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Medication Safety Issues
Sound-alike/look-alike issues:
Labetalol may be confused with betaxolol, Hexadrol®, lamoTRIgine
Trandate® may be confused with traMADol, Trendar®, Trental®, Tridrate®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Significant differences exist between oral and I.V. dosing. Use caution when converting from one route of administration to another.
Pronunciation
(la BET a lole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of mild to severe hypertension; I.V. for hypertensive emergencies
Use: Unlabeled/Investigational
Pediatric hypertension
Pregnancy Risk Factor
C (manufacturer); D (2nd and 3rd trimesters - expert analysis)
Pregnancy Considerations
Labetalol crosses the placenta. Beta-blockers have been associated with persistent bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
Lactation
Enters breast milk/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Available evidence suggests safe use during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
Contraindications
Hypersensitivity to labetalol or any component of the formulation; 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)
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Orthostatic hypotension: May occur with I.V. administration; patient should remain supine during and for up to 3 hours after I.V. administration
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure (HF): Use with extreme caution in patients with compensated heart failure and monitor for a worsening of the condition.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease: Use with caution in patients with peripheral vascular disease (including Raynaud's).
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving anesthetic agents which decrease myocardial function.
• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
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 I.V. use, hypotension may occur in up to 58%
Central nervous system: Fatigue (1% to 10%), 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: Paresthesia (1% to 5%), 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.
Drug Interactions
Beta2-Agonists: Alpha-/Beta-Blockers may diminish the therapeutic effect of Beta2-Agonists. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Rituximab: Antihypertensives may enhance the hypotensive effect of Rituximab. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Alpha-/Beta-Blockers. Exceptions: Fluvoxamine. Risk C: Monitor therapy
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).
Storage
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) is 3 days.
Reconstitution
Standard diluent: 500 mg/250 mL D5W
Minimum volume: 250 mL D5W
Compatibility
Stable in D5LR, D51/4NS, D51/3NS, D5NS, D5W, LR, NS; incompatible with sodium bicarbonate 5% and alkaline solutions.
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
Blocks alpha-, beta1-, and beta2-adrenergic receptor sites; elevated renins are reduced. The ratios of alpha- to beta-blockade differ depending on the route of administration: 1:3 (oral) and 1:7 (I.V.).
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: Due to limited documentation of its use, labetalol should be initiated cautiously in pediatric patients with careful dosage adjustment and blood pressure monitoring.
Oral: Hypertension (unlabeled use): Initial: 1-3 mg/kg/day, in 2 divided doses; maximum: 10-12 mg/kg/day, up to 1200 mg/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 (acute loading): 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
Note: Although loading infusions are well described in the product labeling, the labeling is silent in specific clinical situations, such as in the patient who has an initial response to labetalol infusions but cannot be converted to an oral route for subsequent dosing. There is limited documentation of prolonged continuous infusions. In rare clinical situations, higher dosages (up to 6 mg/minute) have been used in the critical care setting (eg, aortic dissection). At the other extreme, continuous infusions at relatively low doses (2-6 mg/hour - note difference in units) have been used in some settings (following loading infusion in patients who are unable to be converted to oral regimens or in some cases as a continuation of outpatient oral regimens). These prolonged infusions should not be confused with loading infusions. Because of wide variation in the use of infusions, an awareness of institutional policies and practices is extremely important. Careful clarification of orders and specific infusion rates/units is required to avoid confusion. Due to the prolonged duration of action, careful monitoring should be extended for the duration of the infusion and for several hours after the infusion. Excessive administration may result in prolonged hypotension and/or bradycardia.
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Dosage adjustment in hepatic impairment: Dosage reduction may be necessary.
Administration: I.V.
Bolus administered over 2 minutes. Loading infusions (2 mg/minute) require close monitoring of heart rate and blood pressure and are usually terminated after response or cumulative dose of 300 mg. There is limited documentation of prolonged continuous infusions. In clinical experience, prolonged continuous infusions have been used. In rare clinical situations, higher dosages (up to 6 mg/minute) have been used in the critical care setting (eg, aortic dissection). At the other extreme, continuous infusions at relatively low doses (2-6 mg/hour: note difference in units) have been used in some settings (following loading infusion in patients who are unable to be converted to oral regimens or in some cases as a continuation of outpatient oral regimens). These prolonged infusions should not be confused with loading infusions. Because of wide variation in the use of infusions, an awareness of institutional policies and practices is extremely important. Careful clarification of orders and specific infusion rates/units is required to avoid confusion. Due to the prolonged duration of action, careful monitoring should be extended for the duration of the infusion and for several hours after the infusion. Excessive administration may result in prolonged hypotension and/or bradycardia.
Administration: I.V. Detail
Loading infusions (2 mg/minute) require close monitoring of heart rate and blood pressure and are terminated after response or cumulative dose of 300 mg. Continuous infusions of 2-6 mg/hour have been used in some settings and should not be confused with loading infusions.
pH: 3-4
Monitoring Parameters
Blood pressure, standing and sitting/supine, pulse, cardiac monitor and blood pressure monitor required for I.V. administration
Test Interactions
False-positive urine catecholamines, VMA if measured by fluorometric or photometric methods; use HPLC or specific catecholamine radioenzymatic technique
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as directed, with meals. Do not skip dose or discontinue without consulting prescriber. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. If you have diabetes, monitor serum glucose closely and notify prescriber of changes (this medication can alter glycemic response). 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; respiratory difficulty; edema or cold extremities; or other persistent side effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (ie, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response in the elderly than seen in younger adults. Despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (eg, exercise).
Cardiovascular Considerations
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists for another drug, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, postmyocardial infarction, high coronary disease risk, or diabetes. In type 2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Taste disorder.
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
Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia
Mental Health: Effects on Mental Status
Dizziness is common; may cause sedation
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease effects of beta-blockers; low potency antipsychotic and TCAs may potentiate the hypotensive effects of beta-blockers
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking (especially anything that will effect blood pressure). Blood pressure and heart rate should be assessed prior to and following first dose and any change in dosage. Caution patients with diabetes to monitor glucose levels closely; beta-blockers may alter glucose tolerance. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, CHF). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 5 mg/mL (4 mL, 8 mL, 20 mL, 40 mL)
Trandate®: 5 mg/mL (20 mL, 40 mL) [contains edetate disodium]
Tablet, as hydrochloride: 100 mg, 200 mg, 300 mg
Trandate®: 100 mg, 200 mg [contains sodium benzoate], 300 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Labetalol HCl)
100 mg (60): $20.99
200 mg (60): $28.99
300 mg (60): $38.99
Tablets (Trandate)
200 mg (60): $50.99
Extemporaneously Prepared
A 40 mg/mL suspension of labetalol hydrochloride can be made by first crushing sixteen 300 mg labetalol hydrochloride tablets into a fine powder. Using equal amounts of Ora-Sweet® and Ora-Plus® as a vehicle, add a small amount to make a paste; add additional amounts of the vehicle to qs to 120 mL. Suspension is stable for 60 days when stored in the refrigerator. Shake well before using.
Nahata MC and Hipple TF, Pediatric Drug Formulations, 4th ed, Cincinnati, OH: Harvey Whitney Books Co, 2000.
References
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Erstad BL and Barletta JF, “Treatment of Hypertension in the Perioperative Patient,” Ann Pharmacother, 2000, 34(1):66-79.
Lang DM, “Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers,” Drug Saf, 1995, 12(5):299-304.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114 (2 Suppl):555-76.
UK Prospective Diabetes Study Group, “Efficacy of Atenolol and Captopril in Reducing Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS 39,” BMJ, 1998, 317(7160):713-20.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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