorazepam, magnesium sulfate, meperidine, metronidazole, midazolam, milrinone, morphine, nicardipine, nitroglycerin, norepinephrine, oxacillin, penicillin G potassium, piperacillin, potassium chloride, potassium phosphates, propofol, ranitidine, sodium acetate, sodium nitroprusside, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vecuronium. Incompatible: Amphotericin B cholesteryl sulfate complex, cefoperazone, ceftriaxone, nafcillin, thiopental, warfarin. Variable (consult detailed reference): Furosemide, heparin, insulin (regular)

Compatibility when admixed: Incompatible: Sodium bicarbonate

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: Oral: 20 minutes to 2 hours; I.V.: 2-5 minutes

Peak effect: Oral: 1-4 hours; I.V.: 5-15 minutes

Duration: Oral: 8-24 hours (dose dependent); I.V.: 2-4 hours

Distribution: Vd: Adults: 3-16 L/kg; mean: <9.4 L/kg; moderately lipid soluble, therefore, can enter CNS; crosses placenta; small amounts enter breast milk

Protein binding: 50%

Metabolism: Hepatic, primarily via glucuronide conjugation; extensive first-pass effect

Bioavailability: Oral: 25%; increased with liver disease, elderly, and concurrent cimetidine

Half-life elimination: Normal renal function: 2.5-8 hours

Excretion: Urine (<5% as unchanged drug)

Clearance: Possibly decreased in neonates/infants

Dosage:

Children:

Oral: Limited information regarding labetalol use in pediatric patients is currently available in literature. Some centers recommend initial oral doses of 4 mg/kg/day in 2 divided doses. Reported oral doses have started at 3 mg/kg/day and 20 mg/kg/day and have increased up to 40 mg/kg/day.

I.V., intermittent bolus doses of 0.3-1 mg/kg/dose have been reported.

For treatment of pediatric hypertensive emergencies, initial continuous infusions of 0.4-1 mg/kg/hour with a maximum of 3 mg/kg/hour have been used. Administration requires the use of an infusion pump.

Adults:

Oral: Initial: 100 mg twice daily, may increase as needed every 2-3 days by 100 mg until desired response is obtained; usual dose: 200-400 mg twice daily; may require up to 2.4 g/day.

Usual dose range (JNC 7): 200-800 mg/day in 2 divided doses

I.V.: 20 mg (0.25 mg/kg for an 80 kg patient) IVP over 2 minutes; may administer 40-80 mg at 10-minute intervals, up to 300 mg total dose.

I.V. infusion: Initial: 2 mg/minute; titrate to response up to 300 mg total dose, if needed. Administration requires the use of an infusion pump.

I.V. infusion (500 mg/250 mL D5W) rates:

1 mg/minute: 30 mL/hour

2 mg/minute: 60 mL/hour

3 mg/minute: 90 mL/hour

4 mg/minute: 120 mL/hour

5 mg/minute: 150 mL/hour

6 mg/minute: 180 mL/hour

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

Dosage adjustment in hepatic impairment: Dosage reduction may be necessary.

Administration:

Monitoring Parameters:

Test Interactions:

Patient Education:

Nursing Implications:

Anesthesia and Critical Care Concerns/Other Considerations:

Dental Health: Effects on Dental Treatment:

Noncardioselective beta-blockers enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Injection, solution, as hydrochloride (Normodyne®): 5 mg/mL (20 mL, 40 mL)

Injection, solution, as hydrochloride [prefilled syringe]: 5 mg/mL (4 mL)

Normodyne®: 5 mg/mL (4 mL, 8 mL)

Tablet, as hydrochloride: 100 mg, 200 mg, 300 mg

Normodyne®: 100 mg, 200 mg, 300 mg

Trandate®: 100 mg, 200 mg [contains sodium benzoate], 300 mg

Extemporaneously Prepared:

Nahata MC and Hipple TF, Pediatric Drug Formulations, 4th ed, Cincinnati, OH: Harvey Whitney Books Co, 2000.

International Brand Names: