No

Alpha-/Beta- Blocker

Treatment of mild to severe hypertension; I.V. for hypertensive emergencies

C (per manufacturer); D (if used in 2nd and 3rd trimesters, based on expert analysis)

Clinical effects on the fetus: Crosses the placenta. Bradycardia, hypotension, hypoglycemia, intrauterine growth rate (IUGR). IUGR probably related to maternal hypertension. Available evidence suggests safe use during pregnancy and breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to labetalol or any component; sinus bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; bronchial asthma; uncompensated cardiac failure; pregnancy (2nd and 3rd trimesters)

Use only with extreme caution in compensated heart failure and monitor for a worsening of the condition. Avoid abrupt discontinuation in patients with a history of CAD; slowly wean while monitoring for signs and symptoms of ischemia. Use caution with concurrent use of beta-blockers and either verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents. Patients with bronchospastic disease should not receive beta-blockers. Labetalol may be used with caution in patients with nonallergic bronchospasm (chronic bronchitis, emphysema). Use cautiously in diabetics because it can mask prominent hypoglycemic symptoms. Can mask signs of thyrotoxicosis. Can cause fetal harm when administered in pregnancy. Use cautiously in the hepatically impaired. Use caution when using I.V. labetalol and halothane concurrently (significant myocardial depression).

>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%), weakness (1%)

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: Increased transaminases (4%)

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

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

<1% (Limited to important or life-threatening symptoms): Hypotension, syncope, bradycardia, heart block, fever, diarrhea, drowsiness, increased sweating, 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, congestive heart failure, ventricular arrhythmias (I.V.)

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, ischemic colitis

Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia; atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol); CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs.

Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia and hypoglycemia; bradycardia and hypotension resistant to atropine, isoproterenol or pacing may respond to glucagon; wide QRS defects caused by the membrane-depressant poisoning may respond to hypertonic sodium bicarbonate; repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful in removal of only those beta-blockers with a small V_d, long half-life or low intrinsic clearance (acebutolol, atenolol, nadolol, sotalol)

CYP2D6 substrate/inhibitor

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

Cimetidine increases the bioavailability of labetalol.

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

NSAIDs may reduce antihypertensive efficacy of labetalol.

Sulfonylureas: Effects may be decreased by beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

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

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

Blocks alpha-, beta₁-, and beta₂-adrenergic receptor sites; elevated renins are reduced

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: Crosses placenta; small amounts in breast milk; moderately lipid soluble, therefore, can enter CNS

V_d: Adults: 3-16 L/kg; mean: <9.4 L/kg

Protein binding: 50%

Metabolism: Extensive first-pass effect; metabolized in liver primarily via glucuronide conjugation

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

Half-life, normal renal function: 2.5-8 hours

Elimination: <5% excreted in urine unchanged; possible decreased clearance in neonates/infants

Due to limited documentation of its use, labetalol should be initiated cautiously in pediatric patients with careful dosage adjustment and blood pressure monitoring.

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.

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.

Avoid natural licorice (causes sodium and water retention and increases potassium loss); food may increase bioavailability

Blood pressure, standing and sitting/supine, pulse, cardiac monitor and blood pressure monitor required for I.V. administration

False-positive urine catecholamines, VMA if measured by fluorometric or photometric methods; use HPLC or specific catecholamine radioenzymatic technique

Dizziness is common; may cause sedation

Barbiturates may decrease effects of beta-blockers; low potency antipsychotic and TCAs may potentiate the hypotensive effects of beta-blockers

Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia

Noncardioselective beta-blockers (ie, propranolol, nadolol) 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.

For I.V. use in emergency situations - patient information is included in general instruction. Oral: Take as directed, with meals. Do not skip dose or discontinue without consulting prescriber. Follow recommended diet and exercise program. Do not use alcohol or OTC medications which may affect blood pressure (eg, cough or cold remedies, diet pills, stay-awake medications) without consulting prescriber. If diabetic, monitor serum glucose closely and notify prescriber of changes; this medication can alter hypoglycemic requirements. You may experience drowsiness, dizziness, or impaired judgment (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from sitting or lying position or when climbing stairs); dry mouth, nausea, or loss of appetite (frequent mouth care or sucking lozenges may help); or sexual dysfunction (reversible, may resolve with continued use). Report altered CNS status (eg, fatigue, depression, numbness or tingling of fingers, toes, or skin); palpitations or slowed heartbeat; difficulty breathing; edema or cold extremities; or other persistent side effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Instruct patient regarding compliance; do not abruptly withdraw medication in patients with ischemic heart disease; IVP: Administer over 2-3 minutes

Injection, as hydrochloride: 5 mg/mL (20 mL, 40 mL, 60 mL)

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

A mixture of labetalol 40 mg/mL plus hydrochlorothiazide 5 mg/mL was found stable for 60 days in the refrigerator when prepared in a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or Ora-Sweet® SF and Ora-Plus®, and of cherry syrup

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